Introduction to Alginate: Biocompatible, Biodegradable, Antimicrobial Nature and Various Applications

Abstract

Alginate is a polysaccharide that has found numerous applications in the domain of pharmaceutical science, paper and textile industry, food industry, dental applications, welding roads, mucoadhesive properties, scaffolding, biomedical and engineering due to its cost-effective nature, film forming ability, gelling, biocompatibility, biodegradability, nontoxic, non-immunogenic, readily availability, antimicrobial nature. Hydrogels of alginates play a crucial role in well-controlled or sustained release drug delivery, wound healing, and tissue engineering. This book chapter will provide a detailed overview of Alginate and its applications. To the best of our knowledge there no such type of informative data is available on Alginate and its relation with drug susceptibility. Here we more focused on the antibiotic capability of Alginate and its association with bacterial resistance.

1. Introduction

Alginate is a polysaccharide distributed widely in the cell wall of brown algae, including Laminaria and Ascophyllum species. Polysaccharides are made of several repeating units of monosaccharides, which decide the overall structure and properties of a cell. The Alginate is often chemically reacted with water to make various gum pastes, ideal for creating molds of dental impressions, hands, feet, or other small-scale items [1]. Alginate contains a unique property to hold upwards of 200 to 300 times its own weight in water, making it a naturally gelling substance. The Alginate can adapt to the helpful thickness to perform applications – making it a diverse product for use, thickening or pharmaceutical, development of medicine & medical application. In the field of treatment, a broad range of polysaccharides are being used, while biodegradable polysaccharides are more useful [1, 2]. Brown algae are synthesized primarily of alginates, a carbohydrate polymer present in the form of a water-insoluble composition of magnesium, sodium, potassium, and calcium salts of alginic acid that are all structural participants of brown seaweed cell walls. They are all structural participants that react as unbranched binary polymers made up of 1,4 bonds between b-d-Mannuronic (M) and a-1-Glucuronic (G) acids [2]. The alginates composition is based on the source and varies with G: M ratio. This is also be altered in wide varieties by varying molecular weight, G: M ratio, particle form, volume fraction, and cation availability. Researcher Edward Stanford first used alginates in 1883, and development at the commercial level commenced in 1927 [2, 3]. Alginate production worldwide has now risen to about forty-one tonnes per annum. Pharmaceutical, food, cosmetic and dental industries are extensively used alginates. In the current scenario, the medicine, dental, and pharma industries have become incredibly influential in biomolecules, especially alginates [4]. Alginate has a well-known identity and applications in the domain of pharma industries for its special appearance in drug delivery, wound healing, dermatology, and scaffolds because of their nature, including natural disintegration, gel formation, biocompatibility, and nontoxic [4]. Alginate is act as the natural gum that has an benefit over biosynthetic polymers because they make hydrogels, are readily accessible, and are cost-effective. Alginate can be orally administered into the body in a less invasive manner, enabling a wide range of medical applications. Alginate gels are useful for cell transplantation and tissue engineering to replace organs in patients who have lost or failed organs or tissue [5].

2. Alginate properties

Laminaria hyperbola, Laminaria Digitata, Laminaria japonica, Ascophyllum nodosum, and Macrocystis pyrifera are all well-known stains of brown algae obtained from seaweeds, which are responsible for making commercially available alginates [5, 6]. In general, alginates have water-insoluble properties; they are washed, crushed, dried, powdered, and treated with the basic compounds, especially NaOH or KOH, to make sodium/potassium salt of alginic acid, which is water soluble. Alginic acid, in other words, known as algin, occurs naturally in edible carbohydrates found in brown algae. It has hydrophilic nature and makes a viscous gum when hydrated [7]. With metals such as sodium and calcium, its salts are called alginates. Its color ranges from white to yellowish brown. Sodium alginate and alginic acid of sodium salt are the famous names of alginates in the market, and it is available with these two names. Alginic acid is a crucial component of the biofilms produced by Pseudomonas aeruginosa [8, 9]. Alginate’s acidic behavior makes them an appropriate biodegradable biopolymeric product in biomedical and pharmaceutical applications. Because of their acid behavior, alginates make gels due to the presence of Guluronic acid (G) monomer in alginates within a less time period, especially the presence of Ca2+ ions [10]. This feature of gelling permitted Alginate to possess wide range applications, including encapsulation of various fragments or even cells interior of alginate matrix along with very less cons. The alginates have a carboxylic group for numerous applications and can be modified based on the application [11]. Exopolysaccharide forms of alginates are present within Pseudomonas and Azotobacter bacteria [11, 12]. These two bacterial classes are very potent alginate producers, can synthesize alginates with particular monomer formulations, and may be capable of producing ‘tailor-made’ bacterial alginates using recombinant DNA technology and engineering in protein.

