",isbn:"978-1-83969-591-9",printIsbn:"978-1-83969-590-2",pdfIsbn:"978-1-83969-592-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"e39a567d9b6d2a45d0a1d927362c9005",bookSignature:"Dr. Umar Zakir Abdul Hamid and Associate Prof. Ahmad 'Athif Mohd Faudzi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10778.jpg",keywords:"Model-Based Control, Optimal Control, Industrial Automation, Linear Actuator, Nonlinear Actuator, System Identification, Soft Robotics, Service Robots, Unmanned Aerial Vehicle, Autonomous Vehicle, Process Engineering, Chemical Engineering",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 25th 2021",dateEndSecondStepPublish:"March 25th 2021",dateEndThirdStepPublish:"May 24th 2021",dateEndFourthStepPublish:"August 12th 2021",dateEndFifthStepPublish:"October 11th 2021",remainingDaysToSecondStep:"19 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Umar Zakir Abdul Hamid, Ph.D. is an autonomous vehicle expert, and with more than 30 scientific publications under his belt, Umar actively participates in global automotive standardization efforts and is a Secretary for a Society of Automotive Engineers (SAE) Committee.",coeditorOneBiosketch:"Associate Professor Dr. Ahmad 'Athif Mohd Faudzi has more than 100 scientific publications as of 2021 and is currently leading a team of 18 researchers in UTM doing research works on control, automation, and actuators.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"268173",title:"Dr.",name:"Umar Zakir Abdul",middleName:null,surname:"Hamid",slug:"umar-zakir-abdul-hamid",fullName:"Umar Zakir Abdul Hamid",profilePictureURL:"https://mts.intechopen.com/storage/users/268173/images/system/268173.jpg",biography:"Umar Zakir Abdul Hamid, PhD has been working in the autonomous vehicle field since 2014 with various teams in different countries (Malaysia, Singapore, Japan, Finland). 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1. Introduction
The term “preservation” may have different meanings depending on the field in which it is applied [1]. The knowledge of the preservation of artworks on different artifacts is not limited to historical and semiotic analyses. Preservation nowadays requires an interdisciplinary team with a solid knowledge of materials science, chemistry, physics, microbiology, art history and nanotechnology in order to contribute and offer solutions to prevent the natural aging of some artifacts (paper documents, stone, paints, etc.) and to provide useful and basic predictions about the degradation of the cultural patrimony and can come up with viable solutions [2, 3].
Generally speaking, the term “nano” defines an extremely small entity in the order of 10−9 m [4].
The applications of nanotechnologies in the field of preservation of cultural heritage could include:
Diagnosis of the damaged surfaces to obtain physicochemical and structural information on the materials that form the historic heritage and for identifying the surface damaging type: alveolarization, fractures and so on [5].
New instruments and diagnostic methods, in order to make an informed decision on the materials to use during the further phases of restoration [6].
Innovative methods for cleaning surfaces affected by polluting substances and black crusts [7].
Treatment of surfaces (protection, waterproofing, self-cleaning) [8].
New products for consolidation and protection of natural and artificial stones (compatible products) [9].
Materials and innovative processes against raising of humidity and against sulfation for the conservation and/or restoration interventions on art manufactures of different nature [10].
The present chapter means to complete a survey on the use of nanotechnology for the preservation and restoration of the stone monuments and different damaged paper and stone artifacts. The scientific principles behind numerous nanomaterials on different types of common movable and fixed artistic substrates are discussed. Compared to traditional methods, these new tools have the benefit of considerably less impact on both the operators and the environment. Different types of nanoparticles currently used to produce conservation treatments with enhanced material properties are discussed.
1.1. Nanomaterials for restoration and conservation of cultural heritage
Nanostructures represent a stage of matter between agglomerated molecules and structures and are typically characterized by a large surface area that affects their physicochemical properties. Innovative applications are of nanostructures and are based on two types of unique properties associated with nanostructures [11]:
New optical properties due to the generation of quantum effects.
Changes in reactivity and mechanical properties due to small physical dimensions and a large area of the specific surface. The advantages of small granule sizes in comparison with the agglomerated materials include: a low sintering temperature, super-elasticity, improved diffusion, improved dielectric and tribological properties.
One of the directions for the use of nanoparticles, nowadays, is the preservation of cultural heritage. The application of nanotechnologies to different artifacts has recently proved the huge potential of this science to apply in the field of preservation of universal cultural heritage [12, 13]. Solid nanodispersions, micelles, gels or microemulsions offer new viable solutions for the restoration and preservation of works of art. Some recently concerns are related to the synthesis and the application of nanoparticles of Ca and Mg or hydroxyapatite to paper and stone preservation [14]. In this chapter, the most used methods of nanoparticle synthesis and some of their recent applications for the preservation of artifacts are presented. The novelty of this area resides in a type of cultural heritage material (stone, paper) and starts with the main degradation paths and discussing protocols for the application of innovative nanomaterial-based tools for cleaning, consolidation or deacidification, which represent the majority of the case studies encountered in restoration and conservation procedures.
2. Artifacts conservation and restoration
2.1. Stone
2.1.1. Influence of pollutants
The main types of atmospheric pollutants which could affect the stony monuments are shown in Table 1.
Nr.crt.
Pollutant
Source
Effect on stone
1
Carbon dioxide and carbon monoxide
Internal combustion engines
Acid rain, soil pollution
2
Nitrogen and sulfur oxides
Combustion of fossil fuels by motor vehicles or thermoelectric power plants
Acid rain, soil pollution
3
Volatile organic compounds (hydrocarbons and hydrocarbon derivatives)
Combustion of fossil fuels, the evaporation of fuels, solvents used in various industrial processes
Acid rain, soil pollution
4
Suspended particulates—very small particles similar with gas may contain iron oxides,heavy metals (lead, cadmium, manganese,chromium), asbestos fibers or other pollutants
Combustion of fossil fuels, human activity
Acid rain, soil pollution
Table 1.
Pollutant source and effects on stone.
Usually, calcium carbonate can take three forms of polymorphs: calcite, aragonite and vaterite [15]. It is known that in the calcite variety (calcium carbonate variety detected by X-ray diffraction (XRD)) dissolution is affected by the presence of foreign substances Mg2+ (from MgSO4·7H2O, called epsomite), which is considered one of the major cations in seawater and groundwater. Also, SO42− (from atmospheric pollution responsible for calcite conversion in gypsum) and NO3 (responsible for solubilizing the stone in the wall) are the most damaging pollutants or different artifacts [16]. Processes such as crystallization and salt dissolution contribute to new pores, which are responsible for an accelerated damaging process through the microcracks generated in the stone. The dissolution rate significantly increases in the presence of NaCl solutions, due to electrostatic reasons. Calcium carbonate (CaCO3) can be found in soils, rocks and sediments. Among the minerals, calcium carbonate is one of the most sensitive ones to weathering [17]. Due to rapid weather destruction, small amounts of CaCO3 can dominate the geochemical behavior of aquatic systems. Given the sensitivity of this rock, it is necessary to study the influence of climatic and environmental factors on this rock [18].
The pollutant effects on buildings and monuments degradation require a multidisciplinary approach using conventional and unconventional methods to achieve a good understanding of the mechanisms and consequences of such pollution [6]. It has been established that the hydraulic properties of stones and their traction resistance are the most important parameters that control the stone resistance to decomposition, and these parameters are widely used to estimate their durability.
The effects of the environment on some monuments (Basarabi-Murfatlar Churches) have been assessed through various analytical investigations: thermal analysis, XRD, EDXRF and ion chromatography. When the temperature is less than 120°C, a weight loss due to the absorbed water is recorded, especially in the absence of hydrated salts. In the temperature range 200–600°C, a loss of chemically bonded water is registered, but no other compounds subjected to weight loss. After 600°C, CO2 loss is observed, due to the decomposition of carbonates, higher for the most degraded stones [19].
Stone surface alteration (determined by scanning electron microscopy (SEM) analysis coupled with diffused X-ray spectroscopy (SEM-EDX)) could be classified in several types:
Surface damage caused by sulfur and calcium and by the calcite reaction with the sulfur oxides present in the medium.
Alteration of the surface caused by deposits, when no chemical reactions occurred. These deposits are composed of dust from the anthropogenic particles. These degraded layers are mainly caused by the epigenetic formation of gypsum. In areas with high traffic, the sulfur oxide content is considerably higher [20]. There are two different mechanisms of destruction in the process of damaging the stones under the action of environmental conditions:
Chemical alteration of calcite and precipitation on gypsum that catches atmospheric particles on the surface.
Physical phenomenon of deposition of atmospheric particles on the surface.
Kruhl and Nega [21] investigated the fragmented form of quartz particles and found that the size of the fragments decreases as temperature increases during suture formation, while Bernal et al. [22] concluded that the processes of degradation cause the fragmentation of the surface size. Daniele and Taglieri [13] studied the morphology of quartz aggregates in granite and showed that the fragmented dimensions of the quartz aggregates are different depending on the type of granite. The sedimentary rocks are those originating:
Sedimentation and cementation under natural pressure of particles of natural rocks eroded by wind, rain, sunbathing, conglomerate and sandstone.
Precipitation from natural solutions—gypsum, limestone, dolomite and travertine; sedimentation and consolidation of residues of dead organisms (shells, shells)—diatomite, limestone and chalk. The limestone is derived from marine sediments and fossilized organic lakes (such as crinoids or brachiopods), consisting of calcium carbonate or calcite. Sandstones are the result of sedimentation of sand together with silica or calcium carbonate; the silica in the tiles may have the same adverse effect encountered at the granite. Both sedimentary rocks—limestone and sandstone—are easier to cut than granite, which has made them quite often used in the masonry of historical buildings [23, 24]. On the Romanian territory, there are many masonry made of siliceous sandstone or calcareous sandstone, the first being those with higher compressive strength. The mineralogical composition and crystal structure of the stone monuments before and after the conservation treatment can be determined by X-ray diffraction (XRD) [25, 26]. A sample of CaCO3 (Figure 1) has a series of diffraction peaks at 2ϑ: 29.5, 39.5, 47.6, 48.58, etc., corresponding to the calcite phase, which shows that in the water the precipitated calcium carbonate crystals were formed mainly of calcite.
Figure 1.
X-ray diffraction of calcite.
In Figure 2, there are Fourier transform infrared (FTIR) peaks corresponding to the vaterite phase generated inside and outside of the damaged limestone surfaces.
Figure 2.
FTIR spectra of inside and outside treated limestone surface.
Very clear bands could be observed in FTIR spectra, which show significant differences between not-treated and treated limestones, especially at the bands assigned to carbonate groups and to sulfate bands (Figure 3).
Figure 3.
FTIR spectra of not-treated and treated limestones.
2.2. Causes of natural stone degradation
The natural stone is subjected to a slow and continuous process of deterioration (known as alteration— or degradation, or even “decay”), which is a phenomenon caused by physicochemical causes other than mechanical actions: moisture; crystallization of salts in the mass of the material; deposition of pollutants on the surface of the rock, acting through chemical and/or biological processes; high temperature variations during day and night (strong heat cycles - temperature drop) or accidental fire action; and erosion due to strong winds (process without significant mechanical stress) [25, 26, 27].
Moisture is one of the main factors that attack stones through the capillary phenomenon, and limestone, dolomite and marble are most affected by this external factor [28]. During 10 years of exposure to a 100 cm column of atmospheric precipitation, calcareous rocks can reduce their thickness by 0.2 mm. Moisture can also affect the rocks that contain the tiny black, feldspar and tremolite. In the case of granite, the moisture from the pores can lead to the splitting of the stone into layers of 1–3 mm thick, through the expansion-contraction cycles (important to the reversible frost-thaw phenomena, because the freezing volume increases with 9%).
Salt crystallization is one of the main phenomena of the destruction of porous materials, which occurs by penetrating the material pores by the aqueous solution containing dissolved pollutants, such as mineral salts, combustion gases, powdered plant residues and microorganisms, Table 2. The tensions in the surfaces that delineate the pores due to the salts crystallized here, known as “stone efflorescence,” represents a great danger for the durability of a historical structure. The most common salts in the efflorescence phenomenon of masonry are sulfates, carbonates and nitrates (sodium, magnesium, calcium, potassium), generated from the atmospheric pollutants (SO2, NO2 and CO2), which are transformed in (HNO3, H2SO4 and H2CO3) in contact with the mortars [24, 29].
Nr.crt.
Factor
Source
Effect on stone
1
Moisture
Rain, freeze-thaw cycles, groundwater,
Construction, surface water mitigating through the shoulder, ditches or imbibing through in the paved surface of the pavement
2
Salt crystallization
Mirabilite (Na2SO4• 10H2O) and thenardite (Na2SO4)
Severe alveolar weathering, granular disintegration, efflorescences and subflorescences in buildings, monuments and quarry
3
Freeze-thaw cycles
Weather seasons
Severe alveolar weathering, granular disintegration, efflorescences and subflorescences in buildings, monuments and quarry
4
Black crusts - soiling on buildings. This aids the production of gypsum, which crystallizes on the surface
Exposition to moisture in the form of fog, mist or dew. Diesel engines are one of the most damaging particle sources
Ongoing decay mechanisms, such as salt weathering
Table 2.
Causes of natural stone degradation.
Freeze-thaw cycles. If the mortar pores are filled with water, a pressure will be exerted on the pore walls of the mortar due to the increase in the volume (by 9%) of the frozen water. Thus, prolonged freeze-thaw cycles will progressively degrade mortars with moisture. The most sensitive to this phenomenon is lime mortars [30].
2.3. Type of inorganic nano-consolidants
The nanomaterials are adequate materials for the architectural heritage, due to their consolidation and protection capacity of damaged building materials. The nanoparticles are able of self-cleaning coatings for a preventive protection system for historical surfaces, preserving the original aspect of treated elements, decreasing the deposition of pollutants and soiling and reducing the onset of external degradation processes due to soiling phenomena. The nanoparticles must have the following attributes: termal stability, biologically and chemically inertness, nontoxic, low cost, stable toward visible or near UV light, good adaptability to various environment and good adsorption in solar spectrum. In addition, these treatments can also have water repellent properties, which favor this self-cleaning action. On the other hand, the presence of soluble salts is recognized as an important decay agent of stone heritage. Thus, in the last few years, the study of the application of nanoparticles as a desulfating agent for stone, mortars and wall paintings is being carried out [31].
The principle of the inorganic materials is to create an insoluble “paste” that fills the pores of the stone. There is a large area of such consolidants, as it is shown in Table 3.
Nr.crt.
Consolidant
Effect
1
Alcalo-silicates
Deposition of silica in the limestone mass
2
Silico-fluoride
Silicone tiles can form a cemented crust on the outside, a layer of higher hardness. In general, these solutions are no longer recommended
3
Alkaline hydroxides
The consolidation effect is still low, requiring repeat treatment to make it more effective. The process remains relatively uneconomical
4
Strontium and barium hydroxides
These solutions seem to be more effective than calcium-based, but experts believe the problem of the durability of the treated stone, the application to historical structures
5
Inorganic builders (zinc stearate and aluminum stearate, aluminum sulfate, phosphoric acid, phosphate and hydrofluoric acid )
Superficial penetration into the pores of the stone. Danger of microorganism population
6
Alcosilanes (or alkoxylans). Increased mechanical strength has also been reported with approx. 20% of the silicon tiles treated, which is already performing
The best materials with a reinforcing function A deep penetration into the pores of silky tiles. The penetration of the alkoxylans in the stone occurs at a depth of 20–25 mm, which means much more than the inorganic builders
7
Acrylic polymers (methyl-methacrylate, methyl-acrylate, ethyl-methacrylate and butyl-methacrylate).
