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 lactic/glycolic acid polymers for the controlled release of model proteins such as bovine serum albumin (BSA), transferrin and trypsin. The influence of microcapsule formulations on its degradability and permeability to proteins was demonstrated by the degree of water uptake, their 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 release of a model antigen BSA evoked high-titered immune responses in mice which persisted for more than 142 days. The adjuvanticity of the microcapsules was found to be superior to that of aluminum hydroxide and comparable to that of Freund's incomplete adjuvant. Control experiments substantiated that the mixture of antigen and blank microcapsules did not induce greater immune responses than BSA in saline solution alone, suggesting that blank microcapsules do not possess adjuvanticity and BSA should be encapsulated into and slowly released from microcapsules for its immunopotentiation. In addition, immunization of animals with 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 continuous release of antigen can be an effective alternative to multiple injections of antigen and have a potential of use as vaccine adjuvants.