Agar and Its Use for Drug Delivery

Agar is a long-chain biopolymer obtained from species of algae from the Rhodophyceae class, most commonly found in *Gelidium sp.* and *Gracilaria sp.* It represents the supporting structure of algae and is composed of a mixture of agarose and agaropectin, the gelling and the non-gelling fraction, respectively [125]. Agaropectin is usually removed during processing in order to obtain an agar powder with higher gel strength. Agarose is composed of repetitive units of D-galactose and 3-6, anhydro-L-galactose, linked by alternating α- (1 → 3) and β- (1 → 4) glycosidic bonds.

The ratio of agarose to agaropectin depends largely on seaweed growth, the environmental condition of seaweed growth, extraction methods, and rheological and gelling properties. These changes affect the final mechanical properties of the gels [126]. Agar quality can be significantly improved by modification, which is the most widely used chemical method. It involves hydroxypropylation, acetylation, etherification, and oxidation, the last one being the most commonly used [127]. Due to its gelling capacity, gel reversibility, and high hysteresis, agar is intensely used in various applications, mainly in the food industry, due to its ability to form gel and have an odorless taste. The most important agar evaluation index is gel strength, an important feature for pricing and developing new applications. The easiest way to improve agar characteristics is to remove the sulfate groups with hydrogen peroxide. Thus, after modification, the viscosity, ash content, and sulfate content decreased. Conversely, the gel strength, whiteness, and transparency increased after modification, in contrast to gelling, melting, and dissolving temperatures that decreased after modification [128]. Unlike other biopolymers, agar has been widely used as an encapsulating agent for probiotics since 1988 [129]. The method followed a simple way of encapsulation, which involves the use of drug microparticles and their dispersing at high temperatures in a hydrophilic liquid vehicle. After cooling, due to the transition to ambient temperature, the beads solidify. The same encapsulation method is currently used both for agar and other biopolymers used for this purpose [130]. The method depends on dropping a hot hydrophilic polymeric solution on the top of a cooled organic liquid, such as ethyl acetate which is a non-toxic compound, during which the polymer and the incorporated drug are insoluble. Usually, when only agar is used as an encapsulating agent, the release of the drug occurs in two phases. The first and faster phase leads to the release of 10–20% of the drug, based on the agar content of the beads. The second is a slower and more prolonged phase and becomes even slower as dissolution proceeds. In the first phase, the drug presents in a molecular state on the surface and is released in the outer layer of the bead so that in the second phase, its release is due to dissolution from the solid core. When used as an encapsulating agent, the larger the mass of agar in the beads, the denser the matrix formed and the lower the transfer of drug molecules through the beads. Similarly, the beads that contain a lower percentage of agar in the composition have a higher water content, which explains the rapid rate of drug release [131]. Therefore, agar can be used for the development of sustained-release dosage systems because it is a natural, inert, non-toxic, renewable, biocompatible, and inexpensive material.
