Experimental studies using nanosystems for CL treatment.
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Author of more than 100 publications, awarded three Doctorate degrees and the National End of Degree Award, granted by the Ministry of Education to the best academic records of Bachelor's degrees in Spain. Dr. Ortega-Sánchez has been Vice-Rector for Social Responsibility, Culture, and Sports at the University of Burgos since 2021.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"302925",title:"Ph.D.",name:"Delfín",middleName:null,surname:"Ortega-Sánchez",slug:"delfin-ortega-sanchez",fullName:"Delfín Ortega-Sánchez",profilePictureURL:"https://mts.intechopen.com/storage/users/302925/images/system/302925.jpg",biography:"I hold a PhD in Didactics of Social Sciences from the Autonomous University of Barcelona, a PhD in Educational Sciences from the University of Burgos, and a PhD in History from the University of Extremadura. My research interests focus on the construction of identities in the History and Geography teaching, gender mainstreaming in initial education and training for teachers, the didactic treatment of relevant social problems and controversial issues in the teaching of the social and human sciences, and the application of educational technology in the specific field of social sciences. I am currently a Social Sciences teacher and researcher at University of Burgos (Spain).",institutionString:"University of Burgos",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Burgos",institutionURL:null,country:{name:"Spain"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"23",title:"Social Sciences",slug:"social-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429339",firstName:"Jelena",lastName:"Vrdoljak",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429339/images/20012_n.jpg",email:"jelena.v@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Although not fatal as VL, CL is the most common form of leishmaniasis and a serious public health problem. According to the World Health Organization (WHO) estimates, CL is endemic in 87 countries, with almost 200,000 new cases reported in 2015 [1]. From 2005 to 2013, CL-associated morbidity increased by 175% of disability-adjusted life years (DALYs) [2]. The impact of CL may be much greater considering the high under-reported cases and estimation that one fourth of the world population (1.7 billion people) live in area at risk of infection [3]. In addition, inadequate disease control may promote the progression of CL to more morbid and undefined subforms, such as diffuse CL and mucosal leishmaniasis (ML).
In the great majority (>90%) of cases worldwide, CL is of the uncomplicated type, with 1–4 localized skin ulcers, not larger than 3–4 cm diameter, with a raised border and central depression [4]. Even with localized manifestation, current treatment is normally based in the daily administration of intramuscular or intravenous injections with antimonials, pentamidine, or amphotericin B for 20–30 days. Besides limited to few drugs, and occurrence of drug resistance, available CL treatment produces unacceptable systemic toxicity [5].
Ideally, CL chemotherapy as proposed by Drugs for Neglected Diseases initiative (DNDi) should be efficacious against all species, compatible in combination therapy, safe in pregnant and breastfeeding women, and administered by oral or topical route [6]. However, oral and topical therapies have shown limited efficacy.
The major challenge in CL treatment is the preferred intracellular parasite location in macrophage phagolysosomes. That hinders drug access, making treatment with conventional formulations especially difficult [7].
Thus, the search for new drugs with different mechanisms of action and innovative forms of drug delivery systems appropriate for the effective treatment of CL is urgently needed. In that context, nanotechnology has emerged as an interesting strategy to increase drug potency and reduce toxicity.
Nanotechnology consists of the development of systems, structures, or devices in the nanometric scale, presenting at least one novel/superior characteristic or property over the original [8]. The use of nanostructured particles for drug delivery is a promising strategy due to their versatility. Besides, they may: (i) protect the drug against physical, chemical, and/or enzymatic degradation, (ii) enhance the pharmacokinetic properties, and (iii) improve bioavailability. They may also be functionalized for drug release at a specific site and thereby reduce systemic toxicity [7]. Furthermore, leishmaniasis is a particularly interesting disease to be treated with drug-loaded nanoparticles since the parasites almost exclusively infect the highly phagocytic macrophages. In this way, the infected cells of the skin (CL) or deep organs (VL) take up the nanoparticulated drug, which will reach the parasitophorous vacuole and act directly on the parasite (Figure 1). This allows the drug to reach an effective intracellular concentration, allowing dose and toxicity reduction. Particle uptake may be further increased with surface functionalization with receptor-binding ligands like mannose or mannan [9].
