One-month release injectable microcapsules of a luteinizing hormone-releasing hormone agonist (leuprolide acetate) for treating experimental endometriosis in rats.

Abstract

Leuprolide acetate is a highly potent analog of luteinizing hormone-releasing hormone. We have prepared 1-month release injectable microcapsules of leuprolide acetate using a biodegradable polymer, poly (dl-lactide-co-glycolide), to treat an endocrine-dependent tumor, prostate cancer. In the present study, the possibility using the microcapsules to treat endometriosis was investigated. In rats, the microcapsules exhibited a pseudo-zero order release from the injection site for 1 month after being administered s.c. and i.m., and maintained effective constant serum levels of the analog during the 4-week treatment. A single injection of the microcapsules (100 micrograms/kg/day as leuprolide acetate) suppressed luteinizing hormone, follicle-stimulating hormone and estradiol for more than 4 weeks, and caused a dramatic regression of growth of Jones experimental endometriosis model in female rats. These results encourage the belief that a 1-month release parenteral preparation of leuprolide acetate may be potentially useful in the therapy of endometriosis in human beings.