All of these builders have increased the resistance of the treated stone layer, but unfortunately they are unstable in color under the action of the already mentioned agents
Polyvinyl acetate may cause a glossy-glassy appearance on the surface of the stone. On the other hand, if the polymers were insufficiently diluted in the solvent, layers were formed which could represent a screen for retaining the moisture and salts in the stone, that is, exactly the opposite of what was intended by applying the waterproofing treatment
9
The polyurethanes
Treatment is very effective, but warmth and light produce opposite effects
Table 3.
Consolidants used for stone and their effects.
Some inorganic materials, such as calcium hydroxide Ca(OH)2, magnesium hydroxide Mg(OH)2, barium hydroxide Ba(OH)2, strontium hydroxide Sr(OH)2 and hydroxyapatite (HAp), have already been used as consolidants for different damaged carbonate stones [32]. Calcium hydroxide has been used as nanoparticles (130–300 nm), dispersed in alcohols, as nanosols (50–250 nm), as “pastelike” in ethanol and as calcium hydroxide microparticles (1–3 mm) [33]. But, due to their low porosity, high moisture content of the substrate, oversaturation of the material and quick evaporation of the solvent, calcium hydroxide is not an optimal option for this monument [34]. This is the reason for finding other optimal materials. Also, a reduced penetration depth and a limited solubility of lime in water are causing chromatic alteration of stone surface [35, 36]. Except the metallic hydroxides above mentioned, for stone consolidation could be used hydroxyapatite (HAp) [37, 38]. It is a natural mineral form of calcium apatite having the formula Ca10(PO4)6(OH)2 and has the ability to readily accept in its structure numerous substitution ions for both Ca2+ and PO43 ions, with the chemical composition altering and the morphological structure [39]. The OH− ion may be replaced by fluoride, chloride or carbonate ions, producing fluorouracil or chlorapatite [40].
3. Paper
3.1. Considerations on the methods of conserving the historical paper
Hydrolysis of acid-catalyzed cellulose is the main source of paper degradation. It is well known that the degradation process resides in the manufacture of low quality paper. At the beginning of the eighteenth century, papermaking technology changed and the paper began to be made of increasingly reactive materials (wood pulp) and acidic substances (rosin, used for sizing, chlorine for bleaching and so on). After a long period of exposure to environmental conditions (e.g., temperature, humidity, light), these substances accelerate chemical degradation of the paper. The global effect is the rapid decrease in the resistance to degradation of paper documents, especially on paper made since the eighteenth century [41, 42, 43]. There is a general consensus on the inevitable treatment of deacidification in paper preservation. Deacidification involves a complete neutralization of the paper and, in most cases, the introduction of an alkaline reservoir that opposes the acidity assault in the environment (e.g., pollution) [44]. In this context, many studies have been developed addressing acidity elimination processes [45]. The best methods of deacidification are based on nonaqueous solvents. Less polar fluids minimize the risk of ink solubility. Among these most important deacidification methods are the Wei T\'o method and the Bookkeeper method [46].
Recently, a new method has been proposed based on alcohols dispersed in calcium hydroxide nanoparticles that give good results in deacidification of the paper. The above-mentioned studies have also been extended to the treatment of paper with magnesium hydroxide nanoparticles (brucellosis) because it has been shown that magnesium reduces the rate of oxidative degradation of the cellulose substrate due to exposure to light.
Magnesium hydroxide nanoparticles, Mg(OH)2 (brucite), can be obtained by hydrating Mg (MgO), precipitating magnesium salts with an alkaline solution and electrolyzing an aqueous solution of a bounce magnesium.
Mg(OH)2 is usually accomplished by the first two methods [47]. When magnesium hydroxide powder is used as a precursor for the synthesis of magnesium oxide, the size of the hydroxide particles, the shape and degree of agglomeration of these are key parameters for many applications. An example is the sintering stage in the ceramic manufacturing process. Magnesium-based alkaline compounds are of great importance in the preservation of cultural heritage. Such an area of interest is also the treatments for deacidification of acidic paper in order to preserve it. Both the Wei T\'o and Bookkeeper methods are based on the use of magnesium compounds that generate Mg(OH)2 “in situ” after hydrolysis. Unfortunately, some studies have demonstrated a limited homogeneous distribution of alkaline reservoirs [48]. The purpose of the new studies was to synthesize magnesium nanoparticles following the procedure similar to that of calcium hydroxide, which yielded very good results. Unlike the Wei T\'o and Bookkeeper methods, these nanoparticles once deposited on the paper immediately acquire the role of deacidifier or buffer. Synthetic pathways for Mg(OH)2 nanoparticles have an important role both theoretically and practically. Several papers have shown that the precipitation of metallic hydroxides in their salts is strongly affected by variation in synthesis parameters. These include high-temperature reactions, reagent concentration and aging time. In particular, it was demonstrated that temperatures above 100°C promote the formation of nanoparticles in nonaqueous media. Some studies also reported significant effects of organic solvents related to the shape and size of precipitated particles. The obtained particles were characterized for determination of their chemical nature by: FT-TR spectroscopy, specific surface area (SA) measurement of dry powder, X-ray diffraction (XRD) characterization and shape and size characterization by SEM and TEM electronic microscopy with scanning or electron transmission. Applying deacidification of nanoparticle paper is compared to Wei T\'o [49].
In some cases, during the degradation process, it is possible to identify some odorous compounds such as vanillin or vanilic acid, well identified by gas chromatography, Figure 4.
Figure 4.
GC-MS chromatogram of the damaged paper.
3.1.1. Synthesis of nanoparticles of alkaline hydroxides
This process can be considerably stopped or slowed down by deacidification treatment. The excellent deacidification agents are Mg(OH)2 and Ca(OH)2 because they provide very good physicochemical compatibility with the support, and after conversion into carbonates, they work as alkaline reservoirs without producing any undesirable side effect [50].
Nanoparticles dispersed in alcohols can be applied to the paper by spraying, impregnating or dipping [51]. This method produces in situ hydroxides and requires dispersants to stabilize the system. The solvents used are volatile, environmentally friendly and with low surface tension so that they act as carrier solids for solid particles and ensure the homogeneity and penetration of nanoparticles into the depth of cellulose fibers [52].
The synthesis of Ca(OH)2 and Mg(OH)2 nanoparticles was made in heterogeneous medium, and CaO and MgO reagents were used. The oxides in turn were obtained from the corresponding carbonates, which were initially milled and then milled to a size of 100 μm. Then, the carbonates were calcined at 1000°C. Both carbonates were of analytical purity.
The process consists of suspending in a mixture of isopropyl alcohol and water in each of the two stoichiometric proportions of the respective oxides according to the equations given above. The hydrolysis reaction was carried out at 80°C for about 30 min (using deionized water).
3.1.2. Treatment of paper document with suspension of alkaline hydroxide nanoparticles
The resulting particles were used to treat paper with HAp in isopropanol, and the historical paper was manually sprayed. The pulverized sheets were from a book printed in Romania, in Bucharest, from a private collection from the end of the nineteenth century. Untreated paper was taken as a reference. The paper was then treated with the nanoparticles of Ca(OH)2 or Mg(OH)2 and examined by scanning electron microscopy (SEM) [37, 38]. Initially untreated, unwritten, unprinted and uncolored paper was investigated by SEM and AFM, too, as a reference (Figure 5).
Figure 5.
SEM images for not-damaged and damaged cellulose substrates.
The cellular microarchitecture of cellulose was investigated by SEM. The micrographs obtained for this sample revealed a densely packed cellulose fiber network which, on a microscopic scale, inside the sheet of paper appears randomly oriented without having a majority direction of microfiber orientation. The fibers are homogeneous and seem to come from plant fibers, perhaps cotton or linen. The size of the fibers is different, some of them are whole, others are broken. Some fibers have inlay that might be salt crystals. The presence of mineral crystals in paper can be considered as a consequence of how it is made (Figure 6). The presence of luminous areas on the image is a consequence of either the presence of a thicker part of the glue material or a rupture of the paper [53].
Figure 6.
AFM images of not-damaged and damaged cellulose substrates.
On a macroscopic examination of the sprayed sample of nanoparticles of Mg(OH)2, no negative influence on the optical parameters of the paper is observed. Some white deposits of Mg (OH)2 were formed on the paper surface more pronounced in this case than in the case of Ca (OH)2, although both consolidants have the same concentration and volume applied to the same type of paper. Not all Mg (OH)2 nanoparticles neutralize the acidity of the paper and the unreacted quantity will be carbonated over time in the presence of atmospheric CO2.
3.1.3. Hydroxyapatite nanoparticles: synthesis and characterization
Hydroxyapatite (HAp) was obtained by the modified precipitation chemical method, and the synthesized substance was analyzed by spectral techniques: atomic force microscopy (AFM), scanning electron microscopy (SEM) (Figure 7) X-ray diffraction (XRD) and spectroscopy in Fourier transform infrared (FTIR).
Figure 7.
SEM images of not-treated and treated papers with Hap.
As synthesis reagents were used, calcium nitrate tetrahydrate, Ca(NO3)2·4H2O, and dibasic ammonium phosphate, (NH4)2HPO4, were previously dissolved each in deionized water. Then, the solution of Ca(NO3)2·4H2O was added dropwise over the (NH4)2HPO4 solution, which was stirred vigorously at room temperature for about 1 h until a milky and somewhat gelatinous precipitate was obtained and further stirred for further 1 h to increase the reaction rate and homogenize the mixture [20]. The mixture was synthesized at 100°C for 24 h. Then, the precipitate was washed and filtered on a glass filter. After filtration, the compact and sticky cake was dried at 80°C in a furnace. The dried powder was then ground into a mortar and then calcined in an alumina crucible for 4 h [27].
As a method of synthesis, a modified wet precipitation method has been chosen because this is more advantageous due to the ease with which it is achieved, the low working temperature, the relatively important percentage of the pure product and the synthesis equipment that is not expensive. It has been found that well-crystallized products with a low degree of sintering have been obtained, but relatively high calcination temperatures were required and the application of this long-term treatment, 4 h, was to obtain a finished product with the desired parameters [3]. Both X-ray diffraction and infrared spectroscopy showed the high degree of purity of the reaction products [54]. The study of SEM and AFM images was very consistent with the results obtained by other analysis techniques: thermal analysis [46]. It has been determined that the crystal size for HAp synthesized is 70–nm. It has also been concluded that a sintering temperature of the synthesis product above 850°C leads to the occurrence of a by-product reaction, namely tricalcium phosphate, and for its conversion into Hap, it is necessary to calcinate at 1200°C for 4 h.
4. Conclusions
Nanomaterials bring huge enhancements of improvement endeavors for various applications, due to the extensive scale nanomaterials for auxiliary applications. The structure-handling property acquires an imperative segment in the cultural heritage. The present paper plans to do a review of the condition of workmanship on the use of some nanomaterials to the preservation and rebuilding of the stony and paper cultural artifacts. With a smaller size, a higher penetrability, viscosity, thermal and magnetic properties, in comparison with the traditional materials, the nanomaterials can contribute to solve the problems deriving from specific phenomena that could appear during the intervention and to identify the potential newly formed products in the treated materials. In this chapter, some aspects about the nanomaterials used for conservation and restoration of stone and paper artifacts are evidenced and discussed. Distinctive sorts of nanoparticles right now used to create preservation with upgraded material properties and novel functionalities have been discussed and exemplified in this chapter (Ca(OH)2, Mg(OH)2, Ba(OH)2, Sr(OH)2, hydroxyapatite), both for their synthesis, characterization and specific applications for paper and stone surfaces.
Acknowledgments
This chapter received financial support from MCI-UEFISCDI by the projects: PNII 261/2014, PN 16.31.02.04.04, 11 BM/2016 and 31CI/2017.