Nanoparticle drug delivery to intracellular parasites. A drug-loaded lipid or polymeric nanoparticle (Np, yellow) reaches the
Interest in designing nanomedicines for CL has grown over the years, as seen by the steady increase in scientific publications. Several nanosystems, such as liposomes [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20], solid lipid nanoparticles [21, 22], lipid complexes [23, 24], lipid-core nanocapsules [25], polymeric particles [26, 27, 28, 29, 30, 31], inorganic nanoparticle [32, 33, 34, 35], cyclodextrins complexes [36, 37], and drug nanoparticles [38] have been tested
Routes | Drug | Nanosystem | Parasite | Efficacy | Ref |
---|---|---|---|---|---|
Amphotericin B | Chitosan and chondroitin sulfate nanoparticles | Yes | [26] | ||
Amphotericin B | Poloxamer 407-micelles | Yes | [27] | ||
Amphotericin B | PLGA-DMSA nanoparticles | Yes | [28] | ||
Amphotericin B | Liposome | No | [10] | ||
Amphotericin B | Liposome (Ambisome®) | Yes | [11] | ||
Amphotericin B | DSHemsPC-liposome | Yes | [12] | ||
Amphotericin B | Nanodisks | Yes | [23] | ||
Amphotericin B | PADRE-derivatized-dendrimer complexed with liposome | Yes | [13] | ||
Chalcone DMC | PLA Nanoparticles | Yes | [29] | ||
Nanoselenium | Inorganic nanoparticle | Yes | [33] | ||
Paromomycin | Solid lipid nanoparticle | Yes | [21] | ||
Paromomycin | Solid lipid nanoparticle | Yes | [22] | ||
Pentamidine | Methacrylate nanoparticles | Yes | [30] | ||
Pentavalent antimonial | Nanohybrid hydrosols | Yes | [38] | ||
Sodium stibogluconate | Liposome | Yes | [14] | ||
Quercetin | Lipid-core nanocapsules | Yes | [25] | ||
Meglumine antimoniate | Beta-cyclodextrin | Yes | [36] | ||
Meglumine antimoniate | Polarity-sensitive nanocarrier | Yes | [24] | ||
Amphotericin B | Liposome | No | [15] | ||
Amphotericin B | Gamma-cyclodextrin | Yes | [37] | ||
Chalcone CH8 | Liposome | Yes | [16] | ||
Paromomycin | Liposome | Yes | [17] | ||
Paromomycin | Liposome | Yes | [18] | ||
Meglumine antimoniate | Liposome | Yes | [19] | ||
Nanosilver | Inorganic nanoparticles | No | [32] [34] | ||
Nanosilver | Inorganic nanoparticles | No | |||
Amphotericin B | Liposome (Ambisome®) | No | [11] | ||
Chalcone CH8 | PLGA microparticles | Yes | [31] | ||
Nanosilver | Inorganic nanoparticles | Yes | [35] | ||
Meglumine antimoniate | Liposome | No | [20] | ||
Miltefosine | Liposome | Yes | [20] | ||
Paromomycin | Liposome | No | [20] | ||
Paromomycin | Solid lipid nanoparticle | Yes | [22] | ||
Sodium stibogluconate | Liposome | Yes | [14] |
Experimental studies using nanosystems for CL treatment.
Note: Chalcone DMC – 2’,6’-dihydroxy-4’-methoxychalcone; Chalcone CH8 – 3-nitro-2’-hydro-4’,6’-dimethoxychalcone; DMSA – dimercaptosuccinic acid; DSHemsPC – 1,2-distigmasterylhemi-succinoyl-sn-glycero-3-phosphocholine; PADRE – pan DR-binding epitope; PLA – poly(D,L-lactide); PLGA – poly(lactic-co-glycolic acid); UVB – ultraviolet B radiation.
Advances and challenges of nanotechnology use in leishmaniasis treatment, especially for VL, have been extensively reviewed recently [7, 39, 40]. Here, we attempted to identify some of the opportunities and challenges of using nanotechnology to improve CL treatment. For that, mainly
For more than 70 years, injectable pentavalent antimonials such as meglumine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®) have been the first-choice drugs in most countries. The paucity of new effective drugs in the market is due to lack of investment/economic interest for the discovery of therapeutic alternatives. The therapeutic regimen consists of intramuscular or intravenous daily injections for 20–30 days. The long period of treatment leads to the accumulation of antimony (Sb) in the tissues, producing myalgia, pancreatitis, pancytopenia, hepatic and cardiotoxicity [41]. Other limiting factors are drug resistance and increased therapeutic failure [42]. In India, its use in VL has been contraindicated due to the appearance of resistant
In Sb-refractory cases, injectable pentamidine, amphotericin B or paromomycin are used. Pentamidine acts on the DNA synthesis of the parasite and has similar efficacy to antimonials, but also produces side effects such as hypoglycemia, diabetes, tachycardia, hypotension, nephrotoxicity and pain at the site of administration [44]. Like antimonials, cases of pentamidine resistance have been increasing, compromising their use in many endemic regions [45].