2.1 Structure and characterization

Alginates are a member of the unbranched biopolymer family. The alginates contain 1,4-ß-D-mannuronic acid (M) and 1,4 α-L- guluronic acid (G) monomers, with a homogenous (poly-G, Poly) or heterogenous (MG) block combination that is proven by partial acid hydrolysis [13]. Alginates are available in different locations of a sea bed and have different molecular weights ranging between fifty thousand and five lakhs. Different parts of seaweed contain different types and quantities of Alginate in their cell walls [14]. Alginates are provided a flexible, mechanical structure to the seaweeds and cushion them from possible inflammation when the seaweeds are subjected to strong water motion. Alginate viscosity is always PH responsive, and increment in viscosity is the principal signature of decrement in pH and reaches a pH ~3.5 because carboxylic groups in Guluronic acid is the part of the alginate structure protonated and make hydrogen bonds [15, 16]. Alginates may deal with different molecular weights depending upon the requirement to analyze the pre-gel viscosity of the solution or post-gelling distribution strength in a separate manner. The viscosity of the solution is maintained by a mixture of high and low-molecular-weight alginate polymers [16].

2.2 Molecular weight and solubility

The molecular weight of sodium alginate ranges between 32,000 and 400,000 g/mol on the commercial level. Alginate deals with a broad range of solubilities due to its different molecular weights [17]. The alginates are insoluble in water (H20) because it contains a terminal carboxylic ion (-COO-), so these cations make bonds to this and yield a not water-soluble product, and alginates with divalent or trivalent cations also are water insoluble [18]. Salts of alginic acid with monovalent cations, including Na-salt, K-salt, NH4-salt as well as propylene glycol alginate, are all soluble in hot and cold water. Sodium alginate is present within the cell wall of marine brown algae and contains 30 to 60% alginic acid approximately [19]. The transformation of alginic acid to sodium alginate permits its Solubility in water, which assists in its extraction. Alginate can absorb body fluids and H20 up to 20 times its weight, resulting in a hydrophilic gel.

2.3 Biocompatibility

Alginate biocompatibility varies at the level of its purity and has been extensively evaluated in-vivo as well as in-vitro. Alginate is a naturally occurring anionic polysaccharide typically extracted from brown seaweed and has been extensively investigated and used for many purposes due to its biocompatibility and mild gelation by the addition of divalent cations such as Ca2+ [20]. The composition of Alginate defines the level of purity and degree of biocompatibility of Alginate. Biocompatibility has been reported that Alginate containing a high number of M monomers is more immunogenic in nature and 10 times more strongly promoting cytokine biosynthesis in the comparison of G monomer in alginates but apart from this, reported very less response or no immune response across alginate implants [21]. Impurities of alginates, including heavy metals, endotoxins, proteins, and polyphenolic compounds, can cause a variable reaction at the implantation or injection sites. In contrast, not huge serious tissue injury or inflammatory cases were reported in alginates obtained from branded or reputed companies, commercially available or certified [22].

2.4 Alginate derivatives

Various alginate derivates have been reported to date and are useful in the range of biomedical and pharmaceutical applications. Derivatives of Alginate with amphiphilic nature have been synthesized by introducing non-water-resistant moieties (e.g., alkyl chains, non-water-resistant polymers) to the backbone of Alginate [23]. These derivatives are capable of forming self-organized structures, include particles and gels in aqueous media, and are also useful for drug delivery applications. Sodium alginate amphiphilic derivatives have been made by the conjugation of long alkyl chains to the alginate backbone via ester bond formation [24]. Dodecyl or octadecyl is an example of long-chain alkyl groups that form bonds with the alginates matrix via esterification. Rheology, gelling and crosslinking properties are much needed for bone regeneration and cartilage repair [25]. Drug delivery sustained or controlled vehicles are obtained from Alginate derived from Poly butyl methacrylate. Alginate also has peptides with cell adhesive peptides made by adding peptides as side chains and joints together with carboxylic groups of sugar residues [25, 26]. Derivatives of Alginate containing cell adhesive peptides have been gaining scientific applications in human health. These derivates are synthesized by chemically introducing peptides as side chains. Sodium alginate (NaC6H7O6) is made from the sodium salt of alginic acid, and potassium alginate (KC6H7O6) is the potassium salt of alginic acid [27]. Calcium alginate (CaC12H14O12) is derived from sodium alginate, and during calcium alginate synthesis, sodium ions are replaced with calcium by the ion exchange process.

