Rational delivery systems for leuprorelin acetate, a potent LHRH agoni
st, have been achieved by developing a microsphere system using biodeg
radable polymers, poly(lactic/glycolic acid) (PLGA) and polylactic aci
d, 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 s
mall initial burst were obtained. A microsphere: system of TRH prepare
d using PLGA could also continuously release the drug for 2 or 4 weeks
. Using these systems effectively reduced the required dose compared w
ith that needed with daily injection due to more continuous receptor h
its on the target organs and could improve patient compliance. Chemoem
bolization using PLGA microspheres containing an angiogenesis inhibito
r, TNP-470, resulted in dramatic regression of VX-2 carcinoma in rabbi
ts. The microsphere system using biodegradable polymers is very useful
in designing controlled release delivery and targeted delivery to att
ain potent and rational therapy.