Amphotericin B is a polyene antibiotic mostly used in VL and in the disfiguring CL form, mucosal leishmaniasis, administered intravenously for 20 days, usually under hospital admission. This is the most efficacious antileishmanial drug, but it produces serious side effects due to its low solubility (nephrotoxicity), and secondary affinity not only for the parasite ergosterol but also for the host cholesterol, causing hypokalemia and cardiotoxicity [5]. Formulations of amphotericin B in lipids have led to a marked improvement in their plasma solubility and bioavailability. Three lipid formulations are commercially available: unilamellar liposomes (Ambisome®), lipid complex (Abelcet®) and colloidal cholesterol suspension (Amphocil®). Among these, Ambisome® has the highest plasma half-life, lowest toxicity, and highest efficacy against VL and CL models [46, 47]. In some countries, Ambisome® is already recommended as the first-choice drug for the treatment of VL and ML difficult cases. However, its high cost, the undefined optimum dosing regimen, toxicity, and the greater uptake of liposomes by the liver make its widespread use in the treatment of CL unfeasible [48].
The interest in the administration of nanosystems by parenteral routes has been increased, mainly for VL, since they increase the drug bioavailability and depending on the charge, size and composition accumulate preferentially in organs such as liver. In addition, nanosystems can be conjugated to biological compounds, such as peptides, antibodies and mannose, favoring their targeting to macrophages [9]. Thus, even with the dose reduction, the encapsulated drugs present greater efficacy and reduction of toxic effects. To date, most experimental studies are conducted parenterally that include chitosan and chondroitin sulfate nanoparticles, Poloxamer 407-micelles, PLGA-DMSA nanoparticles, PADRE-derivatized dendrimer complexed with liposomes, PLA nanoparticles, solid lipid nanoparticles, methacrylate nanoparticles, and liposomes (Table 1). Since amphotericin B is currently the most potent antileishmanial agent, most studies have used it in order to improve its specificity and reduce its adverse effects [10, 11, 12, 23, 26, 27, 28]. Despite the promising effects of nanomedicines obtained so far, Ambisome® remains the only nanomedicine approved for leishmaniasis parenteral treatment.
Another interesting strategy in the treatment of CL is the use of inorganic nanoparticles, such as nanoselenium, nanosilver and nanotitanium dioxide. Despite the promising efficacy of injected nanosilver [35] and nanoselenium [33] in CL models, the use of nanosilver by topical route was ineffective [32, 34], probably due to the lack of nanoparticle permeation through the infected skin, since those particles were directly active against culture parasites. Nanosilver may act directly on the
The experimental parenteral routes are normally intravenous or intraperitoneal, the latter not applicable in clinical usage. An important issue to be considered when nanoparticles are intravenously injected is the possibility of thrombosis induction [50]. However, small and submicrometric they may be, larger aggregates can form and clog small veins [51]. Therefore, for safety reasons, intralesional, topical and oral routes should be preferable for CL treatment.
The oral route is recommended for both CL and VL due to the ease of administration, high patient compliance, and versatility to increase drug bioavailability. However, systemic adverse effects cannot be precluded.
Miltefosine, a hexadecylphosphocholine previously used to treat cancer, is the only oral drug approved in VL treatment, with good cure rates in India, Nepal, and Bangladesh. However, its teratogenic potential, poor efficacy in patients coinfected with VL and human immunodeficiency virus and recently high rates of clinical failures have increasingly restricted its use in combination therapy [52]. Data on the efficacy of miltefosine in CL treatment are inconclusive, with a large variation depending on the parasite species and geographical area [53].
Another oral drug, allopurinol, an inhibitor of xanthine oxidase, has been explored since 1982 when its activity was demonstrated
Local therapies are the ideal way to treat uncomplicated CL, as they avoid unnecessary systemic side effects. This topic was subdivided in topical and intralesional treatments due to their different delivery approaches.