\n',keywords:"nanomaterial, nanotechnology, cultural heritage, hydroxyapatite",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/57951.pdf",chapterXML:"https://mts.intechopen.com/source/xml/57951.xml",downloadPdfUrl:"/chapter/pdf-download/57951",previewPdfUrl:"/chapter/pdf-preview/57951",totalDownloads:662,totalViews:275,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,dateSubmitted:"July 9th 2017",dateReviewed:"October 25th 2017",datePrePublished:"December 20th 2017",datePublished:"April 18th 2018",dateFinished:null,readingETA:"0",abstract:"This chapter aims to evaluate the nanomaterials that can be used to diagnostic, conservation and restoration of different artifacts and monuments and that can contribute to solving the problems which could appear during weathering processes of them. The nanotechnology, as a new and revolutionary area in science, can improve the traditional methods currently used for restoration and preservation in cultural heritage and can contribute to the creation of new highly specialized methods for diagnostic and treatment of different artifacts or even monuments. With a smaller size, a higher penetrability, viscosity, thermal and magnetic properties, in comparison with the traditional materials, the nanomaterials can contribute to solve the problems deriving from specific phenomena that could appear during the intervention and to identify the potential newly formed products in the treated materials. In this chapter, some aspects about the nanomaterials used for conservation and restoration of stone and paper artifacts are evidenced and discussed.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/57951",risUrl:"/chapter/ris/57951",book:{slug:"novel-nanomaterials-synthesis-and-applications"},signatures:"Rodica-Mariana Ion, Sanda-Maria Doncea and Daniela Ţurcanu-\nCaruțiu",authors:[{id:"171504",title:"Prof.",name:"Rodica-Mariana",middleName:null,surname:"Ion",fullName:"Rodica-Mariana Ion",slug:"rodica-mariana-ion",email:"rodica_ion2000@yahoo.co.uk",position:null,institution:{name:"Valahia University of Targoviste",institutionURL:null,country:{name:"Romania"}}},{id:"176482",title:"Prof.",name:"Daniela",middleName:null,surname:"Turcanu-Carutiu",fullName:"Daniela Turcanu-Carutiu",slug:"daniela-turcanu-carutiu",email:"d_turcanu2002@yahoo.com",position:null,institution:{name:"Ovidius University",institutionURL:null,country:{name:"Romania"}}},{id:"225658",title:"Dr.",name:"Sanda Maria",middleName:null,surname:"Doncea",fullName:"Sanda Maria Doncea",slug:"sanda-maria-doncea",email:"sandamariadoncea@yahoo.com",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1. Nanomaterials for restoration and conservation of cultural heritage",level:"2"},{id:"sec_3",title:"2. Artifacts conservation and restoration",level:"1"},{id:"sec_3_2",title:"2.1. Stone",level:"2"},{id:"sec_3_3",title:"Table 1.",level:"3"},{id:"sec_5_2",title:"2.2. Causes of natural stone degradation",level:"2"},{id:"sec_6_2",title:"2.3. Type of inorganic nano-consolidants",level:"2"},{id:"sec_8",title:"3. Paper",level:"1"},{id:"sec_8_2",title:"3.1. Considerations on the methods of conserving the historical paper",level:"2"},{id:"sec_8_3",title:"3.1.1. Synthesis of nanoparticles of alkaline hydroxides",level:"3"},{id:"sec_9_3",title:"3.1.2. Treatment of paper document with suspension of alkaline hydroxide nanoparticles",level:"3"},{id:"sec_10_3",title:"3.1.3. Hydroxyapatite nanoparticles: synthesis and characterization",level:"3"},{id:"sec_13",title:"4. Conclusions",level:"1"},{id:"sec_14",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Preservation Technologies PTLP. Preservation Technologies PTLP [Internet]. 15 January 2000 [Updated: 15 January 2000]. Available from: http://ptlp.com/base.html [Accessed: 07 October 2017]'},{id:"B2",body:'Colangiuli, D; Calia, A; Bianco, N. Novel multifunctional coatings with photocatalytic and hydrophobic properties for the preservation of the stone building heritage. Construction and Building Materials. 2015;93189-196. DOI: http://dx.doi.org/10.1016/j.conbuildmat.2015.05.100'},{id:"B3",body:'Dei, L., Salvadori, B. Nanotechnology in cultural heritage conservation: nanometric slaked lime saves architectonic and artistic surfaces from decay. Journal of Cultural Heritage. 2006;7(2):110-115. DOI: http://dx.doi.org/10.1016/j.culher.2006.02.001'},{id:"B4",body:'Hensen E, Doehne E, Fidler J, Larson J, Martin B, Matteini M, Rodríguez-Navarro C, Sebastian Pardo E, Price C, de Tagle A, Teutonico J-M, Weiss NR. A review of selected inorganic consolidants and protective treatments for porous calcareous materials. Reviews in Conservation. 2003;4(13-25). DOI: http://dx.doi.org/10.1179/sic.2003.48.Supplement-1.13'},{id:"B5",body:'Álvarez de Buergo M, Fort R. A basic methodology for evaluating and selecting water-proofing treatments applied to carbonatic materials. Progress in Organic Coatings. 2001;43:258-266'},{id:"B6",body:'López-Arce P, Gomez-Villalba LS, Fernández-Valle ME, Álvarez de Buergo M, Fort R.Influence of porosity and relative humidity on consolidation of dolostone with calcium hydroxide nanoparticles: Effectiveness assessment with non-destructive techniques. Materials Characterization. 2010;61(2):168-184'},{id:"B7",body:'Vázquez-Calvo C, Ávarez de Buergo M, Fort R, Varas-Muriel MJ. Characterization of patinas by means of microscopic techniques. Materials Characterization. 2007;58(11-12):1119-1132. DOI: http://dx.doi.org/10.1016/j.matchar.2007.04.024'},{id:"B8",body:'Daniele V, Taglieri G, Quaresima R. The nanolimes in cultural heritage conservation: Characterisation and analysis of the carbonatation process. Journal of Cultural Heritage. 2008;9(3):294-301. DOI: http://dx.doi.org/10.1016/j.culher.2007.10.007'},{id:"B9",body:'Ferreira Pinto AP, Delgado-Rodrigues J. Stone consolidation: The role of treatment procedures. Journal of Cultural Heritage. 2008;9(1):38-53. http://dx.doi.org/10.1016/j.culher.2007.06.004'},{id:"B10",body:'Naidu S, Sassoni E, Scherer GW. New treatment for corrosion-resistant coatings for marble and consolidation of limestone. In: Stefanaggi M, Vergès-Belmin V. Eds, Jardins de Pierres – Conservation of Stone in Parks, Gardens and Cemeteries, Paris, 22-24 June 2011. pp. 289-294; 2011. ISBN: 2-905430-17-6'},{id:"B11",body:'Ion RM. Nano Crystalline Materials. Bucharest: FMR Ed; 2003. 189 p'},{id:"B12",body:'Baglioni P, Chelazzi D, Giorgi R. Nanotechnologies in the conservation of cultural heritage. A compendium of materials and techniques. Edit. Springer; 2015. ISBN: 978-94-017-9303-2'},{id:"B13",body:'Daniele V, Taglieri G. Nanolime suspensions applied on natural lithotypes: The influence of concentration and residual water content on carbonatation process and on treatment effectiveness. Journal of Cultural Heritage. 2010;11(1):102-106'},{id:"B14",body:'Ion RM, Teodorescu S, Ştirbescu RM, Dulamă ID, Şuică-Bunghez IR, Bucurică IA, Fierăscu RC, Fierascu I, Ion ML. Effects of the restoration mortar on chalk stone buildings. IOP Conference Series: Materials Science and Engineering; 2016; Jessy. 2016:012038'},{id:"B15",body:'Lopez-Arce P, Zornoza-Indart A. Carbonation acceleration of calcium hydroxide nanoparticles: induced by yeast fermentation. Applied Physics A. 2015;120(4):1475-1495'},{id:"B16",body:'Ion RM, Fierascu RC, Leahu M, Ion ML, Turcanu D. Nanomaterials for conservation and preservation of historical monuments. In: Proc EWCHP; Bolzano. 2013. pp. 97-104'},{id:"B17",body:'Ion RM, Bunghez RI, Pop SF, Fierascu RC, Ion ML, Leahu M. Chemical weathering of chalk stone materials from Basarabi churches. Metalurgia International. 2013;18(1):89-93'},{id:"B18",body:'López-Arce P, Gomez-Villalba LS, Martínez-Ramírez S, Álvarez de Buergo M, Fort R. Influence of relative humidity on the carbonation of calcium hydroxide nanoparticles and the formation of calcium carbonate polymorphs. Powder Technology. 2011;205(1):263-269. DOI: http://dx.doi.org/10.1016/j.powtec.2010.09.026'},{id:"B19",body:'Ion RM, Ion ML, Radu A, Şuică-Bunghez RI, Fierăscu RC, Fierăscu I, Teodorescu S. Mortar pe bază de nanomateriale pentru conservarea faţadelor construcţiilor. Romanian Journal of Materials. 2016;46(4):412-416'},{id:"B20",body:'Ion RM, Bunghez IR, Teodorescu S, Ion ML. Degradation of chalk stones induced by freeze–thaw action. In: Proc. XIX-th international conference “INVENTICA 2015”; June 2015; Jessy. Jessy: Performantica. 2015. pp. 141-147'},{id:"B21",body:'Kruhl JH, Nega M. The fractal shape of sutured quartz grain boundaries: application as a geothermometer. Geologische Rundschau. 1996;85(1):38-43'},{id:"B22",body:'Bernal SA, Mejía de Gutiérrez R, Provis JL. Engineering and durability properties of concretes based on alkali-activated granulated blast furnace slag/metakaolin blends. Construction and Building Materials. 2012;33:99-108'},{id:"B23",body:'Campbell A, Hamilton A, Stratford T, Modestou S, Ioannou I. Calcium hydroxide nanoparticles for limestone conservation: Imbibition and adhesion. Proceedings of Symposium, Adhesives and Consolidants for Conservation, Ottawa. 2011:1-16'},{id:"B24",body:'Drdácký M, Slížková Z, Ziegenbalg G. A nano approach to consolidation of degraded historic lime mortars. Journal of Nano Research. 2009;8:13-22. DOI: http://dx.doi.org/10.4028/www.scientific.net/JNanoR.8.13'},{id:"B25",body:'Ruffolo S, LaRussa MF, Aloise P, Belfiore CM, Macchia A, Pezzino A, Crisci GM. Efficacy of nanolime in restoration procedures of salt weathered limestone rock. Applied Physics A: Materials Science and Processing. 2014;114:753-758'},{id:"B26",body:'Slíížková Z, Drdácký M, Viani A. Consolidation of weak lime mortars by means of saturated solution of calcium hydroxide or barium hydroxide. Journal of Cultural Heritage. 2015;16:452-460. http://dx.doi.org/10.1016/j.culher.2014.09.003'},{id:"B27",body:'Ambrosi M, Ambrosi M, Dei L, Giorgi R, Neto C, Baglioni P. Colloidal particles of Ca(OH)2: Properties and applications to restoration of frescoes. Langmuir. 2001;17(14):4251-4255'},{id:"B28",body:'Kryza R, Prell M, Czechowski F, Domaradzka M. Acidic weathering of carbonate building stones: experimental assessment (preliminary results). Studia Universitatis Babeş-Bolyai. Geologia. 2009;54(1):33-36'},{id:"B29",body:'Sassoni E, Franzoni E. Sugaring marble in the Monumental Cemetery in Bologna (Italy): characterization of naturally and artificially weathered samples and first results of consolidation by hydroxyapatite. Applied Physics A. 2014;117:1893-1906. http://dx.doi.org/10.1007/s00339-014-8629-3'},{id:"B30",body:'Winkler EM. Stone: Properties, Durability in Men’s Environment. Wien: Springer Verlag; 1973. p. 223'},{id:"B31",body:'Hansen E, Doehne E, Fidler J, Larson J, Martin B, Matteini M, et al. A review of selected inorganic consolidants and protective treatments for porous calcareous materials. Reviews in Conservation. 2003;4:13-25. http://dx.doi.org/10.1179/sic.2003.48.Supplement-1.13'},{id:"B32",body:'Pianski J, Brümmer K, Ziegenbalg G.. Nano-particles for stone conservation-state of the art, characteristics and recent developments. In: Stonecore—“Recent Progress in the Consolidation of Calcareous Materials”, Litomysl, Czech Republic, 21-22 April 2010; 2010'},{id:"B33",body:'Daniele V, Taglieri G. Ca(OH)2 nanoparticle characterization: microscopic investigation of their application on natural stones. Materials Characterisation. 2011;72:55-66'},{id:"B34",body:'Giorgi R, Ambrosi M, Toccafondi N, Baglioni P. Nanoparticles for cultural heritage conservation: Calcium and barium hydroxide nanoparticles for wall painting consolidation. Chemistry - A European Journal. 2010;16(31):9374-9382'},{id:"B35",body:'Delgado Rodrigues J, Ferreira Pinto AP. Laboratory and onsite study of barium hydroxide as a consolidant for high porosity limestones. Journal of Cultural Heritage. 2016;19:467-476. http://dx.doi.org/10.1016/j.culher.2015.10.002'},{id:"B36",body:'Ciliberto E, Condorelli GG, La Delfa S, Viscuso E. Nanoparticles of Sr(OH)2: synthesis in homogeneous phase at low temperature and application for cultural heritage artefacts. Applied Physics A-Materials Science Process. 2008;91(1):137-141. http://dx.doi.org/10.1007/s00339-008-4464-8'},{id:"B37",body:'Sassoni E, Naidu S, Scherer GW. The use of hydroxyapatite as a new inorganic consolidant for damaged carbonate stones. Journal of Cultural Heritage. 2011;12:346-355. http://dx.doi.org/10.1016/j.culher.2011.02.005'},{id:"B38",body:'Ion R-M, Turcanu-Carutiu D, Fierascu R-C, Fierascu I. Chalk Stone restoration with hydroxyapatite-based nanoparticles. SBMM. 2014;12:9:24'},{id:"B39",body:'Ion R-M, Turcanu-Carutiu D, Fierascu R-C, Fierascu I, Bunghez I-R, Ion M-L, Teodorescu S,Vasilievici G, Raditoiu V. Caoxite-hydroxyapatite composition as consolidating material for the chalk stone from Basarabi-Murfatlar churches ensemble. Applied Surface Science. 2015;358:612-618. http://dx.doi.org/10.1016/j.apsusc.2015.08.196'},{id:"B40",body:'Ion RM, Fierascu RC, Fierascu I, Senin RM, Ion ML, Leahu M. Influence of Fântâniṭa Lake (Chalk Lake) Water on the Degradation of Basarabi–Murfatlar Churches. Engineering Geology for Society and Territory. 2015;8:543-546'},{id:"B41",body:'Sequeira S, Casanova C, Cabrita EJ. Deacidification of paper using dispersions of Ca(OH)2 nanoparticles in isopropanol. Journal Cultural Heritage. 2006;7:264-272'},{id:"B42",body:'Ion R-M, Doncea SM, Ion M-L, Rǎdiţoiu V, Amǎriuţei V. Surface investigations of old book paper treated with hydroxyapatite nanoparticles. Applied Surface Science. 2013;285(A):27-32'},{id:"B43",body:'Taglieri G, Daniele V, Del Re G, Volpe R. A new and original method to produce Ca(OH)2 nanoparticles by using an anion exchange resin. Advances in Nanoparticles. 2015;4:17-24. DOI: 10.4236/anp.2015.42003'},{id:"B44",body:'Roy A, Bhattacharya J. Synthesis of Ca(OH)2 nanoparticles by wet chemical method. Micro & Nano letters. 2010;3:131-134'},{id:"B45",body:'Samanta A. Synthesis of nano calcium hydroxide in aqueous medium. Journal American Ceramic Society. 2016;795:787-795'},{id:"B46",body:'Doncea SM, Ion RM, Fierascu RC, Bacalum E, Bunaciu AA, Aboul-Enein HY. Spectral methods for historical paper analysis: Composition and age approximation. Instrumentation Science and Technology. 2010;38(1):96-106'},{id:"B47",body:'Gomez-Villalba LS, López-Arce P, de Buergo MA, Zornoza-Indart A, Fort R. Mineralogical and textural considerations in the assessment of aesthetic changes in dolostones by effect of treatments with Ca(OH)2 nanoparticles. Science and Technology for the Conservation of Cultural Heritage. 2013;235-329'},{id:"B48",body:'Doncea SM, Ion RM, Fierascu RC, Dumitriu I. Extended spectral analysis (FTIR, EDXRF, ICP-EAS) of cellulose-based artifacts. Studia Universitatis Babes Bolyai, Geologia, Special. 2009;83-86'},{id:"B49",body:'Ion RM, Ion ML, Niculescu VIR, Dumitriu I, Fierascu RC, Florea G, Bercu C, Serban S. Spectral analysis of original and restaurated ancient paper from a Romanian Gospel. Rom. Journal of Physics. 2008;53(5-6):781-791'},{id:"B50",body:'Mosini V, Calvini P, Mattogno G, Righini G. Derivative infrared spectroscopy and electron spectroscopy for chemical analysis of ancient paper documents. Cellulose Chemistry and Technology. 1990;24:263-272'},{id:"B51",body:'Doncea SM, Ion RM, Nuta A, Somoghi R, Ghiurea M. Optical methods of investigation for book papers conservation with nanoparticles. In: SPIE US, editor. Proceeding of SPIE; 2010. p. 78211 F'},{id:"B52",body:'Sierra-Fernández A, Gómez-Villalba LS, Milosevic O, Fort R, Rabanal ME. Synthesis and morpho-structural characterization of nanostructured magnesium hydroxide obtained by a hydrothermal method. Ceramics International. 2014;40:12285-12292. DOI: http://dx.doi.org/10.1016/j.ceramint.2014.04.073'},{id:"B53",body:'Gómez-Villalba LS, López-Arce P, Álvarez de Buergo M, Fort R. Structural stability of a colloidal solution of Ca(OH)2 nanocrystals exposed to high relative humidity conditions. Applied Physics A.2011;104(4):1249-1254. DOI: http://dx.doi.org/10.1007/s00339-011-6457-2'},{id:"B54",body:'Taglieri G, Mondelli C, Daniele V, Pusceddu E, Trapananti A. Synthesis and X-ray diffraction analyses of calcium hydroxide nanoparticles in aqueous suspension. Advances in Materials Physics and Chemistry. 2013;3:108-112. http://dx.doi.org/10.4236/ampc.2013.31A013'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Rodica-Mariana Ion",address:"rodica_ion2000@yahoo.co.uk",affiliation:'
ICECHIM, Research Center for Scientific Investigations and Conservation/Preservation of Industrial, Cultural and Medical Heritage (SCI-HERITAG), Romania
Materials Engineering Department, Research Center “Nanomaterials for Mechanical Microsystems”, Valahia University, Romania
ICECHIM, Research Center for Scientific Investigations and Conservation/Preservation of Industrial, Cultural and Medical Heritage (SCI-HERITAG), Romania
Center of Expertise of Artworks by Advanced Instrumental Methods (CEOAMIA), Ovidius University, Romania
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1. Introduction
Nanoprecipitation is a technique to incorporate active molecules into colloidal drug delivery systems, patented by Fessi et al. [1, 2], which attracts attention for developing pharmaceutical products mainly due to the simplicity of its procedure [3]. The obtained particles enable the optimization of the drug in vivo therapeutic performance exhibiting, for example, controlled release behaviors, target delivery, and better stability in biological fluids, which means major mean residence times, half-lives increased, and more efficient addressing of the actives toward the different body tissues. Consequently, less toxicity and minor secondary effects are expected.
