One-month release injectable microcapsules of a luteinizing hormone-releasing hormone agonist (leuprolide acetate) for treating experimental endometriosis in rats.
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.
D000818:Animals; D002214:Capsules; D003692:Delayed-Action Preparations; D004715:Endometriosis / Q000188:drug therapy*; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D007267:Injections; D019344:Lactic Acid; D016729:Leuprolide; D008297:Male; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains
D002214:Capsules; D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D007987:Gonadotropin-Releasing Hormone; D019344:Lactic Acid; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D016729:Leuprolide