CONTINUOUS RELEASE OF PROTEINS FROM BIODEGRADABLE MICROCAPSULES AND IN-VIVO EVALUATION OF THEIR POTENTIAL AS A VACCINE ADJUVANT

A series of biodegradable microcapsules were prepared from blends of l actic/glycolic acid polymers for the controlled release of model prote ins such as bovine serum albumin (BSA), transferrin and trypsin. The i nfluence of microcapsule formulations on its degradability and permeab ility to proteins was demonstrated by the degree of water uptake, thei r susceptibility to hydrolysis and in vitro release characteristics of proteins. Microcapsules reported in this research provided continuous release profiles of proteins rather than polyphasic and/or pulsatile release kinetics. In vivo experiments demonstrated that continuous rel ease of a model antigen BSA evoked high-titered immune responses in mi ce which persisted for more than 142 days. The adjuvanticity of the mi crocapsules was found to be superior to that of aluminum hydroxide and comparable to that of Freund's incomplete adjuvant. Control experimen ts substantiated that the mixture of antigen and blank microcapsules d id not induce greater immune responses than BSA in saline solution alo ne, suggesting that blank microcapsules do not possess adjuvanticity a nd BSA should be encapsulated into and slowly released from microcapsu les for its immunopotentiation. In addition, immunization of animals w ith BSA-containing microcapsules was more effective in stimulating its immunogenicity than that with one prime and two booster injections of BSA in saline solution. Therefore, the microcapsule providing continu ous release of antigen can be an effective alternative to multiple inj ections of antigen and have a potential of use as vaccine adjuvants.