Novel application of trimethyl chitosan as an adjuvant in vaccine delivery

The application of natural carbohydrate polysaccharides for antigen delivery and its adjuvanation potential has garnered interest in the scientific community in the recent years. These biomaterials are considered favorable candidates for adjuvant development due to their desirable properties like enormous bioavailability, non-toxicity, biodegradability, stability, affordability, and immunostimulating ability. Chitosan is the one such extensively studied natural polymer which has been appreciated for its excellent applications in pharmaceuticals. Trimethyl chitosan (TMC), a derivative of chitosan, possesses these properties. In addition it has the properties of high aqueous solubility, high charge density, mucoadhesive, permeation enhancing (ability to cross tight junction), and stability over a range of ionic conditions which makes the spectrum of its applicability much broader. It has also been seen to perform analogously to alum, complete Freund's adjuvant, incomplete Freund's adjuvant, and cyclic guanosine monophosphate adjuvanation, which justifies its role as a potent adjuvant. Although many review articles detailing the applications of chitosan in vaccine delivery are available, a comprehensive review of the applications of TMC as an adjuvant is not available to date. This article provides a comprehensive overview of structural and chemical properties of TMC which affect its adjuvant characteristics; the efficacy of various delivery routes for TMC antigen combination; and the recent advances in the elucidation of its mechanism of action.