Evaluation of Biodegredable Microparticles for Mucosal Vaccination Against Diphtheria Toxoid: Nasal Efficacy Studies in Guinea Pigs

Abstract

Introduction: In this study, Poly-(ɛ-caprolactone) (PCL) and Poly-(lactic-co-glycolic acid) (PLGA) microparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. Materials and Methods: The antigen-containing microparticles were prepared using double emulsion (w/o/w) solvent evaporation method. Results: The average geometric diameter of the particles were found between 7 and 24 µm which is suitable for uptake by the antigen presenting cells in the nasal mucosa. Although the differences were not significant, PLGA polymer containing formulations exhibited the highest encapsulation efficiency. The microparticle formulations, prepared with both PLGA and PCL polymers, was successfully produced at high production yields. The in vitro release profile was presented as a biexponential process with an initial burst effect due to the release of the protein adsorbed on the microsphere surface and the subsequent sustained release profile is the result of protein diffusion through the channels or pores formed in the polymer matrix. DT loaded microparticles, DT solution in phosphate buffered saline and empty microparticles (as control) were administered via nasal route and subcutaneously to guinea pigs. The antibody content of each serum sample was determined by an enzyme-linked immunosorbent assay. Conclusion: Absorbance values of ELISA test showed that PLGA and PCL bearing microparticles were able to stimulate adequate systemic immune response with intranasal vaccination. Additionally, PLGA and PCL microparticles resulted in significantly increased IgG titers with intranasal administration as a booster dose following subcutaneous administration. PCL polymer elicited a high immune response compared to PLGA polymer (p<0,05).