Size effect on the antibody production induced by biodegradable microspheres containing antigen

Poly(L-lactic acid) (PLLA) microspheres containing a model antigen, ovalbumin (OVA), were prepared by the evaporation method using double emulsion, and fractionated into different sizes by counterflow elutriation. Following the intraperitoneal (i.p.) and subcutaneous (s.c.) injection of the microspheres to mice, the titer of anti-OVA antibody in the serum was measured to assess the size effect on the profile of antibody production. OVA was released from the microspheres for 80 days, irrespective of the microsphere size. In both the s.c. and i.p. immunization, the serum level of anti-OVA IgG antibody in the mice induced by the microspheres containing OVA was higher than that of free OVA when compared at the same dose. The serum level of antibody in the mice i.p. injected with the microspheres tended to increase with the decreasing size. On the other hand, in the s.c. immunization, the microsphere size had little influence on the antibody production. It is possible that the injected microspheres tend to aggregate in the s.c. tissue, disappearing the size effect on the antibody production. Since the amount of microspheres injected increases with the decreasing size when their OVA loading is fixed, the increase in the amount will promote the interaction with immune cells, resulting in an enhanced antibody production. The cell interaction with the microspheres in the peritoneal cavity seems to be influenced by their size to a greater extent than in the s.c. tissue, probably because of their more frequent interaction with immune cells.