Characterization of polymeric poly(ϵ‐caprolactone) injectable implant delivery system for the controlled delivery of contraceptive steroids

Characterization of polymeric poly(ϵ‐caprolactone) injectable implant delivery system for the controlled delivery of contraceptive steroids Magharla Dasaratha Dhanaraju Damodaran Gopinath Mohamed Rafiuddin Ahmed Rajadas Jayakumar Chandrasekar Vamsadhara Abstract

Contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) have been encapsulated with poly(ϵ‐caprolactone) (PCL) microspheres using a w/o/w double emulsion method. The microspheres prepared were smooth and spherical, with a mean size from 8–25 μm. In vitro release profiles of microspheres showed a trend of increasing initially at the first week, and thereafter the release was sustained. At the end of the seventh week LNG/EE from 1:5 and 1:10 PCL microspheres were 60 and 48%, 52 and 46%, respectively. An in vitro degradation study shows that at the 20th week the microspheres maintained the surface integrity. The PCL microspheres showed a triphasic in vivo release profile with an initial burst effect due to the release of the steroid adsorbed on the microsphere surface, a second sustained release phase due to the steroid diffusion through the pores or channels formed in the polymer matrix, and third phase due to polymer bioerodible. Histological examination of PCL microspheres injected intramuscularly into thigh muscle of a rat showed a minimal inflammatory reaction demonstrating that contraceptive steroid‐loaded microspheres were biocompatible. The level of inflammatory cytokines determined by immunostaining for IL‐1α, the tissue response to formulations at the first week was considered mild, whereas at the end of the 20th week the inflammatory response ceased. Thus, this study helped us to evaluate the feasibility of using these microspheres as a long‐acting biodegradable drug delivery system for contraceptive steroids. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006
08 17 2005 01 2006 63 72 10.1002/jbm.a.30458 http://onlinelibrary.wiley.com/termsAndConditions#vor 10.1002/jbm.a.30458 https://onlinelibrary.wiley.com/doi/10.1002/jbm.a.30458 https://onlinelibrary.wiley.com/doi/pdf/10.1002/jbm.a.30458 http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjbm.a.30458 10.1016/0168-3659(94)00107-6 10.1016/S0169-409X(97)00125-7 10.1016/S0169-409X(97)00124-5 Biomedical applications of polymeric materials Ishihara K 89 1993 10.1002/(SICI)1097-4636(20000605)50:3<388::AID-JBM13>3.0.CO;2-F 10.1016/S0142-9612(99)00276-8 Biomaterials Athanaasiou KA 93 17 1996 Sterilization, toxicity, biocompatibility and clinical applications of poly(L‐lactide) for use as internal fixation of fractures: A study in rats Proc Int Symp Controlled Release Bioact Mater Lim LY 111 15 1998 The influence of environmental conditions on damage in L‐poly‐lactic acid during gamma irradiation 10.1016/0168-3659(94)00100-9 Biodegradable polymers as drug delivery systems Pitt CG 71 1990 10.1016/0378-5173(91)90108-Z 10.3109/03639049809082719 Biodegradable polymers as drug delivery systems Pitt CG 71 1990 10.1023/A:1018912426983 10.1056/NEJM199607043350102 10.1023/A:1016419303727 10.1111/j.2042-7158.1995.tb05760.x Cancer Res Verrijk R 6653 52 1992 Reduction of systemic exposure and toxicity of cisplatin by encapsulation in poly(lactide‐co‐glycolide) 10.3109/02652049309015322 10.1016/S0076-6879(85)12010-0 World Meet Pharm Biopharm Pharm Technol Giunchedi P 389 1 1995 PDLLA microspheres containing steroids: Spray‐drying and w/o/w emulsification as preparation methods 10.1016/S0168-3659(97)00113-2 10.1016/0002-9378(81)90743-2 Proc Int Symp Controlled Release Bioact Mater O'Hern PA 394 20 1993 Development of a contraceptive peptide vaccine for use with PGAL microspheres 10.1248/cpb.52.976 10.1016/j.ijpharm.2003.08.011 10.1039/a604558h J Pharm Sci Technol Lu W 13 49 1995 Protein release from poly(lactic‐co‐glycolic acid) microspheres: Protein stability problems 10.1016/S0141-3910(99)00145-7 10.1016/S0168-3659(97)00096-5 10.1016/1054-8807(93)90045-4 10.1097/00002480-198804000-00005 10.1016/0142-9612(88)90063-4 10.1016/S0022-2143(97)90072-X Cytokines in health and disease Wewers MD 235 1992 Eur J Pharm Biopharm Anderson JM 1 40 1994 In vivo biocompatibility of implantation delivery systems and biomaterials Prob Gen Surg Anderson JM 147 11 1994 Inflammation and the foreign body response 10.1084/jem.141.6.1278