Topical CL treatment may be provided with chemical drugs or physical methods, such as thermotherapy and cryotherapy. Thermotherapy is the application of high temperature (>50°C) at the center and border of each lesion, based on the inability of
Topical drug treatment of CL normally involves administration of drugs in the form of ointments, creams or gels. These should be ideal for uncomplicated CL due to reduced hospital costs, since it can be auto-applied [44]. The most studied topical formulations are paromomycin creams and gels. The low skin permeation of paromomycin requires association with strong permeants, such as methylbenzethonium chloride, urea and surfactant-associated gentamicin (WR-279396), which may produce local burn and skin irritation [68]. To circumvent that, some formulations have used the milder urea permeant; however, clinical efficacy remains variable depending on the parasite species and geographical area [4]. The results with the WR-279396 formulation are also conflicting, showing high efficacy in patients infected with
Recently, DNDi supported a Phase Ib and II clinical study in Colombia evaluating the safety, pharmacokinetics, and efficacy of Anfoleish, a cream formulation containing 3% amphotericin B [71]. However, limited efficacy was found after topical application in patients infected with
For an optimal topical formulation, the drug should be highly effective and have a high permeation through the skin, reaching the parasite in the deep dermal layer in effective concentrations. For the drug to successfully permeate the stratum corneum, it must possess adequate lipophilicity and a molecular size below 500 Da. The failure or partial success of the topical formulations of paromomycin (615 Da) and amphotericin B (924 Da) is directly related to the low permeability of these drugs through the skin, probably due to their high molecular size [72]. In addition, the typical morphology of CL ulcer with necrotic center and high borders influences the permeation of drugs. Although local inflammatory reaction may facilitate the permeation of more hydrophilic drugs [68], infected macrophages are located in the border of the lesions where epidermal thickening occurs, with hyperplasia and increased number of cell layers, which may hamper drug permeation.
Topical liposomes have emerged as an advantageous way to overlay this problem by increasing drug skin permeation. In fact, some studies have shown the efficacy of liposomes loaded with paromomycin [17, 18] or meglumine antimoniate [19] in
In the search for new active drugs for leishmaniasis, our group has been studying the chalcone CH8 (3-nitro-2’-hydro-4’,6’-dimethoxychalcone), a nitrosylated derivative of the plant-derived chalcone (DMC – 2’,6’-dihydroxy-4’-methoxychalcone), which demonstrated a high selectivity index (SI = 143) and antileishmanial activity
Notwithstanding, the high phospholipid cost and liposomal instability hinder their use for CL. Thus, other nanosystems such as gamma-cyclodextrin have been studied for amphotericin B skin delivery to improve drug solubility and topical efficacy in
Intralesional drug administration is an alternative local treatment for CL. This is especially appropriate for patients with uncomplicated localized CL—up to four lesions, each no more than 3 cm in diameter, as well as parenteral medication restrictions due to systemic toxicity. Besides the lesser toxicity, local subcutaneous injections can accelerate clinical cure and reduce hospital costs as less injections are needed [4]. Pentavalent antimonials are the most used drugs, showing 68–100% efficacy in different clinical studies, depending on the size of the lesions [78, 79, 80, 81]. Repeated injections are required due to the high solubility that favors rapid absorption into the circulation. Treatment generally consists of 1–5 injections around each lesion per day, twice a week. In addition to the pain inflicted, adverse effects like local hyperpigmentation and anaphylactic shock have been reported [82].
Amphotericin B has also been tested by intralesional route in Iran in patients refractory to antimony therapy, leading to complete lesion remission in 61% of the cases [83]. Due to the necrotizing effect of deoxycholate surfactant in amphotericin B formulation, the amount injected has to be as low as possible, reducing effectiveness. Thus, despite its high potential in CL, intralesional treatments need improvement, particularly as regards dose number reduction.
Intralesional drug-loaded nanoparticles have appeared as interesting drug delivery systems in CL due to direct drug delivery to the infected macrophages. However, for the formulation to be effective, drug chemistry, nanosystem choice, and treatment schedule must be finely adjusted. Lipid systems such as SLN loaded with paromomycin have been tested intralesionally in
In this context, polymeric particles have emerged as an interesting strategy for CL intralesional and single-dose treatment. The advantage of this system is that particles smaller than 6 μM can be easily phagocytosed by infected macrophages releasing the drug directly into the target, whereas the larger microparticles form a depot slowly releasing the drug into the site, allowing at only one dose the drug to remain in the site of infection for the time needed for healing. The size of the microparticles and their polymer composition ensures retention of the drug in the lesion and determines its release time. In this way, adverse systemic effects are avoided and the effectiveness of the drug is increased. Recently, the safety and efficacy of PLGA microparticles containing chalcone CH8 in the intralesional treatment was demonstrated in
Since nanomedicines can be more efficiently taken up by the infected macrophages than free drugs, and also be designed to cross skin and epithelial barriers, they have emerged as promising strategies to allow novel topical and oral treatments for CL. Noteworthy is the possibility to treat the disease with a single local injection with biodegradable polymeric particles. Despite the promising results obtained with the different nanomedicines in pre-clinical studies, so far none has so far progressed to clinical trials in CL. Therefore, further efforts must be made in order to have them in the near future in the antileishmanial therapy arsenal.
