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In vitro and in vivo analysis of antide delivery from multi‐phase microspheres fabricated via solvent removal
Author(s) -
Branton Jennifer F.Godbee,
Cheifetz Peter M.,
Scott Evan A.,
Bubbers Emily J.,
Mathiowitz Edith
Publication year - 2005
Publication title -
israel journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.908
H-Index - 54
eISSN - 1869-5868
pISSN - 0021-2148
DOI - 10.1560/82r2-fkdn-hw6g-r5ky
Subject(s) - in vivo , chemistry , testosterone (patch) , castration , in vitro , hormone , pharmacology , endocrinology , biochemistry , medicine , microbiology and biotechnology , biology
Antide, a gonadotropin releasing hormone (GnRH) antagonist, has been studied as a new drug for treatment of various gonadotropin‐dependent disorders, including hormone‐dependent prostate and breast cancer. Antide was encapsulated into multi‐phase microspheres composed of poly(l‐lactic)acid (PLLA) and poly(fumaric‐co‐sebacic)anhydride (P(FA:SA)) fabricated via solvent removal and loaded at 5% and 20% (w/w). In vitro release kinetics and the in vivo therapeutic effect (changes in the testosterone levels) were evaluated. In vivo studies were conducted in male rats at a dose of 12.5 mg antide/kg for both the 5% and 20% loaded particles as well as 31.5 mg antide/kg for the 20% loaded particles. The 5% loaded particles achieved a decrease in testosterone levels below the castration level (0.5 ng/mL) over the course of 11 weeks. The 20% loaded particles resulted in testosterone levels below the castration level for 7 weeks. The results of these studies demonstrate that it is possible to encapsulate antide into a controlled delivery system for more than 2 months. Furthermore, we were able to achieve a therapeutic response in vivo indicated by serum testosterone levels below the castration level of 0.5 ng/mL for at least 11 weeks.