2.5 Alginate gelling properties

Alginates form gels by reaction with divalent cations, including Ca2+; the exchange of sodium ions from glucuronic acids with divalent cations in solution is the crucial factor for gelation and crosslinking of Alginate [28]. Gelation is an important property of Alginate, and it is induced by Ca2+. The gelation phenomena are well known, reported as an egg-box model, and intensively studied in the last five decades. Alginate gel formation is affected by many factors, including the concentration of reactant, heating temperature, pH, and salts [29]. These factors are decided gel strength and rheological properties, including viscosity, storage, and loss moduli of the gel. Sodium alginate is a gelling and thickening agent in the presence of calcium that forms stable heat gels; calcium ions are chemically reacted with the G monomer present in sodium alginate structure to crosslink with another molecule [30, 31]. EDTA sodium citrate or monovalent ions complex ions (phosphate and citrate) are potent complex-forming agents that have a high chemical affinity to Ca2+, which can disrupt calcium alginate gel in an easy manner. The appearance of non-gelling ions (Na + and Mg2+) in high concentrations also participates to instability [32]. Alginate is only forms gels when chemically reacted with divalent ions (Ca2+, Sr2+, and Ba2+) or trivalent ions (Fe3+ and AI3+) ions. Divalent and trivalent ions have been explored for the fabrication of carriers for the well-controlled and sustained release delivery of drugs [33]. This is happened due to ionic interactions and intramolecular bond formation that are present within carboxylic acid groups on the polymer matrix. Alginate is a combination of two uronic acids; each unit of uronic acid includes a negatively charged carboxyl group of high ionic exchange capacity, these units form chains, which create the polymer structure of Alginate [34, 35, 36]. The molecules of Alginate in an aqueous solution push away from each other by electrostatic repulsion forming a smooth viscous liquid. When calcium ions are added with negatively charged Alginate, molecules attract positively charged calcium ions forming a salt [36]. When will further add positive charge, calcium ions with negatively charged Alginate make contact with other alginate molecules and become linked by a calcium ion. This phenomenon is known as “egg box junction” After its visual similarity to an egg in an egg carton. This reaction occurs instantly throughout the solution, and alginate gels come in contact with calcium ions [37, 38]. When an aqueous solution of sodium alginate is added dropwise to an aqueous solution of calcium salt and gels instantly, wherever it comes into contact with calcium ions aqueous solution of sodium alginate forms beads as it gels due to surface tension creating a jelly by controlling ionization of calcium [39]. It is possible to gel the entire solution into any desired shape; this process is called the ion control method. According to the ion control method, calcium ions are first sequestered, and Alginate cannot react chemically with them; sequestered calcium does not react chemically with aqueous alginate solution, then it mixes uniformly in the solution [40]. The pH of a solution is gradually reduced sequestered calcium becomes released, reacting with alginate solution gels uniformly. Calcium reacts as a sequestering agent and a pH reduction agent by varying the type and quantity of these two types of agents the time required for gelation can be freely adjusted from as little as a few minutes to an overnight process [41]. Making use of this property, Alginate is used as a gelling agent in a wide range of medical and pharmaceutical applications.

2.6 Effect of pH on alginates

The Alginate’s water solubility is effected by parameters including pH and ionic strength. Alginates have not so much water solubility with further down pH values caused by the deprotonation of carboxylic groups (-COO-) [42]. The alginates viscosity is constant above pH > 5. Although in solutions containing pH < 5, the COO- group in attendance in alginates will get protonated to COOH, and then electrostatic repulsion will decrease between chains [42, 43]. They can proceed together near to make hydrogen bonds, by which measures a decrease in viscosity. It has been pH > 11 reported alginates viscosity is decreased due to de-polymerization. The crosslinking is influenced by the concentration of an ionic solution, which is capable of increasing in viscosity and molecular weight of alginates [44]. Furthermore, the crosslinking depends upon G monomer confirmation and M groups present in the matrix of Alginate. Pawar and Edgar, in 2012, reported the compounds synthesized from sodium alginate and observed it to be stable between pH 5 to 10 [1, 44].

