Formulation and characterization of Chitosan coated PLA/PLGA encapsulated microparticles for vaccine development

Abstract

Thermoplastic aliphatic poly(esters) like poly(lactide) (PLA), poly(glycolide) (PGA), and especially the copolymer of lactide and glycolide, poly(lactide-co-glycolide) (PLGA) microparticles (MP) have generated immense interest due to their favorable properties such as good biocompatibility, biodegradability, and represent a promising and efficient delivery system for mucosal vaccination. The surface modification of these polymers and coating with polycationic polymers like chitosan can produce new formulations with unique properties. Chitosan coatings exhibit an important fraction of primary amino groups to the environment; these amino groups are freely accessible for a variety of mild coupling reactions for bioactive ligands. The positive charge of chitosan coating likely promotes the ionic binding of nucleic acids, either for gene vaccination purposes, e.g., plasmid DNA or mRNA or to deliver an immunoadjuvant to single-stranded RNA like in case of delivery of encapsulated rotavirus (RV). RV is one of the major causes of infantile gastroenteritis diarrhea. It is responsible for more than 150,000 deaths under the age of five in India every year. This emphasizes an urgent need for a vaccine to control such a large number of childhood mortality. Chitosan was used both as blend and coating to PLA and PLGA microparticle. The PLA-Chi, PLGA-Chi microparticles were prepared by solvent extraction evaporation method using a recently developed microextrusion-based technique along with the addition of various stabilizers. Along with the RV antigen, emulsifier mice serum albumin 2.5% W/V, lyoprotectant sucrose (10%, W/V) and 2% W/V Sodium bicarbonate were added to internal aqueous phases to stabilize the antigen. The particles were characterized with particle size determination, Zeta potential, while SEM and TEM studies along with their in vitro release studies are under progress. The details of the result obtained will be discussed during the presentation.