Immune response to nasal delivery of antigenically intact tetanus toxoid associated with poly(L-lactic acid) microspheres in rats, rabbits and guinea-pigs.

Tetanus toxoid was adsorbed onto poly(L-lactic acid) microspheres. Analyses by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting suggest that the formulation procedure does not affect the stability or the antigenic properties of the protein. After nasal administration to guinea-pigs, the resulting preparation enhanced the immune response to the tetanus toxoid when compared with the free antigen. The increase in systemic immunoglobulin G titre was almost immediate in the group treated with the adsorbed tetanus toxoid (time zero, 140; week 2, 1550; week 4, 2760), reaching 36,000 two weeks after the booster (week 7), whereas the free antigen produced an immune response similar to that found in non-treated animals. In a parallel experiment, latex particles of a similar size to poly(L-lactic acid) microspheres, administered to both rats and rabbits, were detected in the blood stream. These findings with tetanus toxoid demonstrate the use of microsphere delivery systems for nasal application of antigens. These had a profound effect on the immune response, and indicate possibilities for overcoming some of the barriers to drug absorption in general.