Drug delivery using biodegradable microspheres

Abstract

Rational delivery systems for leuprorelin acetate, a potent LHRH agonist, have been achieved by developing a microsphere system using biodegradable polymers, poly(lactic/glycolic acid) (PLGA) and polylactic acid, which sustainedly release the drug depending on the biodegradation of polymer used and persistently suppress steroidogenesis for over one and 3 months, respectively, following a single injection. To produce these systems we established a novel microencapsulation technique, the in-water drying method, and microspheres with a high trap ratio and small initial burst were obtained. A microsphere system of TRH prepared using PLGA could also continuously release the drug for 2 or 4 weeks. Using these systems effectively reduced the required dose compared with that needed with daily injection due to more continuous receptor hits on the target organs and could improve patient compliance. Chemoembolization using PLGA microspheres containing an angiogenesis inhibitor, TNP-470, resulted in dramatic regression of VX-2 carcinoma in rabbits. The microsphere system using biod-egradable polymers is very useful in designing controlled release delivery and targeted delivery to attain potent and rational therapy.