A.J. Sousa-Batista is a recipient of Rio de Janeiro State Research Foundation—FAPERJ post-doc grant # E-26/202.401/2017.
The authors have no conflict of interest to declare.
In recent decades, our societies have been confronted with climatic disturbances and resource use, leading to the degradation of ecosystems. In order to combat these threatening changes, the international community is committed to finding new ways of producing and creating value, including light-weighting structures and the valorization of lignocellulosic biomass as possible solutions towards sustainable innovation [1, 2, 3]. Indeed, light-weighting implies a reduction in production energy, raw materials produced and materials to be managed at the end of life [4, 5]. The reduction in mass also leads to a reduction in the energy consumption of means of transport and their emissions of pollutants. For these reasons, sandwich structures are increasingly used instead of monolithic structures in various applications, thanks to their lightness, their mechanical performance in bending and their thermal, vibratory, and acoustic features.
Because of their good features, they may be found in vital industries such as aeronautics, automotive, sports, marine, and construction. These properties include high mechanical strength and stiffness, high-impact resistance, low weight, corrosion resistance, and low maintenance costs [6]. Traditionally, composite materials are reinforced with synthetic fibers such as glass, carbon, aramid, or ceramic fibers. These fibers are used because of their strength, stiffness, low moisture absorption, and good compatibility with polymer resins. Glass fibers are the most commonly used because of their low cost, ease of production, and specific mechanical characteristics.
The epoxy matrix combined with rigid fiber allows for the creation of building materials with high stiffness and strength. Given the variety of technical and material options, developing a composite material necessitates taking into account the chemical and physical interactions between all components [7]. As a result, the effects of production processes, fiber reinforcement type, and reactive or nonreactive modifiers on the characteristics of epoxy composites remain intriguing study issues. Many different types of synthetic and natural fibers are used to strengthen the epoxy matrix, including glass, carbon, basalt, aramid, ramie, hemp, jute, and flax [8].
In this chapter, a detailed description of epoxy polymer was represented. Moreover, various fiber types such as glass, carbon, and plant materials. In addition, some fabrication procedures of epoxy reinforced fiber composite are reported. Furthermore, a representation of some applications was described as well as the coming challenges.
Epoxy resin is a thermosetting polymer. It comprises two parts: an epoxy base catalyst and an amine-containing hardener (-NH2 or -NH). During cross-linking, each hydrogen atom in the amine group opens the epoxy ring and produces a polymer chain (Figure 1) [9]. The glass transition temperature denoted T𝑔, increases with the rate of crosslinking. Thanks to its 3D polymeric structure and high phase change temperature, epoxy phase change temperature, epoxy achieves good mechanical and thermal properties [10].
Main chemical reactions taking place during the curing of an epoxy resin.
Table 1 shows the advantages and disadvantages of epoxy thermoset resin. Compared to thermoplastic resins, epoxy resins are more brittle on impact due to their susceptibility to cracking. According to Vieille et al. [12], the impact response of thermoset matrix composites has some weak points:
For the same impact energy, the delamination area due to impact is higher compared to thermoplastic matrix composites;
For impact energy of 25 J, the epoxy reinforced structure is perforated while the maximum displacement of the thermoplastic composite structure is around 11.4 mm;
For the same level of impact energy, the ratio of dissipated energy to impact energy of the epoxy matrix composite is higher than the ratio obtained for the thermoplastic matrix composite. The risk of perforation of the structure increases with the increase of this ratio.
Thermosetting epoxy resin | |
---|---|
Benefits | Disadvantages |
Mechanical properties superior to those of polymers of the same family (tensile, compression, aging, etc.); | Preservation at low temperature (for prepregs or single-component resin); |
Good temperature resistance from 150–190°C approximately; | Long curing time; |
Excellent chemical resistance; | High cost (about 5 times more than polyester resin); |
Low molding shrinkage (0.5 to 1%); | Need to take precautions during implementation; |
Good wettability of the reinforcements; | Sensitivity to cracking. |
Bonne adhérence aux matériaux métalliques. | — |
Advantages and disadvantages of epoxy resin [11].