Some of the research works undertaken during the last years have proposed the vectorization in nanoparticles, via nanoprecipitation, of hydrophobic active molecules, mainly exhibiting logP values higher than 3. They include antineoplastics (e.g., doxorubicin [4], paclitaxel [5, 6], docetaxel [7, 8], methotrexate [9], triptolide [6], cucurbitacin [10], and sorafenib [11]), antiretrovirals (e.g., efavirenz [12] and nevirapine [13]), immune suppressants (mycophenolate [14]), anti-inflammatories (clobetasol [15], fluticasone propionate [16], dexamethasone [17, 18], and diclofenac [19]), antimicrobial and antifungal agents (polymyxin B [20], amphotericin B [21], itraconazole [22], and linezolid [23]), antihyperlipidemics (fenofibrate [24, 25]), anesthetics (tetracaine [26] and ketamine [27]), antihypertensives (nimodipine [28] and atenolol [29]), vitamins or their precursors (β-carotene [30] and vitamin E [31]), and antioxidants (quercetin [14, 32]). Likewise, although in a much smaller number, hydrophilic active molecules such alendronate [33], N-acetylcysteine [34], and calcein [35], have been investigated. Moreover, natural extracts such as Brazilian red propolis extract [36] and essential oils [37] have also been incorporated into polymeric nanoparticles.
Practical matters as the possibility to use solvents of low toxic potential, the simple procedure, the low energy consumption required, and the feasibility to obtain particles from diverse compositions are also highlighted among the pros of the nanoprecipitation method when carriers at the submicron and nanometric scales are intended [3, 38]. Most of the nanoparticulated drug delivery systems reported as prepared by nanoprecipitation have been developed by using the physicochemical principles governing this technique, primarily those who underpin the precipitation of materials from the mixture of a solvent/non-solvent for the involved material. They include in their majority, polymer, lipid, and hybrid nanoparticles; therefore, this review will be fundamentally focused on them. Nevertheless, some interesting developments of nanoparticles prepared by nanoprecipitation have been reported as well. For example, Arizaga et al. [39] and Villela et al. [40] entrapped magnetic nanoparticles inside polymeric particles, Fan et al. [41] designed spatially controlled release multistage carriers via the complexation of dendrimers with gelatin, and Allen et al. [35] entrapped hydrophobic and hydrophilic active molecules into polymersomes. Likewise, modifications to facilitate the industrial scaling-up of the preparation process have been investigated by Charcosset et al. [42] and D’Oria et al. [43] who developed procedures based on the use of a membrane contactor. On its part, Valente et al. [44] and Tao et al. [45] propose controllable mixing devices such as microfluidic mixer systems that allow continuous and scalable processes for the synthesis of the particles.
Reviews published to date dealing with the nanoprecipitation technique provide valuable information from different standpoints. For example, regarding the role of the obtained particles as drug delivery systems and their applications in medicine, Martínez et al. [46] highlighted their ability for carrying either natural products or actives obtained via chemical synthesis. On the other hand, with respect to the study of nanoprecipitation as a physicochemical process, Mora-Huertas et al. [47] revised the influence of both the formulation and the work conditions used to prepare nanoparticles. In this case, data available in scientific reports supplemented with a systematic study of the nanoprecipitation method led to an approximation to the particle formation mechanisms and identify the factors influencing the particle properties. Recently, Saad and Prud’homme [48] deepened on the physicochemical principles of the nanoparticle formation when amphiphilic block copolymers are used as stabilizing agents (named flash nanoprecipitation). They focused on the key variables determining the nucleation and growth phenomena related to the particle formation, particularly the supersaturation condition, the mixing step, and the used solvents and stabilizing agents.
Based on the above, the present chapter revises the generalities of the nanoprecipitation technique such as the physicochemical aspects involved, some of the starting materials used to obtain polymer, lipid, and hybrid nanoparticles, and their characteristics. Then, the pharmacokinetic behaviors, safety evaluations, and efficacy tests are analyzed. It is our interest to provide readers with a comprehensive view about the nanoprecipitation as a technique to prepare nanocarriers and its potentialities for developing innovative pharmaceutical products.
2. Physicochemical fundamentals of the nanoprecipitation technique
To prepare nanoparticles via the nanoprecipitation technique, two miscible solvents are used, one of them being a good solvent (usually an organic solvent as ethanol, isopropanol, or acetone) and the other one acting as a non-solvent for the material that will form the particle (i.e., polymer, lipid, etc.), e.g., water. In general, as shown in Figure 1, the nanoprecipitation procedure requires the preparation of an organic phase and a non-solvent phase, frequently named aqueous phase, both guaranteeing the total solubility of all the starting materials. In this sense, the organic phase could contain polymers or solid and liquid lipids, surfactants of low HLB value, and active molecules dissolved in a solvent or mixture of organic solvents. The solubility in the solvent of the active molecule to be entrapped is one of the factors limiting the drug loading of the particles. On its part, the non-solvent phase mainly includes stabilizing agents solubilized in water, which allows the particle formation and the physical stability of the system [2]. Nonetheless, the preparation of particles without stabilizing agents has been reported. In these cases, for example, isoprenoid chains are linked to the active molecule making it easy to form the nanoparticle because of its amphiphilic nature [49].
Figure 1.
General view of the preparation of polymer, lipid, and hybrid particles by nanoprecipitation summarizing the work conditions commonly reported (PNC: polymeric nanocapsules; PNS: polymeric nanospheres; SLN: solid lipid nanoparticles; HNP: hybrid nanoparticles; RT: room temperature).
Nanoparticles are spontaneously formed when the organic phase is dropped or added in a one-shot to the aqueous phase. Indeed, nanoprecipitation is a robust process and operational conditions used to prepare the particles do not seem to have a marked influence on the obtained particle size and polydispersity index. On the contrary, the variables linked to the used formulation appear as determinants of the characteristics of the nanosized system, mainly the nature and concentration of the starting materials [47]. This might be closely related to the proposed mechanisms to form the particles by the nanoprecipitation technique. As a basic premise, only specific polymer/solvent/non-solvent ratios, where the polymer is in low concentrations and the solvent is in low proportion with respect to the nonsolvent, lead to particles at the nano- and submicron levels [50]. Thus, on the one hand, the mechanical approach states that when the phases are mixed, the organic phase is successively broken as drops within the aqueous phase due to the interfacial turbulence and thermal inequalities in the system because of the mutual miscibility between the solvent and the non-solvent and their different interfacial tensions (Gibbs-Marangoni effect) [51]. This fragmentation process will occur until the difference in interfacial tensions is minimized and the organic solvent migrates from the drops having a submicron size, which creates a non-solubility condition for the material causing the precipitation of the particles. On the other hand, a mechanism based on the chemical instability of the system has also been proposed (“ouzo effect”). In this case, when the phases are mixed, supersaturation of the molecules forming the particles is caused as the organic solvent migrates toward the aqueous phase, allowing the formation of “protoparticles” that grow following the classical nucleation-and-growth process [48, 52, 53]. It seems that depending on the formulation to prepare the nanoparticles, one of those mechanisms could predominate during the nanoprecipitation, and consequently, the adequate work conditions should be defined for allowing the spontaneous formation of submicron or nanoscale particle sizes exhibiting the smallest polydispersity indexes. Difficulties associated with the standardization of the procedure of nanoprecipitation result in the polymer aggregation yielding wide and asymmetric particle size distributions. For example, polymer aggregates are evidenced because of a concentrated organic phase, high organic phase ratio, low concentration of stabilizing agent, and poor mixing of the phases [47].
It is worth clarifying that in-depth studies on how particles are formed via the nanoprecipitation technique and the operating variables determining their characteristics have been carried out by using polymeric systems. Regarding lipid nanoparticles, only systematic studies have been reported to aid in understanding the variables that influence the preparation of the carriers; among them, the contributions of Martínez-Acevedo et al. [54] on the influence of the used recipe and Noriega-Pelaez [55] on the study of the particle preparation process are highlighted. Concerning the hybrid particles, research works to date have focused primarily on the impact of the starting materials on the particle characteristics [5, 9, 12, 23, 56].
Once the nanocarriers are formed, the particle dispersions are further processed to purified and concentrate them. To this end, rotary evaporation [14, 18, 22, 23, 24, 31, 55] and centrifugation [5, 6, 12, 13, 15, 16, 23, 25, 27, 28, 29, 36, 56, 57] are the most used methods; however, filtration [4, 6, 16, 18, 24] and dialysis [7, 8, 9, 21, 27, 34] have also been reported. Likewise, lyophilization is the preferred technique to stabilize the nanoparticles, although the storage to low temperatures has been used to preserve the aqueous dispersions [5, 8, 9, 13, 21, 29].
3. Starting materials and general characteristics of particles prepared by nanoprecipitation
As mentioned above, although different types of carriers intended for pharmaceutical applications can be prepared via nanoprecipitation, only polymer, lipid, and hybrid particles were chosen to be analyzed in detail because of the amount of reported research works to date. Polymeric nanoparticles are classified as polymeric nanospheres (PNS) and polymeric nanocapsules (PNC). The first ones correspond to a solid matrix conformed by the used polymers and other components, e.g., active molecules and lipophilic surfactants. On its part, the structure of the nanocapsules is proposed as an oil core surrounded by a polymeric shell. Approximately, 90% of the research works published on the preparation of polymeric nanoparticles via the nanoprecipitation technique are devoted to the obtention of nanospheres.
With respect to lipid nanoparticles, both solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been investigated, although almost 85% of the research works deal with SLN. Lipids nanoparticles are composed of a lipid matrix that is supposed to be surrounded by stabilizing agents. In the case of SLN, the lipid matrix is exclusively formed by solid lipids, while the lipid matrix of NLC is composed of solid and liquid lipids. It seems that the liquid lipid in NLC favors the entrapment efficiency of the active molecules [58].
Regarding hybrid nanoparticles, they are made from both polymers chemically modified with lipids (e.g., 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy polyethylene glycol—DSPE-PEG) or the physical mixture between polymers and lipid components (e.g., PLGA and soy lecithin). Nevertheless, in the latter case, although the qualitative recipe is similar to that for polymeric particles, higher concentrations of solid lipids are used to prepare hybrid particles (i.e., lipid concentrations range between 20 and 50% for hybrid particles and between 1 and 5% for polymeric nanoparticles).
3.1 Starting materials
Figure 2 shows in a comparative way the reported starting materials used to prepare the different types of particles via nanoprecipitation. As can be seen, PLGA, PCL, and PLA are the most used polymers to prepare polymeric nanoparticles and when these polymers are chemically modified with, for example, PEG, stealth polymeric nanoparticles can be obtained [16, 17, 27]. Surfactants of low HLB value, e.g., soy phospholipids, could be added to the organic phase for facilitating the particle formation [19, 31] and, if nanocapsules are intended, castor oil, sesame oil, caprylic capric triglycerides, and caprylic capric triglyceride PEG-4 esters are part of the organic phase. Acetone appears as the preferred organic solvent of the organic phase and the non-solvent is water. Thus, the aqueous phases are solutions of stabilizing agents as poloxamer, polyvinyl alcohol, and polysorbate 80, which prevent the particle aggregation phenomena. Likewise, aqueous phases can only be water [16] or phosphate buffer [27, 59].
Figure 2.
Starting materials reported as used to prepare the organic and aqueous phases for obtaining polymer, lipid, and hybrid nanoparticles by the nanoprecipitation technique. Number of times reported for each starting material considering a total of 18, 11, and 13 research works for polymer, lipid, and hybrid particles, respectively [PLGA: poly(lactic-co-glycolic acid); PCL: polycaprolactone; PLA: poly(lactic acid); PEG: polyethylene glycol; HPMC: hydroxypropyl methylcellulose; DMSO: dimethyl sulfoxide; CAP: cellulose acetate phthalate; EtOH: ethanol; ACN: acetonitrile; MetOH: methanol; DMF: dimethylformamide; DCM: dichloromethane; THF: tetrahydrofuran; MEK: methyl ethyl ketone; H-b-pBG: hyaluronan poly(γ-benzyl-L-glutamate); PBS: phosphate-buffered saline; SDS: sodium dodecyl sulfate; GMS: glycerol monostearate; TPGS: tocopheryl polyethylene glycol succinate; PVA: polyvinyl alcohol; Tf-PEG-OA: transferrin-poly(ethylene glycol)-oleic acid; Tf: transferrin; HSA: human serum albumin; DSPE-PEG: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]].
To prepare SLN, fatty acids and their glyceryl esters are frequently used as lipids (e.g., glyceryl monostearate, tristearate, behenate, and dilaurate); they are dispersed at a molecular level in organic solvents such as acetone and ethanol for obtaining the organic phase. As in the case of polymeric nanoparticles, phospholipids can be used to favor the particle formation and, to make NLC, liquid lipids as caprylic capric triglycerides are also dissolved in the organic phase. With respect to the non-solvent phase, aqueous solutions of stabilizing agents of varied nature are reported. Among them, surfactants as those mentioned for polymeric nanoparticles, proteins such as sodium caseinate and lactoferrin, and osmotic active compounds such as glucose and magnesium sulfate have been investigated.
