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Biodegradable implants based on photo-cross-linked aliphatic polycarbonates for long-acting contraception

Journal of Materials Science & Technology 2023年第25期156卷 129-141页

作者： Zhipeng Hou Wei Xu Siwen Chen Jing Guo Peng Li Jianshe Hu Liqun Yang Jing Chen Center for Molecular Science and Engineering College of ScienceNortheastern UniversityShenyang 110819China NHC Key Laboratory of Reproductive Health and Medical Genetics (China Medical University) Liaoning Research Institute of Family Planning (The Reproductive Hospital of China Medical University)Shenyang 110031China Department of Biomaterials Shengjing Hospital of China Medical UniversityShenyang 110004China Department of Obstetrics and Gynecology Shengjing Hospital of China Medical UniversityShenyang 110004China

In this study,a new class of biodegradable contraceptive implants was prepared via the UV irradiation molding method,among which,progestin levonorgestrel(LNG)was used as a model drug.photo-cross-linked aliphatic polycarbonates(APCs),namely,poly(trimethylene carbonate-co-2,2′-dimethyltrimethylene carbonate)[P(TMC-co-DTC)]elastomers,were used as the drug delivery matrix.The results obtained from the degradation experiments carried out in Sprague-Dawley(SD)rats showed that the cross-linked elastomer had the degradation characteristics of the surface erosion degradation mechanism,with no generation of acid degradation products,and excellent form-stability,which met the performance requirements of the matrix for a long-acting sustained-release delivery system.The in vitro cytotoxicity tests and histological and immunohistochemical evaluations showed good biocompatibility and biosafety of the elastomer matrix material and contraceptive implants.Subsequently,the implant formulations were screened by in vitro release experiments,and their release kinetics were explored.Finally,in the evaluation study of the in vivo anti-fertility effect,the implants exhibited excellent dimensional stability and were degraded by a surface erosion mechanism.LNG achieved a stable and sustained release in female SD rats,maintaining a long-acting contraceptive duration of up to 4 months.The contraceptive implants obtained in this study could be used to address the limitations of currently available formulations,which required secondary surgical removal and a single means of regulating drug release kinetics.Therefore,these implants could provide a new option for birth control needs and may be of significance in reducing the incidence of induced abortion and protecting female fertility.

关键词： Aliphatic polycarbonates photo-cross-linked Levonorgestrel Contraceptive implants Anti-fertility effects Sustained-release

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