Moreover, a high brittleness of this family of resins is also the cause of the pseudoplastic behavior of the composite. Upon impact, the opening of intralaminar and interlaminar cracks is triggered. At the same time, epoxy debris forms and blocks the closure of the cracks after impact, which is impact, which is unfavorable to the impact resistance of the composite [13].
Composite materials are categorized based on their content, which includes the base material (matrix) and the filler material. A matrix or binder material is the basic material that binds or retains the filler material in structures, whereas filler material is present in the form of sheets, pieces, particles, fibers, or whiskers of natural or synthetic material. Composite based fibers are categorized into three major groups based on their structure, as shown in Figure 2.
Composites structure types.
Fiber or particulate inclusions in epoxy matrix with different types and shapes are studied by many researchers to characterize their mechanical, electrical, thermal and so on properties [14, 15, 16, 17]. Glass fibers are the most often used synthetic fibers because of their high strength and durability, thermal stability, impact resistance, chemical, friction, and wear qualities. However, machining glass fiber-reinforced polymers (GFRPs) using traditional machining techniques is generally slow, difficult, and results in lower tool life [18]. They are easily made from raw material, which is readily available in an almost limitless supply. There are numerous types of GFs that are often utilized in GFRP composites, depending on the raw materials used and their quantities in fabrication (see Figure 3). GFs also have the disadvantage of being disposed of at the end of their useful life [19]. Glass fiber reinforced polymer composites were created using various production technologies and are widely employed in a variety of applications [20]. Because of their superior mechanical qualities, glass fiber reinforced composites have received more attention in recent years. Glass fibers have excellent features such as high strength, flexibility, stiffness, durability, and so on. The characteristics of GFRP composites improved when the amount of glass fiber was increased. The mechanical and thermal properties of different polymer composites reinforced with glass fiber when exposed to mechanical stress are been listed in the following Table 2.
Glass classification.
Fiber glass type | Manufacturing procedure | Composite structure type | Reference |
---|---|---|---|
E-Glass fiber | Hand lay-up technique | — | [21] |
E-Glass fiber | Hand lay-up | Randomly oriented | [22] |
Glass Fabrics | hand layup vacuum bagging | — | [23] |
C-Glass fiber | Hand lay-up | Randomly oriented | [24] |
E-Glass fiber | Open layup molding | — | [25] |
D-Glass fiber | Hand lay-up techniques | Randomly oriented | [26] |
Example of composites-based epoxy reinforced glass fibers.
Carbon fibers were first used in 1880 by T. Edison as a filament in lamps. From 1960 onwards, research was directed towards the development of high modulus and high strength carbon fibers. The carbon fibers are more required in applications that need more stiffness. Carbon fiber-reinforced polymer (CFRP) composites have extensive uses in aircraft, automotive, sports, and a variety of other sectors. In the literature, many other fillers type such as particulate and fiber fillers [27, 28]. In general, carbon fibers can be categorized by their mechanical properties, manufacturing methods, application field, precursor, fiber materials, final heat treatment temperature, and their function.
Nowadays, industrial businesses are concentrating on providing environmentally friendly products, and the globe is moving towards sustainable development. Because of their biodegradability, natural fibers are employed in the production of such eco-friendly products. The key causes influencing the rising use of natural fiber-reinforced composites are increased awareness of concerns such as pollution, waste of raw materials and energy, and depletion of petroleum reserves (FRC). Due to their lightness, mechanical performance, ability to integrate functions, physical–chemical resistance, and ease of processing, composite materials have made considerable progress in terms of volume and have dominated practically all sectors. Such as wood fiber which are transformed using the steam explosion process and are treated at various steam pressures. Because of the increased explosion pressure, the fiber’s affinity for water, mechanical characteristics, and dissolving ability in caustic solution diminish after the steam explosion [29].
The preferred procedure is determined mostly by the resin used, the length of the fibers, the required qualities of the composite material, and the production run and rate (Figure 4) [30].
Contact molding: It is a procedure for short series. On a waxed mold, layers of catalyzed resin and layers of cloth are alternatively deposited. After applying the resin to the reinforcement with a brush, it is debulked with a roller. This process is continued until the appropriate number of layers has been attained. This method is easy and economical, and it allows for the fabrication of pieces of any form and size with a nice surface look on the mold side. The component produced by this approach is heavily reliant on the molder’s competence.