Hybrid nanoparticles were designed to integrate the favorable characteristics of both polymeric and lipid systems and overcome their drawbacks [34]. These systems are proposed as an inner polymeric core surrounded by a lipid shell [60]. To obtain it, as is the rule in nanoprecipitation, organic and aqueous phases are designed so that solubility of the starting materials is guaranteed. As one of the strategies to prepare hybrid particles is employing polymers chemically modified with lipids (e.g., DSPE-PEG-NH2), they behave as amphiphilic compounds that could form part of any of the phases according to their solubility. On the contrary, if a physical mixture of polymer and lipid is used, they are dissolved in the organic phase. Unlike polymeric and lipid particles, acetonitrile is reported as the most used organic solvent for preparing hybrid nanoparticles. Another interesting matter of the recipe to prepare hybrid nanoparticles is the versatile composition of the aqueous phase. In this sense, for example, lecithin and cholesterol can be dissolved in ethanol and then incorporated in the aqueous phase that could contain surfactants such as polysorbate and poloxamer. Likewise, dispersions of surfactants, proteins, or buffers were tested as the aqueous phase.
3.2 General characteristics of the particles
Regardless of the type of particle, the shape, the particle size, the drug entrapment, and loading, and the zeta potential are among the crucial properties determining their pharmaceutical performance [61].
3.2.1 Shape
Polymeric and hybrid particles prepared by using the nanoprecipitation technique exhibit spherical shape as it is revealed by techniques of microscopy, mainly scanning electron (SEM), transmission electron (TEM), atomic force (AFM), and field emission scanning microscopies (FESEM). To investigate the shape of lipid nanoparticles in most cases, the same techniques were used, and spherical shapes were also reported. However, lipids might be melted during the sample examination destroying their native characteristics; consequently, controversial results could be obtained. For example, platelet shapes for SLN [62, 63] and structures with the liquid lipid located on the surface of the particles in the form of plates for NLC [64, 65] have been reported by using cryo-TEM and freeze-fracture TEM. Nevertheless, Dong et al. [24] report spherical shape from the analysis of SLN by using Cryo-FESEM.
3.2.2 Particle size
In general, the mean sizes, usually measured by dynamic light scattering, vary between less than 100 and 300 nm with PDI values below 0.4 (Figure 3A and B). It seems that polymeric nanocapsules and specially hybrid nanoparticles are the smallest; perhaps, any type of structural arrangement among the lipids and polymers could favor a better consolidation of the particle. With respect to lipid carriers, the platelet shapes as the lipids crystallize inside the particle could explain their high polydispersity [66].
Figure 3.
General behaviors of particle size (A), polydispersity index (B), drug entrapment efficiency (C), and drug loading (D) for polymeric nanospheres (PNS), polymeric nanocapsules (PNC), solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and hybrid nanoparticles (HNP).
3.2.3 Drug entrapment efficiency
Regarding the entrapment efficiency (Figure 3C), clear differences are identified among the carriers. Thus, polymeric nanocapsules entrap almost the totality of the active molecule in contrast with 40% attained by the SNL. As remarked by Westesen et al. [67], Pardeike et al. [68], and Weber et al. [69], when preparing SLN the solidification and the progressive crystallization of the lipid in more stable forms could lead the expulsion of the active substances whether during the particle formation or its consolidation. This results in eventual instabilities of the particle dispersions and, as evidenced in this case, low entrapment efficiency and loading of active molecules. On the other hand, as shown in Figure 3D, the best results of drug loading are reported for hybrid nanoparticles; active molecules could be located both in the polymeric core and the lipid layer of the particles maximizing their loading efficiency.
3.2.4 Physicochemical stability
Stability of the particle dispersions has been investigated by using refrigerated storage [6, 8, 13, 15, 21], room temperature at 25°C [8, 13, 14, 21, 57], and accelerated conditions varying between 35 and 40°C [8, 9, 11, 20, 27]. Particle size, PDI, and zeta potential are usually followed during the storage time, and the physical integrity of the dispersions is observed for up to 6 months. This good stability is expected for these nanosystems considering their colloidal nature and the absolute zeta potential values which are estimated varying between 15 and 40 mV.
3.2.5 Release behavior
Table 1 summarizes the reported work conditions used to carry out the release tests. No matter what type of particles, dialysis is the most used technique to investigate their drug release behaviors, usually at 37°C in PBS media of pH 6.8 or 7.4. Comparisons of drug release data is risked because significant changes in the delivery behaviors are caused by the type of particle and its composition, the nature of the active molecule, and the work conditions associated with the release test, however, worth the risk for gaining a general view.
Thus, even though the mathematical modeling of the drug release data reported for the carriers of interest predicts Higuchi and Korsmeyer-Peppas kinetics, differences in the drug release patterns of polymeric, lipid, and hybrid particles are evidenced (Figure 4). In this way, biphasic release behaviors seem to be characteristic when nanoprecipitated polymeric particles, whether nanospheres or nanocapsules, are investigated. In these cases, the equilibrium is reached after 20 or 30 h of begun the study, and drug concentrations varying from 60 to 80% are released. Paclitaxel-loaded PLGA nanoparticles are the exception; in this case, a slow and constant drug release process occurs delivering hardly 40% of the active encapsulated after 60 h. Perhaps, the low entrapment efficiency of this molecule into the carriers makes the diffusion phenomena related to the active molecule delivery (37–70%) difficult.
On its part, the drug release patterns observed when lipid nanoparticles are tested seem to be those where the active molecule has faster delivery (before the first 20 h) and, at a rate, higher than 80%. Nimodipine reached delivered concentrations near 100% at 10 h, and other molecules such as tetracaine and nevirapine exhibit biphasic behaviors reaching drug deliveries higher than 80% at 25 h. NLC appear to be more efficient than SLN during the release process. The highest amounts of active molecule that could be encapsulated because of the oil component in the particle structure might have influence. Once again, there are exceptions to the general behavior. In this way, slow-release processes as in the case of clobetasol and fenofibrate, lead to less than 40% of active molecule released even at 100 h. It is important to keep in mind that fenofibrate has a high logP value (∼5.2) and that clobetasol propionate was the starting material to prepare the nanoparticles. Thus, a high affinity of the active molecules for the lipid matrix of the particle would difficult its delivery process.
Hybrid nanoparticles, irrespective of whether the particles are obtained from the mixture of polymers and lipids (Figure 4E) or by using chemically modified polymers with lipids (Figure 4F), characterize by a very slow release of the active molecule where, for example, some carriers deliver above 90% of the drug after 50 h of started the test. It should be noted that in this case, the data are reported twice the set time for the other carriers. For some active molecules such as methotrexate, N-acetylcysteine, psoralen, quercetin, and paclitaxel, the prolonged drug release could be related to the uniform distribution presumed for the drug into the matrix and the core-shell structure of the particle, which difficult the diffusion of the drug toward the release medium [9]. Likewise, the hydrolysis and erosion processes of the polymeric core could be hindered by the lipid layer surrounding the polymeric core [34] or, perhaps, the hydrophobic interactions of the active molecule with the polymer might result of relevance for the drug release [5]. These effects offset, for example, the favorable solubility gained because of the precipitation of amorphous active during the preparation of the particles, which is expected to facilitate the drug delivery [9].
4. In vivo performance of carriers prepared by nanoprecipitation
Drug delivery systems such as the polymeric, lipid, and hybrid nanoparticles have been promoted for use in therapeutics as an interesting approach to facilitate uptake of drugs at the desired site of action, particularly when free drugs might give rise to significant off-site toxicities or characterize by poor bioavailability because of their molecular and physicochemical properties. Accordingly, knowing the bioavailability behaviors, including the pharmacokinetic parameters and the biodistribution of the carriers obtained via the nanoprecipitation technique, as well as the stability of the carriers in biological fluids and their cellular uptake, result of paramount importance to investigate their applicability in pharmaceutics.
Considering that submicron sizes for most particles prepared by nanoprecipitation range between 200 and 300 nm, which are larger than pores between endothelial cells, it is expected that, in the absence of specific affinity for receptors, their distribution is limited to the vascular space. Nevertheless, for example, larger endothelial pores such as the fenestrations in the liver and the spleen might lead to the uptake of the particles by these tissues via bulk fluid flow. Once in the bloodstream, particles are coated with a layer of plasma proteins (opsonization or protein corona formation) facilitating their elimination by immune cells. Besides, dynamic interactions between nanoparticles and blood cells, e.g., erythrocytes, platelets, and leukocytes, could occur. Then, the carriers are entrapped in the microvasculature and clearing compartments of the reticuloendothelial system like the liver, the spleen, the bone marrow, and the lung, via phagocytic uptake by cells accessible from the vascular space such us the hepatic Kupffer cells. This allows the elimination of the particles from the organism via the bile ducts into the feces or in the urine [70].
To provide a therapeutic response, nanoparticles must overcome these physiological clearance mechanisms and distributional barriers. The objective is to guarantee a high mean residence time for the carriers in the systemic circulation while their drug release delivery is modulated. Some alternatives in this way include the development of particles exhibiting sizes less than 100 nm or a positive surface charge. Stealth particles by using nonionic polymers or mimic the outer surface of blood cells by locating mixtures of phospholipids, cholesterol, sphingomyelin, and ganglioside molecules on the particle surface have also been proposed, and the modification of the particle surface with specific ligands appears as the best strategy for the target delivery of active substances up to now [61, 70].
Regarding the carriers prepared by nanoprecipitation, among the reported developments of particles that could theoretically allow them a better in vivo performance are: (i) particle sizes lesser than 100 nm for polymeric nanospheres [25, 26, 34], solid lipid nanoparticles [71], and hybrid nanoparticles [7, 34, 56], (ii) positively charged polymeric nanospheres by using chitosan [72] and Eudragit® RL 100 [18] as polymers or positively charged hybrid nanoparticles prepared from lipids as the stearylamine [5], (iii) stealth polymeric nanospheres [17, 27] and stealth hybrid particles [4, 5, 6, 7, 8], and (iv) targeted cancer hybrid particles [7, 59].
4.1 Pharmacokinetic parameters
An approach to the pharmacokinetic aspects of the particles prepared via nanoprecipitation is made from the reported studies where carrier dispersions were administered by the intravenous, oral, and intranasal routes to animal models as Sprague-Dawley rats, Wistar rats, and BALB/c mice (Table 2). First, the slow-release patterns previously discussed appear to be maintained in the in vivo behavior, i.e., nanoparticles extend in some way the drug delivery regardless of the administration route and the carrier properties. Thus, mean residence times (MRT) in the systemic circulation between 1.2 and 20 folds higher than that for the free drug and elimination half-lives between 5 and 10 folds higher than free drug are achieved. Likewise, larger values of area under curve (AUC) are reported which, provided that the amount of drug that is released allows the therapeutic dose required, are attractive for treating chronic diseases where less frequent dosing regimens are convenient.
Summary of the pharmacokinetic parameters reported in research works on nanoparticles prepared by the nanoprecipitation technique.
PNS: polymeric nanospheres; SLN: solid lipid nanoparticles; NLC: nanostructured lipid carriers; HNP: hybrid nanoparticles; Tf: transferrin; P85: Pluronic 85; Tmax: time taken to reach peak plasma concentration; t 1/2: half-life; Cmax: maximum concentration; AUC 0-t: area under the curve of a plasma concentration versus time profile; MRT: mean residence time; P80: polysorbate 80; PEG: poly(ethylene glycol), PLGA: poly (D,L-lactic-coglycolic acid), SH: shellac, nr.: non-reported data.
A general view depending on the administration route (Figure 5, where solid and dashed lines correspond to carriers and free-drug plasma profiles, respectively) shows that polymeric particles orally administered increase the Tmax, Cmax, and AUC0-t values compared with free drugs administered in suspension or, as in the case of lipid nanoparticles, with an intravenously administered solution of the drug. The slow drug release behavior characteristic of lipid particles, where Tmax is abruptly reached after 20 h of administration is interesting. On the other hand, although Tmax, Cmax and, AUC are increased when using hybrid particles, it must be noted that drug could be rapidly or slowly delivered to the serum which might be related to the location of the active molecule into the particle. For example, if the active molecule is located at the lipid shell surrounding the polymeric core, the drug might be easily released; on the contrary, if the active molecule locates at the polymeric core, more extended drug release behaviors could be obtained. Zhu et al. [4] and Godara et al. [5] demonstrate the usefulness of the lipid layer covering the polymeric core in the hybrid particles to prolong the circulation time of the particles. Probably, the lipid shell restricts the plasma protein adsorption reducing the opsonization phenomena. Moreover, the modifications of the particle with cholate enhance the drug absorption by the oral route. Likewise, developments as that of mycophenolate particles containing quercetin, where the antioxidant activity of quercetin inhibits the mycophenolate metabolism through cytochrome P450, are highlighted. This, together with the slow-release pattern of the particles, improves in a significant way the in vivo performance of the hybrid nanoparticles [14].
Figure 5.
General behaviors of plasma concentration reported for polymeric nanoparticles (A and B), lipid nanoparticles (C and D), and hybrid nanoparticles (E and F). Oral administration (A, C, and E); intravenous administration (B, D, and F) (PTX: paclitaxel; FD: free drug; F68: Pluronic 68; HSA: human serum albumin; KET: ketamine; SH: shellac; ITZ: itraconazole; NEV: nevirapine; AmphB: amphotericin B; P80: polysorbate 80; SA: stearylamine; SL: soy lecithin; P: PLGA; MPA: mycophenolate; PVA: polyvinyl alcohol; QUE: quercetin; cHNP: cholate-modified hybrid nanoparticle; DOX: doxorubicin; DTX: docetaxel; P85: Pluronic 85; tf: transferrin).
Concerning the administration of carriers by the intravenous route, pharmacokinetic advantages were also evidenced compared to the free drug administration. As reported by Bian et al. [22] and Han et al. [27], even if a fraction of the polymeric nanoparticles are quickly removed by the reticuloendothelial system during the first 4 h after the administration, the remaining particles into the systemic circulation allow a sustained drug delivery for more than 20 h achieving AUC0-t values from 2 to 10 times higher than free drug. As intended, pegylation of polymeric nanoparticles extends the elimination half-life by ∼100 h and increases in 84% the AUC regarding the free drug [27]. With respect to lipid carriers, Lahkar et al. [13] evidence a significant increase of their AUC0-t which could remain in the blood circulation four times more than the free drug. Moreover, modifications to the particle surface providing some hydrophilicity with polysorbate 80 result in an MRT eight times higher than that of the free drug. Regarding the hybrid nanoparticles, Zhu et al. [4] provide evidence on their extended drug delivery pattern that is improved as modifications on the particle surface are introduced. Thus, plasma circulation of the particles and their corresponding AUC0-t could be prolonged up to six and seven times, respectively, compared with that for the free drug. Jadon and Sharma [8] illustrate results in the same direction where drug delivery from the hybrid particles continues to be detected 72 h after the administration with AUC0-t values around 3.6 times higher than free drug.
4.2 Biodistribution
Figure 6 shows an overview of the organ distribution patterns of the carriers under study as an approximation of their in vivo transport and metabolism processes depending on the route of administration. Perhaps, these behaviors would better correspond to the carried drug since the concentration of the active molecule in the tissues of interest is the measure commonly used to follow the particles in this kind of experiments. Once again, it is the intention to illustrate general behaviors; therefore, the punctual analyses on the particular work conditions used by each research team such as the animal models, the sampling times, and the way as the samples were analyzed are not considered. Thus, caution must be taken to do statements that lead to misinterpretations.
