title: Evaluation of biodegradable microspheres containing nomegestrol acetate in a rat model of endometriosis.
abstract: We assessed the efficacy of biodegradable microspheres (MSs) containing nomegestrol acetate (NOMAC) for treatment of endometriosis in a rat model and investigated its preliminary mechanism of action. Sprague-Dawley rats with surgically implanted endometrial autografts were divided randomly into four groups of thirteen rats each, and subcutaneously injected twice (10d apart) with either empty MSs or MSs containing nomegestrol acetate (NOMAC-MS; 27-800mg per kg of rat body weight). Twenty-one days after the first injection, blood and endometriotic tissues were collected and assayed for changes in endometriotic tissue, serum hormone, liver function parameters, and apoptotic protein. No remarkable irritation was observed at the site of injection. NOMAC-MS treatment significantly reduced the volume of the endometrial autografts, decreased serum levels of estradiol, progesterone, triiodothyronine, and alanine aminotransferase, and decreased levels of estrogen receptor alpha protein. Furthermore, NOMAC-MS at the highest dose significantly reduced serum aspartate aminotransferase and endometrial antibody, reduced the Bcl-2/Bax protein ratio, and increased caspase-3 and caspase-9 proteins. There was no pronounced difference observed in alkaline phosphatase, carbohydrate antigen 125, progesterone receptor, or vascular endometrial growth factor receptor 2 (VEGFR2) in any of the tested groups relative to the control. NOMAC-MS significantly changed the expression of apoptotic protein only at the highest dose. Our findings warrant the further investigation of sustained application of steroid hormone via microspheres for the treatment of endometriosis.
authors.affiliation: Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, PR China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Reproductive Pharmacology, NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, PR China. Electronic address: zhuyan@sippr.org.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Reproductive Pharmacology, NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, PR China.
authors.forename: Xianying
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Reproductive Pharmacology, NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, PR China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Hao
authors.affiliation: Department of Reproductive Pharmacology, NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, PR China.
authors.forename: Shuwu
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Reproductive Pharmacology, NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, PR China.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Reproductive Pharmacology, NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, PR China.
authors.forename: Xiangjie
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Reproductive Pharmacology, NPFPC Key Laboratory of Contraceptives and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Pharmacy, Guangdong Medical College, Dongguan 523808, PR China.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pharmaceuticals, Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, PR China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D043384:Glutamyl Aminopeptidase / Q000378:metabolism; D008111:Liver Function Tests / Q000379:methods; D008535:Megestrol / Q000494:pharmacology*; D008863:Microspheres; D009649:Norpregnadienes / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D009649:Norpregnadienes; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D014284:Triiodothyronine; D011374:Progesterone; D004958:Estradiol; C038501:nomegestrol acetate; D008535:Megestrol; D000410:Alanine Transaminase; D043384:Glutamyl Aminopeptidase; D053148:Caspase 3; D053453:Caspase 9
keywords: Bax; Bcl-2; Biodegradable microsphere; Caspase; Endometriosis; Nomegestrol acetate