Vacuum molding: This is a method for producing medium-sized series. Following the placement of the reinforcements and resin on a waxed hard mold, a waterproof membrane is applied to the whole structure. A vacuum established between the mold and the membrane by a vacuum pump allows the resin to be distributed and debulked. The suction is kept up until the resin is completely dry.
Low-pressure liquid resin injection molding: This method is also known as RTM (Resin Transfer Molding). It entails inserting the reinforcements into a hard, waxed, two-sided mold. The catalyzed resin is then pumped into the mold at pressures ranging from 0.1 to 0.4 MPa.
Filament winding: This automated method is intended for the high-pressure molding of high-performance innovative parts like tubes and fluid storage tanks. The method entails dipping rovings in a bath of catalyzed resin before wrapping them around a mandrel. There are three forms of winding based on the speed of movement of the roving in proportion to the angle and speed of rotation of the mandrel: circumferential winding, polar winding, and helical winding.
Autoclave: Bag molding is another name for autoclave molding. It entails compacting the reinforcement and resin on a stiff mold, then passing it through an elastic, flexible membrane to form a tight bag with the tooling. The mold is put in a confined chamber with a few megapascals of internal pressure. This pressure is given to the membrane by a fluid (air, water, nitrogen, or steam), which aids in resin polymerization.
Simultaneous spray molding: This method evolved from the contact molding procedure. Molding is done by spraying chopped fibers combined with catalyzed resin onto a waxed mold at the same time. A roller is then used to condense the sprayed layer and eliminate bubbles. This technology allows for the low-cost production of medium and large parts as well as basic forms. However, because this form of molding solely employs chopped fibers, the pieces produced have poor mechanical qualities.
Different procedures of fabrication for polymer composites-based fibers.
According to studies, the constraints of each technique and the production parameters employed during composite processing might induce undesired internal flaws into the material, such as bubbles or cavities, poor or rich areas, delamination, shrinkage, and so on [30]. As a result, these flaws can compromise the mechanical characteristics of composite materials. Several investigations on carbon and glass reinforced composites have been conducted. Liu et al. investigated the influence of autoclave pressure cycling on the porosity of a [0/90]3 s carbon/epoxy cross-linked composite. In comparison to tensile strength and modulus, they demonstrated a considerable sensitivity to porosity in the interlaminar shear strength and flexural parameters of the composites. They discovered that when the porosity inside the composites is less than 4%, the interlaminar shear strength reduces by roughly 8% for every 1% increase in porosity [31]. Gu et al. investigated void formation by transforming hygroscopic water absorbed by glass and carbon fibers, as well as trapped air, into vapor bubbles as a result of the temperature rise during the thermocompression process [6]. Compared to synthetic fibers, the problems associated with the processing of plant fiber composites are more complicated due to the particular characteristics of this type of fiber. The use of plant fibers for resin reinforcement necessitates careful consideration of the production conditions. The essential criteria for regulating the thermal deterioration of the fibers are the process temperature and time. To reduce viscosity, the hot-molding temperature must be higher than the melting point of the resin, and the time must be long enough to allow the molten resin to permeate the fibers, assuring good adhesion between the reinforcement and the matrix. In conflict with these needs, the melting temperature and time should be as low as possible to slow down the thermal deformations that occur and cause fissures and permanent damage to the fibers, as well as the pectin breakdown, which begins at 180°C [32, 33].
E-glass fibers are commonly used as reinforcements in shipbuilding, while carbon fibers saturated with epoxy resin are commonly used in aeronautics. The use of synthetic fibers in composites is supported by their high chemical resistance, compatibility with most impregnation resins, and mechanical and thermal performance. However, the usage of this sort of reinforcement is no longer adequate: On the one hand, their comparatively large density penalizes them; on the other hand, they endanger the health and the environment. Since the 1980s, these environmental problems have become a major concern for our society and the media. And since then, the industrial optimization of eco-composites is booming thanks to their high specific mechanical properties. The limits of applications are constantly being pushed back through the development of fiber preforms and the adaptation of processing methods.
