Biodegradable microparticles with different release profiles: Effect on the immune response after a single administration via intranasal and intramuscular routes

In the development of single-dose microparticulate vaccines, identification of the type of protein release profile required to elicit high and sustain able immune responses is important. Microparticles exhibiting different pro tein release profiles (continuous, pulsatile and plateau) were made by solv ent evaporation or solvent extraction methods from biodegradable polymers e ncapsulating the model antigen, bovine serum albumin (BSA). The immune resp onses obtained after a single intranasal or intramuscular administration of microparticles were determined, and also after a subcutaneous boost after 11 months. Microparticles were manufactured with acceptable protein loading and averag e volume size ranging from 1 to 10 mum. The integrity of BSA extracted and released from microparticles after 2 months incubation was retained. Microp articulate preparations administered by either intranasal or intramuscular routes, evoked rapid, high titre and long-lived (up to 11 months after prim ing) specific serum IgG responses which were significantly greater than for free BSA. The type of protein release from microparticles had no significa nt effect on the systemic immune responses. Interestingly, a formulation ex hibiting a plateau-release profile was the only microparticulate system cap able of inducing significantly greater IgA responses than free BSA after in tranasal immunization. This study shows the benefit of microencapsulation in inducing high and lon g-lasting systemic immune responses after a single dose by both parenteral and mucosal delivery. We conclude that of the microparticles tested, the lo ngevity and magnitude of humoral responses was not effected by the type of in-vitro protein release profile.