Formulation, characterization and optimization of Hepatitis B surface antigen (HBsAg)-loaded chitosan microspheres for oral delivery

Abstract

Context: Approximately 400 million persons worldwide have chronic hepatitis B. This is due to problems associated with vaccine delivery, stability and cost. Hence the present challenge in vaccinology is to develop safer, cheaper and easy-to-deliver forms of vaccines. A novel needle-free oral vaccine will be an ideal tool to fight this silent killer disease.Objective: The aim of this work was to prepare and evaluate chitosan-loaded HBsAg microspheres for oral delivery.Materials and methods: Chitosan microspheres were prepared by emulsion solvent evaporation technique. To overcome the enzymatic and permeation barrier, protease inhibitors and permeation enhancers were also added. Studies were conducted to find the effect of stabilizer concentration, stirring speed, cross-linking agent and polymer concentration on microsphere size and entrapment efficiency. Formulations were characterized for their particle size, entrapment efficiency. They were also evaluated for the in vitro drug release, in vivo performances and the effect of different storage conditions.Results: HBsAg-loaded chitosan microspheres with bacitracin as protease inhibitor showed better protective levels of immunity after oral administration comparing with aprotinin as protease inhibitor. Stability at room temperature up to a period of four months reduces incomplete vaccine coverage and logistic requirements.Conclusion: The study signifies the potential of the formulated chitosan microspheres for effective oral administration of HBsAg.