Automobile body sections, such as engine hoods, dashboards, and storage tanks, are made using natural fiber reinforcements such as flax, hemp, jute, sisal, and ramie. The VARTM manufacturing technology was used for these composite constructions, and its liability was tested through structural testing and impact stress analysis. As a consequence, the material’s weight was reduced while its stability and strength were improved. The increase in safety characteristics was tested using the head impact criterion (HIC), and it was discovered that composite constructions with natural fiber reinforcements are appropriate for automotive body sections [34, 35, 36]. Figure 5 depicts the external body elements of a Volkswagen x11 crazy carbon fiber replica.
Volkswagen xl1 carbon fiber body pieces, adapted from [
The automobile sector, in particular, has shown a genuine commitment to economic and environmental concerns by using natural fibers in different non-structural components (dashboards, door panels, spare wheel covers, etc.) with the goals of lowering mass, fuel consumption, and emissions (Figure 5).
Fiber-reinforced epoxy composites manifest the properties required for aircraft interior panels, such as resistance to heat and flame and disposal of materials. Fiber-reinforced epoxy composite shows a variety of applications in the aerospace industry due to its superior mechanical properties and lightweight structure. Conductive fibers in the layer of fiber composite structure eliminate the requirement of separate wires for transceivers of communication devices. High stiffness with a lower coefficient of thermal expansion is achieved when P100 graphite fibers diffused in 6061 aluminum matrix composite material are employed to the high gain antenna of the Hubble space telescope [37].
For example, the wing of the plane is a composite material, the fiber is carbon fiber and the resin is epoxy. The manufacturing technique involves resin infusion: all the reinforcing fibers are dried, shaped and then the resin is infused into the reinforcement. The choice of polymer matrix must both ensure good performance for the finished wing after curing and also maintain a well-tuned reactivity, not too high to allow the wing to be infused, which can take several hours, but enough to allow the reactions to take place effectively.
Components and structures functioning in the marine environment are subjected to significant stresses caused by wind, waves, and tides. Furthermore, they must endure hostile and harsh environmental conditions throughout their lives, including being placed in the splash zone if not submerged in seawater. The use of polymer composites in maritime systems has been the subject of much research in recent decades, showing the potential benefits of replacing various components such as ship hulls, propeller blades, wind, and tidal turbine blades, to name a few [38]. For example, in the offshore construction (seawater piping, stairways and walkways, firewater piping, grating, fire and blast walls, cables and ropes, storage vessels, and so on), valves and strainers, fans and blowers, propeller vanes, gear cases, condenser shells, and so on.
And more other applications, which we will not be able to represent all of them such as:
Civil engineering includes the construction of new advanced structures (roofs, plate and shell elements, linear elements, pipes and tanks, folded structures, and so on) as well as the rehabilitation of existing metallic and concrete structures such as buildings, bridges, pipelines, masonry construction, and so on.
Sporting goods: Golf club shafts, tennis rackets, bicycle frames, fishing rods, and so forth.
Electrical and electronic components include power line insulators, fiber optics tensile members, lighting poles, and so on.
Chemical Industries: stacked bottles for fire departments, composite containers for substances, mountain climbing, ducts and stacks, subterranean storage tanks, and so on.
Medical field: Orthopedic medicine, prosthetic devices, and imaging (MRI).
Understanding the significant material characteristics of fiber/epoxy constituents, as well as the fundamental structures and availability of production technologies, is required for the use of fiber/epoxy composites in a range of applications.
Furthermore, the manufacturing technique used has an effect on the ultimate qualities of the material. The cost of materials is influenced by production volume—the bigger the volume of production, the lower the cost of materials. In the instance of the car industry, increasing production volume increases the risk of investing in raw materials while building manufacturing set-up based on production rate and cycle time. In addition, the product’s design complexity increases the cycle time, decreasing the manufacturing pace.
On fiber-reinforced composite manufacturing, current progress, novel advancements, and future research prospects are summarized and presented. However, the ongoing demand for composite constructions necessitates a large consumption of environmentally hazardous components. Certain fibers (for example, carbon fibers) utilized to improve qualities in numerous sectors are a significant hindrance to recycling at the end of the composites’ life. As a result, the current environmental crisis, which has reached a tipping point, necessitates immediate and objective action to cut greenhouse gas emissions. As a result, obtaining advanced composites from renewable energy resources would be the best ecological answer. Furthermore, future research areas might focus on recycling current composites into high-value alternative goods. Furthermore, new innovative methods for post-consumer waste treatment must be developed. Additionally, new sophisticated technologies for post-consumer waste treatment must be developed, or existing FRP composite production technologies must be improved.
The authors declare no conflict of interest.
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Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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