2.7 Sterilization

The viscosity of Alginate decreases with autoclave sterilization because autoclave heating is responsible for randomly breaking alginate chains. It means autoclave sterilization is not favorable for Alginate [45, 46]. The value to which this loss occurs is measured by the appearance of other kinds of components in the solution. Gamma radiation and ethylene oxide are important for alginate solution sterilization without any disadvantages [46]. Alginate sterilization is important for the removal and overcoming of contamination from alginate solution before use.

2.8 Immunogenicity

Drug delivery in control or sustained release manner is the latest trend of pharmaceutical dosage forms requirements for proper application in drug vehicles; alginates play a crucial role because of their immunogenicity and biocompatibility [47]. Chemical composition and mitogenic pollutants are two factors responsible for alginate immunogenicity. When Alginate makes contact with blood, it is believed to have decreased hemolysis and mild cytotoxic effects. Alginate is an example of a weak immunogen, but the immune responses produced by Alginate are very effective or strong in killing pseudomonas bacteria [47, 48]. SLN is important to increase the alginate immunogenicity; SLN is useful in drug delivery and can prolonged boost effectiveness. The SLN-Alginate conjugate is better at stimulating the immune system to produce a high number of immunoglobulins with effective outcomes compared to Alginate antigen alone; this is proven by the results of ELISA and opsonophagocytosis tests. The challenge experiment also reported that the Alg-SLN-treated mice showed a higher level of immunity in comparison of mice treated with pure Alginate against infections caused by pseudomonas aeruginosa [48]. Overall results show the efficacy of the newly synthesized vaccine to induce immunogenicity, and therefore it will be considered a candidate for a strong vaccine against pseudomonas aeruginosa.

2.9 Bioadhesion

Bioadhesion and mucoadhesion is the phenomenon through which natural and synthetic macromolecules stick fast to mucosal surfaces in the body. If these materials are then included into formulations, drug soaking up by mucosal cells may be increase or the drug released at the site for an make larger period of time [49]. The Carboxyl group of Alginates has a mucoadhesive anionic polymeric layer and represents mucoadhesive properties. In the comparison of polycation or non-ionic polymers, polyanion polymers have more efficient bioadhesive properties. Alginate contains better mucoadhesive strength in compared to polymers, including Polystyrene, Chitosan, Carboxymethyl cellulose, and Poly (lactic acid) [50]. The mucoadhesive properties of Alginate play a crucial role as a mucosal drug delivery vehicle to the GI tract and nasopharynx by extending drug residence time at the site of, making them more effective. Alginate is widely used as a bioadhesive for its biodegradability and biocompatibility properties and it undergoes electrostatic interactions with positively charged compounds [51, 52]. Alginate bioadhesive systems provide intimate contact between a dosage form and the absorbing tissue, which may result in high concentration in a local area and hence high drug flux through the absorbing tissue.

2.10 Toxicity

Alginates are reported nontoxic according to plenty of studies and crosslinked with sodium/calcium are nontoxic to cells, even not harmful for eyes and skin. While, Alginate due to its nontoxic nature found various applications in fully controlled and sustained release drug delivery, biomedical, cosmetics, food industry, paper and pulp industries [53]. Sodium alginate is perfectly safe and nontoxic for using as additive in food products. As sodium alginate is widely known as nontoxic, there is no limit on the amount consumed.

2.11 Biodegradation of alginate

In mammal’s Alginate is inherently non-degradable due to lack of the alginase enzyme, which is responsible to cleave the polymer chains. To make Alginate degradable in physiological environment includes partial oxidation of alginate chains [54]. Alginate oxidized form can degrade in aqueous medium and these materials are use as drug delivery vehicle and cells for numerous uses [55]. Sodium periodate is able to oxidized Alginate. Periodate oxidation breaks the carbon-carbon bond of cis-diol group which is present in uronate residue and form an alteration in chair conformation to an open-chain adduct, which is not able to degrade alginate backbone [56]. A slight change in molecular weight of Alginate during oxidation is expected. Adjusting of molecular weight distribution of Alginate can be play a crucial role in decupling of degradation rate and mechanical properties of alginate gels. Partially oxidized alginates have been formed binary alginate gels with low and high molecular weights through either ionic or covalent cross linking [57].

