{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:39:07Z","timestamp":1791297547795,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,8,17]],"date-time":"2005-08-17T00:00:00Z","timestamp":1124236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) have been encapsulated with poly(\u03f5\u2010caprolactone) (PCL) microspheres using a w\/o\/w double emulsion method. The microspheres prepared were smooth and spherical, with a mean size from 8\u201325 \u03bcm. <jats:italic>In vitro<\/jats:italic> 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 <jats:italic>in vitro<\/jats:italic> degradation study shows that at the 20th week the microspheres maintained the surface integrity. The PCL microspheres showed a triphasic <jats:italic>in vivo<\/jats:italic> 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\u2010loaded microspheres were biocompatible. The level of inflammatory cytokines determined by immunostaining for IL\u20101\u03b1, 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\u2010acting biodegradable drug delivery system for contraceptive steroids. \u00a9 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2006<\/jats:p>","DOI":"10.1002\/jbm.a.30458","type":"journal-article","created":{"date-parts":[[2005,8,17]],"date-time":"2005-08-17T19:47:52Z","timestamp":1124308072000},"page":"63-72","source":"Crossref","is-referenced-by-count":59,"title":["Characterization of polymeric poly(\u03f5\u2010caprolactone) injectable implant delivery system for the controlled delivery of contraceptive steroids"],"prefix":"10.1002","volume":"76A","author":[{"given":"Magharla","family":"Dasaratha Dhanaraju","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damodaran","family":"Gopinath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Rafiuddin Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajadas","family":"Jayakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrasekar","family":"Vamsadhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,8,17]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-3659(94)00107-6"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00125-7"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00124-5"},{"key":"e_1_2_7_5_2","first-page":"89","volume-title":"Biomedical applications of polymeric materials","author":"Ishihara K","year":"1993"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(20000605)50:3<388::AID-JBM13>3.0.CO;2-F"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(99)00276-8"},{"key":"e_1_2_7_8_2","first-page":"93","article-title":"Sterilization, toxicity, biocompatibility and clinical applications of poly(L\u2010lactide) for use as internal fixation of fractures: A study in rats","volume":"17","author":"Athanaasiou KA","year":"1996","journal-title":"Biomaterials"},{"key":"e_1_2_7_9_2","first-page":"111","article-title":"The influence of environmental conditions on damage in L\u2010poly\u2010lactic acid during gamma irradiation","volume":"15","author":"Lim LY","year":"1998","journal-title":"Proc Int Symp Controlled Release Bioact Mater"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-3659(94)00100-9"},{"key":"e_1_2_7_11_2","first-page":"71","volume-title":"Biodegradable polymers as drug delivery systems","author":"Pitt CG","year":"1990"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5173(91)90108-Z"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.3109\/03639049809082719"},{"key":"e_1_2_7_14_2","first-page":"71","volume-title":"Biodegradable polymers as drug delivery systems","author":"Pitt CG","year":"1990"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018912426983"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199607043350102"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1016419303727"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1995.tb05760.x"},{"key":"e_1_2_7_19_2","first-page":"6653","article-title":"Reduction of systemic exposure and toxicity of cisplatin by encapsulation in poly(lactide\u2010co\u2010glycolide)","volume":"52","author":"Verrijk R","year":"1992","journal-title":"Cancer Res"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.3109\/02652049309015322"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(85)12010-0"},{"key":"e_1_2_7_22_2","first-page":"389","article-title":"PDLLA microspheres containing steroids: Spray\u2010drying and w\/o\/w emulsification as preparation methods","volume":"1","author":"Giunchedi P","year":"1995","journal-title":"World Meet Pharm Biopharm Pharm Technol"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(97)00113-2"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(81)90743-2"},{"key":"e_1_2_7_25_2","first-page":"394","article-title":"Development of a contraceptive peptide vaccine for use with PGAL microspheres","volume":"20","author":"O'Hern PA","year":"1993","journal-title":"Proc Int Symp Controlled Release Bioact Mater"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.52.976"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2003.08.011"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1039\/a604558h"},{"key":"e_1_2_7_29_2","first-page":"13","article-title":"Protein release from poly(lactic\u2010co\u2010glycolic acid) microspheres: Protein stability problems","volume":"49","author":"Lu W","year":"1995","journal-title":"J Pharm Sci Technol"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0141-3910(99)00145-7"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(97)00096-5"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/1054-8807(93)90045-4"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002480-198804000-00005"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(88)90063-4"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2143(97)90072-X"},{"key":"e_1_2_7_36_2","first-page":"235","volume-title":"Cytokines in health and disease","author":"Wewers MD","year":"1992"},{"key":"e_1_2_7_37_2","first-page":"1","article-title":"In vivo biocompatibility of implantation delivery systems and biomaterials","volume":"40","author":"Anderson JM","year":"1994","journal-title":"Eur J Pharm Biopharm"},{"key":"e_1_2_7_38_2","first-page":"147","article-title":"Inflammation and the foreign body response","volume":"11","author":"Anderson JM","year":"1994","journal-title":"Prob Gen Surg"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.141.6.1278"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbm.a.30458","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.30458","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T19:29:14Z","timestamp":1696879754000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.30458"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,8,17]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["10.1002\/jbm.a.30458"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.30458","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,8,17]]}}}