PHARMACOKINETIC STUDY OF ~(14)C-VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) MICROSPHERES IN RATS

摘要

Poly(lactic-co-glycolic) acid microspheres are utilized to alter the pharmacokinetics of Vascular Endothelial Growth Factor (VEGF) following s.c. administration. The PK parameters of VEGF in PLGA microspheres were compared with those of ~(14)C-VEGF solutions, using a rat model. The s.c. administration of protein solutions resulted in high plasma and low s.c. concentrations, suggesting rapid absorption and elimination. Whereas, s.c. administration of the microsphere formulations resulted in low plasma and high s.c. site concentrations, suggesting that the absorption phase is controlled by release rate from the microspheres. The in vitro and in vivo release and microsphere degradation rates followed the same rank order and confirmed that drug release was diffusion controlled.