3. Applications

Alginate has very wide range of applications include rate controlling experiments in drug delivery systems, a matrix for biomolecules and excipients in biopharmaceutical growth and development for local administration biomedical engineering. Alginates can be exclusively employed in food additives and drug formulations because of their nontoxic nature which is demonstrated in Figure 1.

Figure 1.

Application of alginates in pharmaceuticals, food and biomedical engineering fields [56, 57].

3.1 Pharmaceuticals and food

Alginates are playing conventional role in pharmaceuticals includes serving as gel forming, thickening and stabilizing agents, as Alginate can play crucial role in sustained release drug products [58]. In the present medical domain, various medicines or drugs administered to patients are providing a wide range of side effects. Oral drugs are majority recurrent use of alginates in pharma applications, however use of alginate hydrogels as storing place for tissue confine drug delivery is growing [59]. Alginate gels are investigated for delivery of wide range of low molecular weight drugs and are very applicable at the moment that a primary or secondary linkage between drug and Alginate can be utilized to initiated kinetics of drug release [60]. Typically, alginate gel is nonporous, regulating rapid diffusion of small molecules through the gel.

3.1.1 Controlled drug delivery

In general, the structure of alginates gels is containing pore size (~5 nm) assist to fill this space by low molecular weight drugs through each of two chemical or physical bonding. When a loaded drug comes in association of an watered environment, the drug release is controlled [61]. Furthermore, the loaded drug porters are water dissoluble and may g0 through degradation in an watered medium, consequently crosslinking alginates with bivalent or trivalent cation will increase the strength of the gels or films.

These belongings help researchers to study the kinetics of drug release. The sodium salt of alginic acid and polyethylene oxide blends are described for controlled release of Valganciclovir HCL in vitro, as an anti-HIV drug [61, 63]. Tablets and capsules are the potent exemplification of ordinary oral drug dosage forms and can be prepared into immediate release systems for implementation rapid absorption of the drug. The diagrammatic representations showing in Figure 2. The release amount of the drug can be retarded by the coating of rapid release systems. For this type of coating, alginates are broadly used. For rapid release dosage forms, alginic acid is play an important role for tablet as a disintegrant and sodium alginate can be used as a tablet binding agent [64, 65]. The drug dosages forms are released in a controlled manner from formulation by using a physical or chemical barrier. In the case of oral dosage forms, the barrier can made using different techniques including coating of active agent or entrapment of active agent into polymer matrix [62]. For the design of dosage forms like immediate release system and sustained release system, the alginate is commonly used. The given Table 1 shows alginate based carrier containing active substances and there applications.

Figure 2.

Oral drug delivery using alginate nanoparticles [61, 62].

Carrier system	Material	Active substances	Applications	References
Alginate hydrogels	Zinc oxide	Loaded with curcumin	Extended adobe time of curcumin interested in gastrointestinal domain.	[29, 36]
Films	Sodium alginate	Amoxicillin	Used as a bone substitute	[37, 38]
Nanoparticles	Calcium alginate	Encapsulated with collagen peptide chelated calcium	Used in the development of calcium absorption.	[40]
Tablets	Sodium alginate	Mesalazine	Used in the treatment of Cohn’s disease in large intestine	[45, 46]
Liposome	Sodium alginate	Cisplatin	Used in targeted therapy for ovarian carcinoma	[50]
Microsphere	Sodium alginate as a hyperbolic polymer	Theophylline	Provided sustained release of drug	[61, 63]
Microcapsules	Calcium alginate	UFV-AREGI bacteriophage	Controlled action of cell	[62]

Table 1.

Alginate based carrier systems containing active substances and their applications.