Figure 6.
General behavior of biodistribution for polymer, lipid, and hybrid nanoparticles after administration by oral, intranasal, intrapulmonary, and intravenous routes. Administration by intravenous, intranasal and oral routes (black-filled symbols) and by intrapulmonary route (crossed symbols) (KET: ketamine; NEV: nevirapine; DTX: docetaxel; DZP: diazepam; AmphB: amphotericin B; MPA: mycophenolate; QUE: quercetin).
As can be seen in Figure 6, after 8 h of oral administration of both lipid and hybrid carriers, the liver, the spleen, and the kidney appear as the organs where lipid and hybrid particles are located. This could be attributed to the important role of the liver in the clearance of the particles and the blood filtration function of spleen within the immune system which might also remove the particles of the bloodstream. On its part, drug concentration in the kidney could mean the normal transit of the carrier because of the systemic circulation and the high irrigation of this organ. Nonetheless, the elimination process of intact carriers would also be happening.
On the other hand, as expected, the brain accumulates substantial amounts of lipid nanoparticles administered via intranasal because of the closeness of this organ to the nasal mucosa and its high blood perfusion. This behavior should be harnessed to improve therapies targeted to the brain as those for the treatment of diseases of the central nervous system. Likewise, particles intended for lung cancer therapies, prepared from a hyaluronan-modified polymer, and administered via intrapulmonary route, directly locate on lung up to 24 h [59]. This finding confirms the ability of hyaluronan to be recognized by cancer lung receptors allowing the particle concentration in this tissue and consequently, avoiding the waste of active substance in other organs.
Regarding the intravenous administration, it seems that after 24 h, polymeric nanoparticles mainly locate at the lung, liver, and brain; lipid particles are distributed in blood, liver, kidney, and spleen; and hybrid particles accumulate in the liver. However, it should be noted that regardless of the kind of particle and compared with the oral and intranasal administration, when carriers are administered by intravenous route, drug is found in low levels in all the investigated organs. In addition, after extended periods (e.g., 120 h), particles are more homogeneously distributed among the investigated tissues [27]. This is a natural consequence of the systemic circulation and the irrigation of the different organs. Besides, as previously mentioned, there is a high probability that the concentration of carriers on the liver occurs due to the ability of the hepatic Kupffer cells to phagocyte them. Likewise, the phagocytic activity of the alveolar macrophages could explain why high concentrations of the drug are found in the lung. In addition, to find carriers or active molecules in the stomach might also be possible considering that the pH of this tissue could favor the retention of active molecules exhibiting a basic nature.
It is important to highlight the efficacy of targeted carriers to reach the intended tissues. As it has been evidenced by Jeannot et al. [59], working with polymeric nanoparticles, the functionalization of the polymer with polysaccharide hyaluronan, known for its affinity toward certain cancer cells receptors, allows high concentrations of particles on the lung offering an interesting alternative for the lung cancer treatment. In the same direction, Dehaini et al. [7] demonstrate the ability of docetaxel-loaded hybrid nanoparticles functionalized with folate to reach cancerous tumors.
4.3 Stability in biological fluids
Knowing if nanoparticles aggregate after their in vivo administration is of crucial importance for their application as drug delivery systems. To this end, the colloidal stability of the particulate systems dispersed in biological fluids has been investigated by monitoring variables such as the particle size and the drug encapsulation. Thus, Lazzari et al. [73] demonstrated that polymeric nanospheres prepared by flash nanoprecipitation from PMMA were stable up to 60 h in synthetic saliva, gastric juice, intestinal fluid, and lysosomal fluid while PLA nanoparticles aggregate in gastric juice. Likewise, Dehaini et al. [7] report the aggregation of PLGA nanoparticles in fetal bovine serum (FBS). On the other hand, polymeric nanocapsules coated with brush layers of an oligo ethylene glycol derived methacrylate polymer exhibit major stability in human serum albumin solution, FBS, and human blood plasma, that those non-coated [74]. This evidences the usefulness of designing stealth nanoparticles as a strategy to prevent the particle aggregate formation in blood avoiding their rapid removal from the systemic circulation by the immune system. Regarding SLN, Liu et al. [26] verified their colloidal stability in FBS reporting increases in particle size of approximately 50%, although encapsulation efficiency does not vary. Chaudhari et al. [21] delved into the stability of SLN in simulated gastric fluid confirming that after 2 h, amphotericin B remains encapsulated favoring its stability. With respect to hybrid nanoparticles, contradictory results of aggregation [23] and non-aggregation [7] have been reported when the particle dispersions are mixed with FBS. This can be attributed to the experimental conditions used. In the first case, aggregation is reported after 2 days of storage of the samples at 37°C; in the second one, aggregation was investigated immediately the particle dispersions were diluted. On the other hand, when the stability of hybrid particles was tested in human plasma, interactions of particle and serum proteins were evidenced which increased the carrier size. But what is more interesting is that those interactions seem to be related to the type of stabilizing agent used. As reported by Godara et al. [5], by using PVA or stearylamine as stabilizing agents, particle sizes increased ∼15% that contrast with an increase of ∼50% when particles were stabilized with human serum albumin. Maybe, the protein layer covering the particle surfaces promote their interaction with the serum proteins.
4.4 Cellular uptake
Regarding cellular uptake, Table 3 reports the experimental conditions and general results. Indeed, researches on this regard have been mostly carried out for the hybrid nanoparticles by using human cancer cells taken in their majority from the breast. Nevertheless, some research works have also investigated on prostate and lung cancer cells. Other used cell lines include Caco-2 and MC3T3-E1 osteoblasts. In general terms, the analyses by flow cytometry and confocal laser scanning microscopy reveal that the functionalization of the hybrid particles favors the in vitro cellular uptake when compared to the free drugs and the pattern of cellular uptake correlates with the carrier drug loading.
Nanoparticle
Assay
Experimental conditions
General results
Reference
Cellular model
Tracer molecule concentration
Interaction—cellular model (some work conditions)
Technique of analysis
PNS
CD44 expression levels
Human H322, H358, and A549 NSCLC cell lines
8 μg/mL
30 min at 37 C
Flow cytometry FITC
Dose-dependent binding of NP 30 nm and NP 300 nm, was observed in the three cell lines, with a higher intensity for A549 cells compared with H322 and H358 cells.
Summary of experimental conditions and general results reported in research works on cellular uptake of nanoparticles prepared by the nanoprecipitation technique.
On the other hand, the ability of nanoparticles to penetrate the different physiological barriers and reside in the target tissues has also been demonstrated. For example, SLN could provide efficient in vivo skin permeation [26], polymeric nanoparticles might penetrate mucus also exhibiting mucoadhesive behavior [16], and hybrid nanoparticles would cross the enterocyte walls [32] or reach bone tissue [23].
5. Safety and efficacy of carriers prepared by nanoprecipitation
5.1 Safety
A revision of the starting materials used to prepare particles via nanoprecipitation shows that the polymers and lipids present in the different recipes are recognized as safe considering their biocompatibility. Likewise, most organic solvents are classified as with low toxic potential according to ICH [75]. In the cases where acetonitrile, dichloromethane, tetrahydrofuran, dimethylformamide, and even methanol are used as solvents, the obtained particles should meet the specific requirements of limited concentrations of residual solvent because of their inherent toxicity. Traces of organic solvents would remain in the nanoparticle dispersions after the stage of solvent removal during their preparation. For example, up to 2300 ppm of tetrahydrofuran can be detected in lipid nanoparticles, which exceed the limit of 720 ppm established by the ICH [75]. However, as shown in Table 4, the safety tests including hematological studies on mice [27], hemolysis assays on human blood [8] or with erythrocytes [5], MTT assay on alveolar epithelial cells [34] or osteoblasts [23], cell viability on cancer cells [9, 11], and histological examination of mice [56], evidence concerns on the safety of that particles, and in general, neither of the particles were prepared via nanoprecipitation. Moreover, nanoparticles reduce the toxicity of the active molecules [8, 57].
Nanoparticle
Experimental conditions for toxicity testing
General results
Reference
Cellular/animal model
Assay
Drug concentration or dosage used
Time of interaction—cellular model (h)
Technique of analysis
Polymeric nanoparticles
PNS
Vero cell line (green monkey kidney epithelial cells)
MTT assay
3.12–100 μg/mL
24 h
ELISA microplate reader
Nanoparticles reduce cytotoxicity of the active molecule.
Summary of experimental conditions and general results reported in research works on safety testing of nanoparticles prepared by the nanoprecipitation technique.
One of the promising applications of nanoparticles, including those obtained by nanoprecipitation, is the therapy against cancer. As shown in Table 5, hybrid nanoparticles give good results in this sense. First, the incorporation of the active molecules into the carriers preserve the anticancer activity [9] and nanoparticles offer better performance compared with the free drug [4, 14, 56], in some cases being dose dependent [6, 8, 11]. Besides, significant improvements in the in vivo anticancer performance were achieved by the encapsulation of both an anticancer molecule (mycophenolate) and an antioxidant agent (quercetin) into the same hybrid nanoparticle, as quercetin prevents mycophenolate of its hepatic metabolism via the oxygenase enzymes [14]. Moreover, it was demonstrated that the in vivo tumor treatment in mice prolongs the life of the animals [7].
Nanoparticle
Experimental conditions for efficacy testing
General results
Reference
Assay
Cellular/animal model
Drug concentration
Time of interaction—cellular model
Technique of analysis
Polymeric nanoparticles
PNS (Brazilian red propolis extract)
Antioxidant activity by using DPPH method
—
80 μg/mL
30 min
Spectrophotometry UV
The PNS displayed good antioxidant activity with inhibition values higher than 75%.
Total and differential cell counts on an automated cell counter.
Inhibition of bronchoalveolar lavage fluid (BAL) lavage neutrophils between 50 and 70% in 24 h.
Duration of residence in mouse lung
CF-1 mouse
10 μg of FP per animal
24 h
HPLC/MS
Upon deposition onto respiratory tissue, solution formulations or non-encapsulated drugs are rapidly removed through absorption into systemic circulation compared with nanoparticles.
Half of the mice were still alive at 64 days after tumor challenge. As an indicator of global health, body weights were monitored over the course of the study.
HNP (methotrexate)
Antiproliferation assay
MDB-MB-231 breast cancer and PC3 prostate cancer cells
5, 10, 20, 50, 100, 150, and 200 μg/mL
72 h
ATP-based cell viability kit
MTX encapsulated in the HNP preserve its anticancer activity.
The tumor growth inhibition was (68.9–89.6%). The body weight of the mice in any of HNP treatments groups showed no obvious decrease in comparison with untreated groups.
HNP (paclitaxel)
Cytotoxicity (MTT assay)
A549 human lung adenocarcinoma cells
0.5–10 mg/mL
48 h
Microplate reader
Drugs loaded HNP exhibited marked cytotoxicity on cells in a dose-dependent way and showed higher cytotoxicity compared with their free drug counterparts.
Injured cells (including early apoptosis, late apoptosis, and necrotic cells) with HNP are greater (87%) as compared with free drug (51%).
Antitumor efficiency
BALB/c female mice
10 mg/kg
3 weeks
Tumor width, length and size
The repeated dosing of HNP exhibit less mortality (33%) than with free drug.
HNP (mycophenolate; quercetin)
Annexin V apoptosis assay
MCF-7
10, 20, 40, and 60 μg/mL
6 h
CLSM
Apoptosis indices of MPA-NP and QC-NP are higher compared to respective free drugs. Moreover, the apoptosis index is significantly higher when combination MPA-NP + QC-NP is used.
HNP have higher cellular approachability that accords well with the cellular uptake by Caco-2 cells.
In vivo antileukemic effect
DBA/2 mice
25 mg/kg
21 days
Automatic blood counter
HNP can enhance the oral bioavailability of QC.
HNP (paclitaxel)
Plasma protein binding study
Blood sample from a healthy volunteer
0.7 mg/mL
2 h
Bradford assay
The protein binding of HNP was found between 15.1 and 33.7%. The interaction between the biological environment and HNP can be controlled by surfactant.
Summary of experimental conditions and general results reported in research works on efficacy testing of nanoparticles prepared by the nanoprecipitation technique.
Taken advantage of the slow-release patterns that could be obtained with nanoparticulated systems, the development of carriers exhibiting antimicrobial and anesthetic activities are also of interest in research. Thus, the lowest values of minimum inhibitory concentrations of SLN containing polymyxin B or amphotericin B [20, 21] with respect to the free drugs contribute to support the applicability of nanoparticles prepared by nanoprecipitation in this area. In line with this, polymeric nanoparticles containing Brazilian red propolis extract have also shown antileishmanial activity [36], and linezolid-loaded hybrid nanoparticles demonstrated their ability to be retained in biofilms optimizing their antibacterial performance [23]. Regarding the behavior of nanoparticles in anesthetic and anti-inflammatory tests, tetracaine-loaded SLN exhibited prolonged antinociceptive effect leading to better control of pain [26].
Finally, the possibilities to get target particles prepared by the nanoprecipitation technique have been opened from the research works of Jeannot et al. [59] and Dehaini et al. [7] who investigate hyaluronan and folate as receptors chemically bonded to the polymer obtaining promising results for cancer therapies.
6. Conclusions
Nanoprecipitation is a simple, energy-efficient, and versatile method to entrap active molecules into carriers at the submicron and nanometric levels being the most common developments those oriented to obtain polymer, lipid, and hybrid particles. As the knowledge on the in vivo behavior of nanocarriers progresses and the need to produce them at the industrial scale demands for greater efficiency, the technique and the used starting materials have been optimized to improve the characteristics of the carriers and the control and standardization of continuous processes. In this way, sophisticated devices have been proposed to get sizes lower than 100 nm and the procedure has been refined, either through the chemical modification of polymers or through the careful definition of the work conditions, leading to particles entrapping hydrophobic and hydrophilic molecules, or exhibiting a targeted performance, a positive charge on their surface, or behaviors as stealth carriers. Moreover, the hybrid nanoparticles are promising drug delivery systems where the advantages of both polymeric and lipid particles are harnessed in their design to offer major drug loadings, slow drug-release patterns, and better pharmacokinetic properties. Regardless of the type of carrier, nanoprecipitation seems to be appropriate to obtain safe particles. Even using solvents characterized by inherent toxicity, the satisfactory results achieved by safety tests support their applicability in pharmaceutics. On this basis, it is expected that research on nanoprecipitation will continue looking for innovative solutions to the challenges facing current and future medicine. Some of the findings reported by different research teams and summarized in this chapter provide valuable insights regarding the potentialities of this technique in this respect.
