A sustained release
poly(DL-lactide-co-glycolide) (PLGA)
microsphere delivery system to treat
prostate cancer for a
luteinizing hormone-releasing hormone (
LHRH) antagonists,
LXT-101 was prepared and evaluated in the paper.
LXT-101 microspheres were prepared from PLGA by three methods: (1) double-
emulsion solvent extraction/evaporation technique, (2) single-
emulsion solvent extraction/evaporation technique, and (3) S/O/O (solid-in-oil-in-oil) method. The
microspheres were investigated on
drug loading, particle size, surface morphology and in vitro release profiles. An accelerated release approach was also established in order to expedite the evaluation periods. The in vivo evaluation of the
microspheres was made by monitoring
testosterone levels after subcutaneous administration to rats. The
LXT-101 PLGA
microspheres showed smooth and round surfaces according to a scanning electron microscopic investigation, and average particle size of ca. 30 mum according to
laser diffractometry. The
drug encapsulation efficiency of
microspheres was influenced by LA/GA ratio of PLGA,
salt concentrations,
solvent mixture and preparation methods. Moreover, LA/GA ratio of PLGA, different preparation methods and different
peptide stabilizers affected in vitro release of drugs. In vivo study, the
testosterone levels were suppressed to
castration up to 42 d as for the 7.5 mg/kg dose. And in vivo performance of
LXT-101 microspheres was dose-dependent. The weights of rat sexual organs decreased and histopathological appearance of testes had little changes after 4-month
microspheres therapy. This also testified that
LXT-101 sustained release
microspheres could exert the efficacy to suppress the
testosterone level to
castration with little toxicity. In conclusion, the PLGA
microspheres could be a well sustained release system for
LXT-101.