3.1.2 Food industry

In food industry, restructured foods are manufactured with different shape and size by improving the texture, esthetic and structural properties, which provide the novelty in product to meet demands of consumers [66]. Alginate is approved by FAO/WHO as a safest food additive because of its unique food applications. Alginate is used in various of food products include ice cream toppings, fruit jams, jelly, milk products, food packing, instant noodles, beer etc. [67]. Alginates are important for stability of food products under low and high temperatures. Gelation rate and gel strength of alginates are control by concentration of Ca2+ and H+ in solution [68]. In the current scenario the growth and development of alginate-based food packaging has been carried out. In the case of short-term packaging biodegradable and renewable biopolymers are widely used. For long term storage purpose bioactive agents are merge with alginate films could be released to overcome lipid oxidation, microbial growth in foods and also enhances their self-life [69]. The alginates films synthesized through incorporating cottonseed by-product, biologically active protein hydrolysate contains good antimicrobial and antioxidant properties of lipids and pH adjustment increase their visible light and lipid barrier properties [69, 70]. Some natural and chemical additives are essential for the protection of food materials, these additives are enhance functional, mechanical, nutritional properties of food products. Alginates are useful in ice cream industry employed as a gelling agent, thickening agent and stabilizing agent. Alginate overcomes the syneresis and provides freeze/thaw stability to bakery creams. It also gives desirable melting characteristics, overcomes shrinkage, crystal formation and enhance heat shock resistance [70].

3.1.3 Protein delivery

Alginates are playing crucial role in entrapment of protein drug because it overcome or avoid the denaturation and can protect from deterioration until their release. Alginate gels can also be controlled the rate of release of protein [71]. Alginate hydrogels reversible binds with heparin binding growth factors include vascular endothelial growth factor or fibroblast growth factor and lead to the sustained release due to its adaptable property [71]. Highly polydispersed index proteins, include lysosome and chymotrypsin, are successfully cross linked with alginate microsphere. The sodium alginate is useful for cross linking and constant release system.

3.1.4 Cell delivery

The arginine glycine aspartic acid peptides (RGD) contain alginate gel has been employed in vitro cell culture due to their non-immunogenicity, biocompatibility and ease of administration in the body [72]. RGD peptides in alginate gel is responsible for the improvement of phenotypes of interacting myoblasts, chondrocytes, osteoblasts, ovarian follicles and include bone marrow stromal cells. Chemical fusion is responsible for enhancement in adhesion and proliferation of RGD peptides to the alginate backbone, in disparity with non-modified Alginate [72, 73]. Density of RGD in gels is an important factor for growth and cell adherence number. Cellular responses can be persuade by fluctuation in length of spacer arm between RGD peptide and alginate chain.

3.1.5 Wound dressing

Alginate based wound dressing provides numerous advantages over the gauge [74]. The presence of pathogens into wound can be inhibited by keeping wound in dry condition, whereas moist wound form provided by dressing with Alginate makes it easier in wound healings [74, 75]. Silver with Alginate in wound dressing can be increased antimicrobial activity and antioxidant property of Alginate, which leads to improvement in binding affinity for elastases, matrix metalloproteases-2 and proinflammatory cytokines or immune regulators (TNF-α, IL-8) [75]. Established on scaffolds alginate polyethylene glycol, methyl ether methacrylate and M. oleifera, aloe vera with wound healing property is prepared by using alginate treated calcium ions (Ca²⁺) this is responsible of the development of an egg box structure due to interconnection between calcium and guluronate blocks of alginate [76]. Because of its bad integrity for tissue scaffolding, it guide to handling and stability problems [77]. Therefore, to solve this trouble, plasticization can be introduced, which is overcome the intermolecular attraction forces in between polymer chains by maintaining alginate plasticizer ratio. As a outcome, it guide to an development in the handling and stability of alginate. Handling and stability problems can be solved by addition of plasticizer including polyethylene glycol, methyl ether methacrylate in optimum ratio [78].

3.2 Alginates in cosmetics

Researchers have been researching alginates for long time to make high quality products in cosmetic industry domain that provide unique benefits to skin. Alginates are capable to absorb UV rays, overcome sun’s harmful effects, act as a moisturizer of epidermis, skin smoothening and make sure small cells renewal [79]. Alginates are reported for gel formation can thicken and maintain moisture, are useful for varieties of cosmetics products. Due to gel forming nature, alginate assists in the retention of lipstick color on lips and body lotion moisturizers as well as face creams [80]. To make demandable all round body lotions, alginate act a natural thickener agent is incorporated in sunflower wax. Alginates are an example of natural polysaccharide that contained a very high viscosity and has a strong water absorption potential. Alginates viscosity can be optimized to make sure maximum viscosity [81]. Alginates are explored for face masks and antiaging masks which slow down wrinkles and lift the skin, even aging process. Also, alginates are useful in Dentures which removable set of replacement teeth and gum tissue with complete backing and attractive appearance [82]. Alginates application in dentures are a removable set of restorative dentistry and gum tissues that can provide us with both complete backing and beautiful appearance even at older age.