\n',keywords:"nanoprecipitation, nanoparticles, colloidal carriers, drug delivery systems, lipid carriers, hybrid nanoparticles",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72990.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72990.xml",downloadPdfUrl:"/chapter/pdf-download/72990",previewPdfUrl:"/chapter/pdf-preview/72990",totalDownloads:153,totalViews:0,totalCrossrefCites:0,dateSubmitted:"March 17th 2020",dateReviewed:"July 7th 2020",datePrePublished:"August 14th 2020",datePublished:"January 27th 2021",dateFinished:"August 14th 2020",readingETA:"0",abstract:"Nanoprecipitation technique, also named solvent injection, spontaneous emulsification, solvent displacement, solvent diffusion, interfacial deposition, mixing-induced nanoprecipitation, or flash nanoprecipitation, is recognized as a useful and versatile strategy for trapping active molecules on the submicron and nanoscale levels. Thus, these particles could be intended among others, for developing innovative pharmaceutical products bearing advantages as controlled drug release, target therapeutic performance, or improved stability and organoleptic properties. On this basis, this chapter offers readers a comprehensive revision of the state of the art in research on carriers to be used for pharmaceutical applications and developed by the nanoprecipitation method. In this sense, the starting materials, the particle characteristics, and the in vitro and in vivo performances of the most representative of these carriers, i.e., polymer, lipid, and hybrid particles have been analyzed in a comparative way searching for a general view of the obtained behaviors.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72990",risUrl:"/chapter/ris/72990",signatures:"Oscar Iván Martínez-Muñoz, Luis Fernando Ospina-Giraldo and Claudia Elizabeth Mora-Huertas",book:{id:"10116",title:"Nano- and Microencapsulation",subtitle:"Techniques and Applications",fullTitle:"Nano- and Microencapsulation - Techniques and Applications",slug:"nano-and-microencapsulation-techniques-and-applications",publishedDate:"January 27th 2021",bookSignature:"Nedal Abu-Thabit",coverURL:"https://cdn.intechopen.com/books/images_new/10116.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"308436",title:"Associate Prof.",name:"Nedal",middleName:null,surname:"Abu-Thabit",slug:"nedal-abu-thabit",fullName:"Nedal Abu-Thabit"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"320030",title:"Prof.",name:"Claudia Elizabeth",middleName:null,surname:"Mora Huertas",fullName:"Claudia Elizabeth Mora Huertas",slug:"claudia-elizabeth-mora-huertas",email:"cemorah@unal.edu.co",position:null,institution:null},{id:"326041",title:"Prof.",name:"Luis Fernando",middleName:null,surname:"Ospina Giraldo",fullName:"Luis Fernando Ospina Giraldo",slug:"luis-fernando-ospina-giraldo",email:"lfospinag@unal.edu.co",position:null,institution:null},{id:"326042",title:"Mr.",name:"Oscar Iván",middleName:null,surname:"Martínez Muñoz",fullName:"Oscar Iván Martínez Muñoz",slug:"oscar-ivan-martinez-munoz",email:"osmartinezm@unal.edu.co",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Physicochemical fundamentals of the nanoprecipitation technique",level:"1"},{id:"sec_3",title:"3. Starting materials and general characteristics of particles prepared by nanoprecipitation",level:"1"},{id:"sec_3_2",title:"3.1 Starting materials",level:"2"},{id:"sec_4_2",title:"3.2 General characteristics of the particles",level:"2"},{id:"sec_4_3",title:"3.2.1 Shape",level:"3"},{id:"sec_5_3",title:"3.2.2 Particle size",level:"3"},{id:"sec_6_3",title:"3.2.3 Drug entrapment efficiency",level:"3"},{id:"sec_7_3",title:"3.2.4 Physicochemical stability",level:"3"},{id:"sec_8_3",title:"Table 1.",level:"3"},{id:"sec_11",title:"4. In vivo performance of carriers prepared by nanoprecipitation",level:"1"},{id:"sec_11_2",title:"4.1 Pharmacokinetic parameters",level:"2"},{id:"sec_12_2",title:"4.2 Biodistribution",level:"2"},{id:"sec_13_2",title:"4.3 Stability in biological fluids",level:"2"},{id:"sec_14_2",title:"4.4 Cellular uptake",level:"2"},{id:"sec_16",title:"5. Safety and efficacy of carriers prepared by nanoprecipitation",level:"1"},{id:"sec_16_2",title:"5.1 Safety",level:"2"},{id:"sec_17_2",title:"5.2 Efficacy",level:"2"},{id:"sec_19",title:"6. Conclusions",level:"1"}],chapterReferences:[{id:"B1",body:'Fessi H, Puisieux F, Devissaguet JP. Procédé de préparation de systèmes colloïdaux dispersibles d’une substance sous forme de nanocapsules. European Patent 1988;274961 A1, 20 July'},{id:"B2",body:'Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. International Journal of Pharmaceutics. 1989;55:R1-R4. DOI: 10.1016/0378-5173(89)90281-0'},{id:"B3",body:'Schubert S, Delaney JT, Schubert US. Nanoprecipitation and nanoformulation of polymers: From history to powerful possibilities beyond poly (lactic acid). Soft Matter. 2011;7:1581-1588. DOI: 10.1039/c0sm00862a'},{id:"B4",body:'Zhu B, Zhang H, Yu L. Novel transferrin modified and doxorubicin loaded Pluronic 85/lipid-polymeric nanoparticles for the treatment of leukemia: In vitro and in vivo therapeutic effect evaluation. Biomedicine & Pharmacotherapy. 2017;86:547-554. DOI: 10.1016/j.biopha.2016.11.121'},{id:"B5",body:'Godara S, Lather V, Kirthanashri VS, Awasthi R, Pandita D. Lipid-PLGA hybrid nanoparticles of paclitaxel: Preparation, characterization, in vitro and in vivo evaluation. Materials Science and Engineering C. 2020;109:110576. DOI: 10.1016/j.msec.2019.110576'},{id:"B6",body:'Liu J, Cheng H, Han L, Qiang Z, Zhang X, Gao W, et al. Synergistic combination therapy of lung cancer using paclitaxel- and triptolide-coloaded lipid–polymer hybrid nanoparticles. Drug Design, Development and Therapy. 2018;12:3199-3209. DOI: 10.2147/dddt.s172199'},{id:"B7",body:'Dehaini D, Fang RH, Luk BT, Pang Z, Hu CMJ, Kroll AV, et al. Ultra-small lipid–polymer hybrid nanoparticles for tumor-penetrating drug delivery. Nanoscale. 2016;8:14411-14419. DOI: 10.1039/c6nr04091h'},{id:"B8",body:'Jadon RS, Sharma M. Docetaxel-loaded lipid-polymer hybrid nanoparticles for breast cancer therapeutics. Journal of Drug Delivery Science and Technology. 2019;51:475-484. DOI: 10.1016/j.jddst.2019.03.039'},{id:"B9",body:'Tahir N, Madni A, Balasubramanian V, Rehman M, Correia A, Kashif PM, et al. Development and optimization of methotrexate-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery applications. International Journal of Pharmaceutics. 2017;533:156-168. DOI: 10.1016/j.ijpharm.2017.09.061'},{id:"B10",body:'Alshamsan A. Nanoprecipitation is more efficient than emulsion solvent evaporation method to encapsulate cucurbitacin I in PLGA nanoparticles. Saudi Pharmaceutical Journal. 2014;22:219-222. DOI: 10.1016/j.jsps.2013.12.002'},{id:"B11",body:'Tahir N, Madni A, Li W, Correia A, Khan MM, Rahim MA, et al. Microfluidic fabrication and characterization of sorafenib-loaded lipid-polymer hybrid nanoparticles for controlled drug delivery. International Journal of Pharmaceutics. 2020;581:119275. DOI: 10.1016/j.ijpharm.2020.119275'},{id:"B12",body:'Raina H, Kaur S, Jindal AB. Development of efavirenz loaded solid lipid nanoparticles: Risk assessment, quality-by-design (QbD) based optimisation and physicochemical characterisation. Journal of Drug Delivery Science and Technology. 2017;39:180-191. DOI: 10.1016/j.jddst.2017.02.013'},{id:"B13",body:'Lahkar S, Das MK. Surface modified kokum butter lipid nanoparticles for the brain targeted delivery of nevirapine. Journal of Microencapsulation. 2018;35:680-694. DOI: 10.1080/02652048.2019.1573857'},{id:"B14",body:'Patel G, Thakur NS, Kushwah V, Patil MD, Nile SH, Jain S, et al. Mycophenolate co-administration with quercetin via lipid-polymer hybrid nanoparticles for enhanced breast cancer management. Nanomedicine: Nanotechnology, Biology and Medicine. 2020;24:102147. DOI: 10.1016/j.nano.2019.102147'},{id:"B15",body:'Hu FQ, Jiang SP, Du YZ, Yuan H, Ye YQ, Zeng S. Preparation and characteristics of monostearin nanostructured lipid carriers. International Journal of Pharmaceutics. 2006;314:83-89. DOI: 10.1016/j.ijpharma.2006.01.040'},{id:"B16",body:'Popov A, Schopf L, Bourassa J, Chen HB. Enhanced pulmonary delivery of fluticasone propionate in rodents by mucus-penetrating nanoparticles. International Journal of Pharmaceutics. 2016;502:188-197. DOI: 10.1016/j.ijpharm.2016.02.031'},{id:"B17",body:'Albisa A, Piacentini E, Sebastian V, Arruebo M, Santamaria J, Giorno L. Preparation of drug-loaded PLGA-PEG nanoparticles by membrane-assisted nanoprecipitation. Pharmaceutical Research. 2017;34:1296-1308. DOI: 10.1007/s11095-017-2146-y'},{id:"B18",body:'Sahle FF, Gerecke C, Kleuser B, Bodmeier R. Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications. International Journal of Pharmaceutics. 2017;516:21-31. DOI: 10.1016/j.ijpharm.2016.11.029'},{id:"B19",body:'Mora-Huertas CE, Garrigues O, Fessi H, Elaissari A. Nanocapsules prepared via nanoprecipitation and emulsification-diffusion methods: Comparative study. European Journal of Pharmaceutics and Biopharmaceutics. 2012;80:235-239. DOI: 10.1016/j.ejpb.2011.09.013'},{id:"B20",body:'Pattani AS, Mandawgade SD, Patravale VB. Development and comparative anti-microbial evaluation of lipid nanoparticles and nanoemulsion of polymyxin B. Journal of Nanoscience and Nanotechnology. 2006;6:2986-2990. DOI: 10.1166/jnn.2006.459'},{id:"B21",body:'Chaudhari MB, Desai PP, Patel PA, Patravale VB. Solid lipid nanoparticles of amphotericin B (AmbiOnp): In vitro and in vivo assessment towards safe and effective oral treatment module. Drug Delivery and Translational Research. 2016;6:354-364. DOI: 10.1007/s13346-015-0267-6'},{id:"B22",body:'Bian X, Liang S, John J, Hsiao CH, Wei X, Liang D, et al. Development of PLGA-based itraconazole injectable nanospheres for sustained release. International Journal of Nanomedicine. 2013;8:4521-4531. DOI: 10.2147/IJN.S54040'},{id:"B23",body:'Guo P, Buttaro BA, Xue HY, Tran NT, Wong HL. Lipid-polymer hybrid nanoparticles carrying linezolid improve treatment of methicillin-resistant Staphylococcus aureus (MRSA) harbored inside bone cells and biofilms. European Journal of Pharmaceutics and Biopharmaceutics. 2020;151:189-198. DOI: 10.1016/j.ejpb.2020.04.010'},{id:"B24",body:'Dong Y, Ng WK, Shen S, Kim S, Tan RBH. Solid lipid nanoparticles: Continuous and potential large-scale nanoprecipitation production in static mixers. Colloids and Surfaces B: Biointerfaces. 2012;94:68-72. DOI: 10.1016/j.colsurfb.2012.01.018'},{id:"B25",body:'Torres-Flores G, Nazende GT, Emre TA. Preparation of fenofibrate loaded Eudragit L100 nanoparticles by nanoprecipitation method. Materials Today: Proceedings. 2019;13:428-435. DOI: 10.1016/j.matpr.2019.03.176'},{id:"B26",body:'Liu X, Zhao Q. Long-term anesthetic analgesic effects: Comparison of tetracaine loaded polymeric nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers in vitro and in vivo. Biomedicine & Pharmacotherapy. 2019;117:109057. DOI: 10.1016/j.biopha.2019.109057'},{id:"B27",body:'Han FY, Liu Y, Kumar V, Xu W, Yang G, Zhao CX, et al. Sustained-release ketamine-loaded nanoparticles fabricated by sequential nanoprecipitation. International Journal of Pharmaceutics. 2020;581:119291. DOI: 10.1016/j.ijpharm.2020.119291'},{id:"B28",body:'Hu FQ, Zhang Y, Du YZ, Yuan H. Nimodipine loaded lipid nanospheres prepared by solvent diffusion method in a drug saturated aqueous system. International Journal of Pharmaceutics. 2008;348:146-152. DOI: 10.1016/j.ijpharma.2007.07.025'},{id:"B29",body:'Chourasiya V, Bohrey S, Pandey A. Formulation, optimization, characterization and in-vitro drug release kinetics of atenolol loaded PLGA nanoparticles using 33 factorial design for oral delivery. Materials Discovery. 2016;5:1-13. DOI: 10.1016/j.md.2016.12.002'},{id:"B30",body:'Oliveira DRB, Furtado GF, Cunha RL. Solid lipid nanoparticles stabilized by sodium caseinate and lactoferrin. Food Hydrocolloids. 2019;90:321-329. DOI: 10.1016/j.foodhyd.2018.12.025'},{id:"B31",body:'Khayata N, Abdelwahed W, Chehnaa MF, Charcosset C, Fessi H. Preparation of vitamin E loaded nanocapsules by the nanoprecipitation method: From laboratory scale to large scale using a membrane contactor. International Journal of Pharmaceutics. 2012;423:419-427. DOI: 10.1016/j.ijpharma.2011.12.016'},{id:"B32",body:'Lee MK, Lim SJ, Kim CK. Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles. Biomaterials. 2007;28:2137-2146. DOI: 10.1016/j.biomaterials.2007.01.014'},{id:"B33",body:'Miladi K, Sfar S, Fessi H, Elaissari A. Encapsulation of alendronate sodium by nanoprecipitation and double emulsion: From preparation to in vitro studies. Industrial Crops and Products. 2015;72:24-33. DOI: 10.1016/j.indcrop.2015.01.079'},{id:"B34",body:'Ahmaditabar P, Momtazi-Borojeni AA, Rezayan AH, Mahmoodi M, Sahebkar A, Mellat M. Enhanced entrapment and improved in vitro controlled release of N-acetyl cysteine in hybrid PLGA/lecithin nanoparticles prepared using a nanoprecipitation/self-assembly method. Journal of Cellular Biochemistry. 2017;118:4203-4209. DOI: 10.1002/jcb.26070'},{id:"B35",body:'Allen S, Osorio O, Liu YG, Scott E. Facile assembly and loading of theranostic polymersomes via multi-impingement flash nanoprecipitation. Journal of Controlled Release. 2017;262:91-103. DOI: 10.1016/j.jconrel.2017.07.026'},{id:"B36",body:'Do Nascimento TG, Da Silva PF, Azevedo LF, Da Rocha LG, Porto ICCM, Moura TFAL, et al. Polymeric nanoparticles of Brazilian red propolis extract: Preparation, characterization, antioxidant and leishmanicidal activity. Nanoscale Research Letters. 2016;11:301. DOI: 10.1186/s11671-016-1517-3'},{id:"B37",body:'Lammari N, Louaer O, Meniai AH, Elaissari A. Encapsulation of essential oils via nanoprecipitation process: Overview, progress, challenges and prospects. Pharmaceutics. 