Alginate and Its Use for Drug Delivery

Alginate is probably the most widely used biopolymer in the pharmaceutical and medical industries. This is due to its special encapsulation properties and role in wound healing. It was first isolated in the 1980s and since then it became a multifunctional compound in many applications. Thus, it is obtained at low cost and is a renewable and readily available, biodegradable, non-toxic, biocompatible, and, importantly, mucoadhesive and non-immunogenic compound [84]. It is recognized in the pharmaceutical industry as an excipient and is used to treat reflux esophagitis [85].

Structurally, alginate is a hidrosoluble polysaccharide formed from alternative blocks of 1–4 linked α-L-guluronic acid and β-D-mannuronic acid residues. It contains varying lengths of G-blocks, M-blocks, and/or MG/GM-blocks. High G content alginates have the ability to form stiffer, brittle, and more porous gels, but with increased strength, while high M content alginates tend to obtain more elastic and weaker gels [86].

Alginate is obtained from brown algae and is found as alginic acid sodium, calcium, and magnesium salts. The algae species used for the extraction of trading alginates are *Macrocystis pyrifera, Laminaria hyperborea, Saccharina japonica*, and *Ascophyllum nodosum*. It can be synthesized by various species of bacteria such as *Azotobacter vinelandii* and various *Pseudomonas* species, although they are not commercially available [72]. Alginate extraction is achieved by a relatively simple process. First, the raw material from the algae is ground and washed with acid followed by the extraction with hot alkali. The alginic acid is obtained after the extract has been filtered, precipitated with calcium, and acidified. The required salt form of alginate is obtained by treating insoluble alginic acid with metallic carbonates, oxides, or hydroxides [87]. Alginate biocompatibility has been extensively studied, with data showing that oral administration of alginate does not trigger many immune responses, in addition to the finding that it is non-toxic and biodegradable [88]. By contrast, intravenous administration of most commercial alginates can lead to adverse body reactions and fibrosis [89].

As an encapsulating agent, alginate was first used in the treatment of diabetes in the encapsulation of pancreatic islet cells [90]. Since then, it has been used for both macro and microencapsulation, and for other endocrine and recombinant cells for the release of therapeutic gene products such as growth hormones or human clotting factor IX (Table 2). It is also used in bioartificial organs such as they kidneys or for the protection of hepatocytes or parathyroids. Alginate gels cannot provide immunoprotection because they are too porous. Therefore, in most applications, alginate gels must be coated with cationic polymers of synthetic origin. For alginate-based coatings, the most used cationic polymers are poly-Llysine and poly-L-ornithine, but lately polyethylene glycol (PEG), glutaraldehyde, chitosan, and agarose have also been applied. Occasionally, other substances are used to reduce permeability, to ensure mechanical stability, and to increase the durability of the capsules; however, PEG remains the most used coating material. Another way to stabilize alginate gels is through the application of covalent crosslinking molecules, although this method of encapsulation interferes with the functional viability of the cells and can lead to cell toxicity [91].




Thus, based on its characteristics, alginate seems to be the most suitable biopolymer used for drug encapsulation (Table 2). This is due to its specific properties, especially as a matrix for controlled drug delivery devices. In addition, alginate is cheap and readily available, is accepted for consumption in quantum statis doses, is nontoxic, and ensures the protection of the mucous membranes of the upper gastrointestinal tract [101].