3.3 Textile industry

Substrates for color paste can prepare using textile grade alginates in use of design in print fabrics, shawls, towels and extensive range of textile products. Alginates are used as a cleaner and easier to decompose substrate for textile printing compared with other substrates [83]. Alginates can use in printing cotton, jute, and rayon allows for easier handing out of wastewater. Sodium alginates can use as a thickeners in textile industry for purpose of printing to thicken dye paste. Screen roller printing instruments may be used to apply the pastes to cloth. Alginates became general thickeners with the discovery of reactive dyes. Cellulose content of clothes is chemically reacted with these substances. Many famous thickeners, including starch, chemically respond to reactive dyes, resulting in lower color yields and sometimes difficult to wash out by products [84]. Alginates can act as a strongest thickeners for reactive dyes because they non-reactive with dyes and rapidly washout from the finished textile. In traditional screen roller printing the alginate of medium used to high viscosity, although in modern high speed roller printers even low viscosity alginates are giving very attractive printing [84].

3.4 Welding rods

Welding is very famous and useful technique to making all kind of structures with metals. In the welding procedure coating is used as a flux and to detection of situations near the weld including temperature, oxygen and hydrogen [85]. In this instance, sodium silicate can mix with dry coating ingredients to give some of plasticity requires for coating extrusion into rod and to tie dried coating to the rod. The silicate, in the other side, neither binds nor giving adequate lubrication to allowed to successfully and smooth extrusion [86]. A lubricant and a binder have need of to keep the damp mass together before extrusion and to hold on to coating on rod in from throughout drying and baking. To achieve these standards, alginates can use.

3.5 Alginates used in animal feeds

Alginate salts of sodium and potassium can widely use as industrial substances including emulsifiers, stabilizers, thickeners, gelling agents, and binders. There is no capable authority possesses recommended usage of sodium alginate in feeding stuffs for dogs, other non-food producing animals, and fish [87]. Whereas potassium alginate can use for feed in cat and dog as food. The alginates are useful for the fish feed has no bad effect on the consumer. Alginate can provide little bit irritating to eyes but not to skin [88]. The application or appearance of these ingredients in fish feed poses no bad effect to aquatic environment. A gel type livestock feed mixtures are made up by mixing feed nutrients, water, alginate, and a water insoluble calcium content from reacting with alginate [89]. The calcium component is soluble in water or the sequestrate affecting reactivity between alginate and calcium component is extracted after the feed mixture is formed, resulting in a gel feed containing the feed nutrient ingredients [90]. The livestock can then be fed the gel meal.

3.6 Biotechnological applications

The Alginate provides a solid support through matrix shields incorporating biological agents via immobilization from chemical and physical agents initiates protection of microbial cells opposite various atmospheric conditions of reaction media include pH, temperature and shear stress [91]. There are very wide applications of immobilized cells compared to those of free cells in biotechnological processes. Microfluidic are very famous technique to immobilized microbial cells within micrometric and monodisperse particles, which is applicable in bioprocessing advancement [91, 92]. Microorganisms, mammalian cells and proteins are immobilized by alginate microparticle. Cell isolation, cellular reaction to different stimuli and cell division techniques has been inspected by immobilization of cells through a microfluidic method. At high alkaline pH, lipase enzyme biosynthesized by Bacillus subtilis through submerged fermentation process be visible good thermal stability and enzymatic activity [91, 92, 93]. However, when Bacillus subtilis is immobilized in alginate microparticles through microfluidic method, increases lipase production when immersed in the bioreactor. The non-desirable turbidity in final product of industrial processed fruit-based beverages is one of the huge problems, the reason behind this problem is presence of inner cell walls of the polysaccharide including pectin, cellulose, hemicellulose, starch and lignin particulate suspension [94]. In fruit juices pectin are responsible to cause turbidity, and unwanted solid suspension can be degraded and removed by employing enzyme pectinase.