2020;12:431. DOI: 10.3390/pharmaceutics12050431'},{id:"B38",body:'Mora-Huertas CE, Fessi H, Elaissari A. Polymer-based nanocapsules for drug delivery. International Journal of Pharmaceutics. 2010;385:113-142. DOI: 10.1016/j.ijpharm.2009.10.018'},{id:"B39",body:'Arizaga A, Ibarz G, Piñol R, Urtizberea A. Encapsulation of magnetic nanoparticles in a pH-sensitive poly (4-vinyl pyridine) polymer: A step forward to a multi-responsive system. Journal of Experimental Nanoscience. 2014;9:561-569. DOI: 10.1080/17458080.2012.678393'},{id:"B40",body:'Villela AL, Martynek D, Bautkinová T, Šoó M, Ulbrich P, Raquez J-M, et al. Self-assembly of poly(L-lactide-co-glycolide) and magnetic nanoparticles into nanoclusters for controlled drug delivery. European Polymer Journal. 2020;133:109795. DOI: 10.1016/j.eurpolymj.2020.109795'},{id:"B41",body:'Fan Y, Yuan S, Huo MM, Chaudhuri AS, Zhao M, Wu Z, et al. Spatial controlled multistage nanocarriers through hybridization of dendrimers and gelatin nanoparticles for deep penetration and therapy into tumor tissue. Nanomedicine: Nanotechnology, Biology and Medicine. 2017;13:1399-1410. DOI: 10.1016/j.nano.2017.01.008'},{id:"B42",body:'Charcosset C, El-Harati A, Fessi H. Preparation of solid lipid nanoparticles using a membrane contactor. Journal of Controlled Release. 2005;108:112-120. DOI: 10.1016/j.jconrel.2005.07.023'},{id:"B43",body:'D’oria C, Charcosset C, Barresi AA, Fessi H. Preparation of solid lipid particles by membrane emulsification-influence of process parameters. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2009;338:114-118. DOI: 10.1016/j.colsurfa.2009.01.003'},{id:"B44",body:'Valente I, Celasco E, Marchisio DL, Barresi AA. Nanoprecipitation in confined impinging jets mixers: Production, characterization and scale-up of pegylated nanospheres and nanocapsules for pharmaceutical use. Chemical Engineering Science. 2012;77:217-227. DOI: 10.1016/j.ces.2012.02.050'},{id:"B45",body:'Tao J, Chow SF, Zheng Y. Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles. Acta Pharmaceutica Sinica B. 2019;9:4-18. DOI: 10.1016/j.apsb.2018.11.001'},{id:"B46",body:'Martínez Rivas CJ, Tarhini M, Badri W, Miladi K, Greige-Gerges H, Nazari QA, et al. Nanoprecipitation process: From encapsulation to drug delivery. International Journal of Pharmaceutics. 2017;532:66-81. DOI: 10.1016/j.ijpharm.2017.08.064'},{id:"B47",body:'Mora-Huertas CE, Fessi H, Elaissari A. Influence of process and formulation parameters on the formation of submicron particles by solvent displacement and emulsification-diffusion methods. Advances in Colloid and Interface Science. 2011;163:90-122. DOI: 10.1016/j.cis.2011.02.005'},{id:"B48",body:'Saad WS, Prud’homme RK. Principles of nanoparticle formation by flash nanoprecipitation. Nano Today. 2016;11:212-227. DOI: 10.1016/j.nantod.2016.04.006'},{id:"B49",body:'Couvreur P, Stella B, Reddy LH, Hillaireau H, Dubernet C, Desmaële D, et al. Squalenoyl nanomedicines as potential therapeutics. Nano Letters. 2006;6:2544-2548. DOI: 10.1021/nl061942q'},{id:"B50",body:'Stainmesse S, Orecchioni AM, Nakache E, Puisieux F, Fessi H. Formation and stabilization of a biodegradable polymeric colloidal suspension of nanoparticles. Colloid & Polymer Science. 1995;273:505-511. DOI: 10.1007/BF00656896'},{id:"B51",body:'Quintanar-Guerrero D, Allémann E, Fessi H, Doelker E. Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Development and Industrial Pharmacy. 1998;24(12):1113-1128. DOI: 10.3109/03639049809108571'},{id:"B52",body:'François G, Katz JL. Nanoparticles and nanocapsules created using the ouzo effect: Spontaneous emulsification as an alternative to ultrasonic and high-shear devices. ChemPhysChem. 2005;6:209-216. DOI: 10.1002/cphc.200400527'},{id:"B53",body:'Lepeltier E, Bourgaux C, Couvreur P. Nanoprecipitation and the “ouzo effect”: Application to drug delivery devices. Advanced Drug Delivery Reviews. 2014;71:86-97. DOI: 10.1016/j.addr.2013.12.009'},{id:"B54",body:'Martínez-Acevedo L, Zambrano-Zaragoza M, Vidal-Romero G, Mendoza-Elvira S, Quintanar-Guerrrero D. Evaluation of the lubricating effect of magnesium stearate and glyceryl behenate solid lipid nanoparticles in a direct compression process. International Journal of Pharmaceutics. 2018;545:170-175. DOI: 10.1016/j.ijpharm.2018.05.002'},{id:"B55",body:'Noriega-Pelaez EK, Mendoza-Muñoz N, Ganem-Quintanar A, Quintanar-Guerrero D. Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles. Drug Development and Industrial Pharmacy. 2011;37:160-166. DOI: 10.3109/03639045.2010.50180'},{id:"B56",body:'Du M, Ouyang Y, Meng F, Zhang X, Ma Q, Zhuang Y, et al. Polymer-lipid hybrid nanoparticles: A novel drug delivery system for enhancing the activity of Psoralen against breast cancer. International Journal of Pharmaceutics. 2019;561:274-282. DOI: 10.1016/j.ijpharm.2019.03.006'},{id:"B57",body:'Sharma D, Sharma RK, Sharma N, Gabrani R, Sharma SK, Ali J, et al. Nose-to-brain delivery of PLGA-diazepam nanoparticles. American Association of Pharmaceutical Scientists. 2015;16:1108-1121. DOI: 10.1208/s12249-015-0294-0'},{id:"B58",body:'Jenning V, Thünemann AF, Gohla SH. Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids. International Journal of Pharmaceutics. 2000;199:167-177. DOI: 10.1016/S0378-5173(00)00378-1'},{id:"B59",body:'Jeannot V, Mazzaferro S, Lavaud J, Laetitia V, Henry M, Arboléas M, et al. Targeting CD44 receptor-positive lung tumors using polysaccharide-based nanocarriers: Influence of nanoparticle size and administration rout. Nanomedicine: Nanotechnology, Biology and Medicine. 2015;12:921-932. DOI: 10.1016/j.nano.2015.11.018'},{id:"B60",body:'Tahara K, Karasawa K, Onodera R, Takeuchi H. Feasibility of drug delivery to the eye’s posterior segment by topical instillation of PLGA nanoparticles. Asian Journal of Pharmaceutical Sciences. 2017;12:394-399. DOI: 10.1016/j.ajps.2017.03.002'},{id:"B61",body:'Zhao J, Stenzel MH. Entry of nanoparticles into cells: The importance of nanoparticle properties. Polymer Chemistry. 2018;9:259-273. DOI: 10.1039/C7PY01603D'},{id:"B62",body:'Yin J, Hou Y, Song X, Wang P, Li Y. Cholate-modified polymer-lipid hybrid nanoparticles for oral delivery of quercetin to potentiate the antileukemic effect. International Journal of Nanomedicine. 2019;14:4045-4057. DOI: 10.2147/ijn.s210057'},{id:"B63",body:'Helgason T, Awad TS, Kristbergsson K, McClements DJ, Weiss J. Effect of surfactant surface coverage on formation of solid lipid nanoparticles (SLN). Journal of Colloid and Interface Science. 2009;334:75-81. DOI: 10.1016/j.jcis.2009.03.012'},{id:"B64",body:'Bunjes H, Drechsler M, Koch MHJ, Westesen K. Incorporation of the model drug ubidecarenone into solid lipid nanoparticles. Pharmaceutical Research. 2001;18:287-293. DOI: 10.1023/A:1011042627714'},{id:"B65",body:'Jores K, Mehnert W, Drechsler M, Bunjes H, Johann C, Mäder K. Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. Journal of Controlled Release. 2004;95:217-227. DOI: 10.1016/j.jconrel.2003.11.012'},{id:"B66",body:'Gordillo-Galeano A, Mora-Huertas CE. Solid lipid nanoparticles and nanostructured lipid carriers: A review emphasizing on particle structure and drug release. European Journal of Pharmaceutics and Biopharmaceutics. 2018;133:285-308. DOI: 10.1016/j.ejpb.2018.10.017'},{id:"B67",body:'Westesen K, Bunjes H, Koch MHJ. Physicochemical characterization of lipid nanoparticles and evaluation of their drug loading capacity and sustained release potential. Journal of Controlled Release. 1997;48:223-236. DOI: 10.1016/S0168-3659(97)00046-1'},{id:"B68",body:'Pardeike J, Hommoss A, Müller RH. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products. International Journal of Pharmaceutics. 2009;366:170-184. DOI: 10.1016/j.ijpharm.2008.10.003'},{id:"B69",body:'Weber S, Zimmer A, Pardeike J. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for pulmonary application: A review of the state of the art. European Journal of Pharmaceutics and Biopharmaceutics. 2014;86:7-22. DOI: 10.1016/j.ejpb.2013.08.013'},{id:"B70",body:'Glassman PM, Muzykantov VR. Pharmacokinetic and pharmacodynamic properties of drug delivery systems. The Journal of Pharmacology and Experimental Therapeutics. 2019;370:570-580. DOI: 10.1124/jpet.119.257113'},{id:"B71",body:'Nguyễn CH, Putaux JL, Santoni G, Tfaili S, Fourmentin S, Coty JB, et al. New nanoparticles obtained by co-assembly of amphiphilic cyclodextrins and nonlamellar single-chain lipids: Preparation and characterization. International Journal of Pharmaceutics. 2017;531:444-456. DOI: 10.1016/j.ijpharm.2017.07.007'},{id:"B72",body:'Luque-Alcaraz A, Lizardi-Mendoza J, Goycoolea FM, Higuera-Ciapara I, Argüelles-Monal W. Preparation of chitosan nanoparticles by nanoprecipitation and their ability as a drug nanocarrier. RSC Advances. 2016;6:59250-59256. DOI: 10.1039/c6ra06563e'},{id:"B73",body:'Lazzari S, Moscatelli D, Codari F, Salmona M, Morbidelli M, Diomede L. Colloidal stability of polymeric nanoparticles in biological fluids. Journal of Nanoparticle Research. 2012;14:920-930. DOI: 10.1007/s11051-012-0920-7'},{id:"B74",body:'Rodriguez-Emmenegger C, Jäger A, Jäger E, Stepanek P, Alles AB, Guterres SS, et al. Polymeric nanocapsules ultra stable in complex biological media. Colloids and Surfaces B: Biointerfaces. 2011;83:376-381. DOI: 10.1016/j.colsurfb.2010.12.013'},{id:"B75",body:'International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Impurities: Guideline for residual solvents Q3C (R6). 2016'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Oscar Iván Martínez-Muñoz",address:null,affiliation:'
Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia Sede Bogotá, Bogotá, Colombia
'},{corresp:null,contributorFullName:"Luis Fernando Ospina-Giraldo",address:null,affiliation:'
Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia Sede Bogotá, Bogotá, Colombia
'},{corresp:"yes",contributorFullName:"Claudia Elizabeth Mora-Huertas",address:"cemorah@unal.edu.co",affiliation:'
Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia Sede Bogotá, Bogotá, Colombia
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Meanwhile, due to this increasing demand in industry resulting strict measures in disease control and environmental factors, these products may involve some chemical and natural compounds with hazardous properties at detectable or even very low concentrations. Among these compounds, residues are of concern, including veterinary drugs, environmental pollutants (such as dioxins, pesticides, and phthalates), natural contaminants (mycotoxins, etc), and/or phytosanitary substances accidentally contaminating poultry product during production or marketing stages. In order to keep the consumers safe from the harmful/undesirable effects due to these compounds, such as genotoxic, immunotoxic, carcinogenic, teratogenic, or endocrine disrupting effects, new strategies and concepts for poultry food security have been emerged and developed globally. 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Even though it varies by species and sex, some common effects are reduced feed intake, weight gain, feed efficiency, growth performance, immunity and hatchability along with increased mortality, organ damages (mainly kidney and liver), carcinogenicity, teratogenicity and decreased egg production. Besides their adverse health effects and the decrease in production rate, concerns over their importance in public health is still under debate. Decontamination approaches to reduce mycotoxins in feed are technologically diverse and based on chemical, biological and physical strategies. Chemical remediation strategies involve the conversion of mycotoxins via chemical reactions. Biological strategies involve various substances such as plant ingredients, enzymes and microorganisms. Physical processes include sorting, milling, dehulling, cleaning, heating, irradiation or combinational approaches. New strategies for the prevention and treatment of mycotoxicosis, including beneficial microorganisms/products, along with alternative treatments, including plant extracts/essential oils, are current hot topics in the poultry industry.",signatures:"Ayhan Filazi, Begum Yurdakok-Dikmen, Ozgur Kuzukiran and Ufuk\nTansel Sireli",authors:[{id:"152542",title:"Dr.",name:"Ayhan",surname:"Filazi",fullName:"Ayhan Filazi",slug:"ayhan-filazi",email:"filazi@veterinary.ankara.edu.tr"}],book:{title:"Poultry Science",slug:"poultry-science",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"48251",title:"Prof.",name:"Mehdi",surname:"Razzaghi-Abyaneh",slug:"mehdi-razzaghi-abyaneh",fullName:"Mehdi Razzaghi-Abyaneh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/48251/images/system/48251.jpg",biography:"Prof. Razzaghi-Abyaneh is a research scientist and head of Mycology Department of the Pasteur Institute of Iran where he is working on mycotoxins and mycotoxigenic fungi, antimicrobial nanomaterials, and biologically active compounds of plant, fungal and bacterial origin. He also investigates ecology and genetic diversity of Aspergillus section Flavi and mode of action of antifungal paptides and other small and macromolecules at cellular and molecular level. He has extensive experiences in cell separation and fractionation, protein extraction and purification, enzyme manipulation, molecular genetics, chromatographic (TLC and HPLC) analyses of mycotoxins, purification of plant antifungal metabolites and electron microscopy of filamentous fungi. 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Open Access publishing helps remove barriers and allows everyone to access valuable information, but article and book processing charges also exclude talented authors and editors who can’t afford to pay. The goal of our Women in Science program is to charge zero APCs, so none of our authors or editors have to pay for publication.
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