By: Su Hyun Kim
According to the Centers for Disease Control and Prevention, cancer is the second leading cause of death in America. One important criteria for a successful cancer treatment is targeted therapy to tumor sites. Polymers with the ability to carry the drug or antigen to the site of action while being biodegradable, immunogenic, as well as having controlled release capabilities are valuable candidates for delivery systems. Alginates are especially noteworthy as a potential antigen carrier for having all the prior mentioned attributes, and for having mucoadhesive properties for increasing residence time via different routes of administration.
Alginates are anionic polysaccharides extracted from brown seaweed and consist of two monomers: mannuronic acid and guluronic acid. This sugar can be water-soluble or insoluble. Sodium alginate is water-soluble, whereas additions of divalent cations like Ca2+ result in an insoluble hydrogel that acts as a film-former. Using this unique physical property, many formulations use aqueous solutions of sodium alginate to mix in proteins and then add calcium chloride to produce an extended release product containing encapsulated protein.
Alginates are also used as a delivery adjuvant to enhance immunogenicity of antigens within it. R.R. Jain et al. demonstrate how alginate microencapsulation improves immunogenicity of antigens and promotes antibody responses to the antigen more effectively than free soluble antigens. R. Aquino et al. explain how alginates are capable of inducing cytokine production from monocytes—by interacting with its mannuronic acid residues. Hence, alginates are an attractive delivery platform for scientists who wish to amplify immune response towards antigens.
Alginates also show mucoadhesive properties, thus extending contact time of microparticles to mucosal surfaces found in numerous regions in the body. This makes it a valuable candidate for encapsulation of drugs or biologics to be administered via noninvasive routes of administration. Alginate microparticles can adhere to intestinal mucosa to increase the systemic absorption time of the drug, enabling oral delivery of antigens to be a viable option. Alginate microparticles adhere to absorptive epithelium and mucosa associated lymphoid tissue in trachea effectively releasing antigens to induce a significant immune response, which allow pulmonary administration of drug as well. Mucoadhesive properties also lead to minimization of drug metabolism allowing the drug to achieve its maximum efficiency.
Alginates can control the release kinetic of drugs with their pH-dependent swelling capacity. Alginates do not swell in stomach acid, thus protecting pH-sensitive proteins inside its microparticles. However, they do swell at higher pH found in intestinal fluid to release drugs for absorption while achieving its maximum swelling at pH 7.2. Hydrogel in contact with biofluid absorbs water to loosen the matrix, allowing inner microparticles to diffuse out of its system.
Alginates have been receiving more attention than ever in the past 5 years. Every year, new studies are being posted in journals to prove their superior advantages as a biopolymer carrier over other carriers. Besides being cheap and biodegradable, alginates are immunogenic, mucoadhesive and capable of swelling to facilitate extended release, promising an innovative method for targeted drug delivery in cancer treatment. Currently, I am working on the delivery of antigen with adjuvants within alginate carrier with Gary Bumgarner, Ph.D. and Bernadette D’Souza, Ph.D., and excitingly, it has succeeded to be an ideal carrier in-vitro experiments—alginates are the antigen carriers of the future.