3.7 Environmental applications

Adsorption technique is more reliable technique for the treatment of environmental contamination. The pollution control in water and waste water including heavy metals, industrial dyes, pesticides and antibiotics etc. can be removed by assistance of alginate-based composites, which is considered as the most effective adsorbent [95]. Alginates are carboxyl and hydroxyl groups rich, thus capable to targeting pollutants including heavy metals and dyes by arresting metallic or cationic ions via ion exchange by cation cross linking. The limitations of alginate gels are poor mechanical properties, elasticity, high rigidity and fragility [96]. To overcome these limitations, organic and inorganic alginate-based composite have been synthesized in proper manner.

3.8 Liposomes

Liposomes are the biodegradable and biocompatible carriers with biological cell membrane properties and these possess intensive delivering property as exposed in newly accepted marketable products [97]. Liposome is reported as a novel drug delivery system for the delivery of pharmaceutical and biomedical products. They contain the ability to incorporate hydrophilic as well as lipophilic drugs due to their high flex. Liposome enhance the therapeutic index and improve the biodistribution of therapeutics [98]. Liposomes have wide variety of applications on top of free drug administrations, inclusive of treatment monitoring, diagnosis, and drug delivery. In case of their antitumor activity of chemotherapeutic agents, the drug loaded liposome is accumulated on the tumor site because of their increased permeability and retention effect [99]. The toxicity of these agents has been reduce to non tumor tissues, and FDA approved numerous types of liposomes for cancer therapy.

3.9 Microspheres

Microspheres are small spherical structures, which are free flowing microparticles that have a particle size usually 1 μm to 1000 μm, commonly composed of protein and synthetic polymer. Microparticles are very useful for the controlled release of drugs, vaccines, antibiotics, and hormones. Microspheres contains large surface area and provides an easier evaluation of diffusion and mass transfer character [100]. Small molecules encapsulated by microsphere and command the controlled release of drugs within the body fluid. The utilization of sustained release drug system have proven to reward compared by way of traditional dosage forms, as they are free to overcome toxicity and make larger the effectiveness of the drug. Stability studies specified that Eudragit S-100 coated sodium alginate microspheres of naproxen sodium indicated constant a constant degradation rate of microspheres with 2 years shelf life of the formulation when it is accomplished under accelerated conditions and at room temperature [34].

3.10 Microcapsules

Microcapsules has interior core and exterior shell, which is combination of polymer liquid and solids, can be engulfed, which makes this delivery system for food and agriculture industry applications. Probiotics are use to treat gastrointestinal unevenness but are unsteady in gastrointestinal tract environment [101]. This problem is reduce by the use of double alginate coating microencapsulation of probiotics including Lactobacillus plantru and Lactobacillus casei. Microencapsulation enhance aliveness of probiotics in simulated gastric fluid, simulated intestinal fluid and also increases temperature resistance. Canthaxanthin is a functional pigment of Dietzia natronolimnea, and it is containing high antioxidant properties [102]. They are sensitive to light, oxygen, pH, and heat. Canthaxanthin is microencapsulated in alginate and alginates with high methoxy pectin promote retention in both neutral and acidic pH. These enhance antioxidant properties of canthaxanthin. Currently, the advanced technology of the insulin release system reported for the treatment of Type-1 diabetes mellitus [103]. Under this technology, hyaluronic easy to commercially available films are synthesized, and this decreases the thermal decay of alginate films in comparison of chitosan or starch films.

4. Conclusions

Alginate are found to have promising properties including mucoadesiveness, gelling, sol-gel transition and swelling characteristics. Owing to these advantages, they can hired in the system of controlled drug delivery or sustained release drug delivery and novel drug delivery systems including liposomes, microcapsules, microspheres, nanoparticles, hydrogels, metrices, membranes, tablets, cochleates and supersaturation drug delivery. Alginate has plenty of applications in the area of biotechnology (immobilization of biological agents), environmental contaminants treatments, biomedical (wound dressings, bone regeneration, neovascularization, cellular and protein), and pharmaceuticals (raft formulation, oral drug delivery, modulated systems, and controlled release structures). 3-dimensional cell cultures or tissue based on alginate are also being arranged and may be use to good advantage in drug development, research of compound cell physiology, and tissue engineering. Cell build nanoparticles for diagnostics and therapeutics in type-1 diabetes by porcine pancreatic islet cell encapsulation using monolayer cellular equipment technology is a latest approach being utilized with the use of alginates. A continuous challenge was on researchers to explore the possibility of modification of alginate by grafting with other low or high molecular wight polymers to improve its strength based on the need of the application.