Preparation Of Novel Oral Vaccines Carrier By Combining Morphology Control And Coating Modification

Oral vaccines have attracted much attention due to their advantages of high patient compliance,convenient vaccination,reduction in the production of related harmful waste,and mucosal immunity.However,there are very few types of oral vaccines currently on the market,mainly due to the defects of low bioavailability of oral vaccines.The strong acidic environment of the stomach and the degradation of protease,the p H change from acid to alkali in the intestine,the obstruction of the intestinal mucus layer,and the slow absorption of the small intestinal epithelium restrict the immune effect of oral vaccines.Therefore,how to overcome the above-mentioned obstacles in the oral delivery process and improve the immune effect of oral vaccines is an urgent problem to be solved in the development of oral vaccines.In view of the above problems,this research proposes to control the morphology of Polylactic acid-glycolic acid copolymer(PLGA)particles to prepare PLGA rod-shaped particles that can be absorbed by the small intestinal epithelium faster.Preparation of Oral Vaccine Carriers by Plating Modification of PLGA Rod-shaped Particles withβ-Glucan and Thiolated Hydroxypropyl Methylcellulose Phthalate(T-HPMCP)with intestinal targeted release properties.The results show that the oral vaccine carrier can be absorbed by the intestinal epithelium more quickly and can promote the activation of dendritic cells(DC cells),and can also significantly increase the antibody titer level of humoral and mucosal immunity,and promote T cells activation and generation of memory T cells.The specific research contents are as follows:(1)The PLGA rod-shaped particles were prepared by combining the solvent evaporation method and the rapid membrane emulsification method,and the factors affecting the deformation of the PLGA particles were explored,that is,the influence of the concentration of PBS,the concentration of PVA and the stirring speed on the deformation of the particles.And determine the best formula to prepare PLGA rod-shaped particles with a length of 2-4μm and a width of 1-2μm suitable for intestinal epithelial cell uptake.At the same time,T-HPMCP was synthesized according to the literature,and the PLGA rod-shaped particles were modified by plating usingβ-glucan and T-HPMCP.The coating potential and p H sensitivity in vitro and in vivo were characterized,demonstrating the presence of each coating and its ability to maintain antigenic activity in an acidic environment.(2)Investigating the effect of plated PLGA rod-shaped particles at the cellular level:evaluating the uptake and transport efficiency of PLGA rod-shaped particles by intestinal epithelial cells,the toxicity to intestinal epithelial cells,and the activation effect on DC cells.The results show that rod-shaped particles can be taken up and transported faster than spherical particles,and they are non-toxic.The PLGA rod-shaped particles coated withβ-glucan can significantly activate DC cells.(3)Investigate the effect of the coated PLGA rod-shaped particles at the animal level:verify the ability of the coated PLGA rod-shaped particles to deliver to the ileum,the effect of different coated PLGA particles on humoral and mucosal immunity,the effect of different coated PLGA particles on cellular immunity,and biosafety of coated PLGA rod-particles.The results demonstrate the ability of T-β-glucan PLGA rod-shaped particles to be targeted for delivery to the ileal site,and the T-β-glucan PLGA rod-shaped particles significantly increased the Ig G and Ig A antibody titers of oral immunization,and also Improve the specific killing effect of CD8~+T cells and the generation of memory T cells,and the coated PLGA rod-shaped particles have good biocompatibility.In summary,the prepared coating-modified PLGA rod-shaped particles as oral vaccine carriers can overcome multiple barriers in the oral delivery process and significantly improve the immune effect,and provides new materials and ideas for the study of oral vaccines,as well as references for subsequent studies on oral vaccines and oral drug delivery materials.