Guilei Ma1, Cunxian Song, Hongfan Sun, Jing Yang, Xigang Leng. 1. The Tianjin Key Laboratory of Biomaterials, Institute of Biomedical Engineering, Peking Union Medical College and Chinese Academy of Medical Sciences, Nankai District, Tianjin 300192, China.
Abstract
PURPOSE: Our objective was to report preclinical studies on a biodegradable long-acting contraceptive implant. METHODS: A poly (epsilon-caprolactone) (PCL)/pluronic F68 (F68) compound was used to construct an implant, which was filled with dry levonorgestrel (LNG) powder (PCL/F68/LNG). LNG release rate, contraceptive efficacy and polymer degradation were evaluated in rats and followed for 2 years. A 2-year toxicity study was conducted in dogs. RESULTS: The in vitro and in vivo release of LNG from the implant followed zero-order release kinetics. Serum LNG level in rats was very stable during the 2-year period. Studies on polymer degradation indicated that the molecular weight of PCL dropped from 66,000 to 15,000 Da, but the implant was still in good shape by the end of 2 years. CONCLUSION: Toxicological study demonstrated that the PCL/F68 polymer had no adverse effect in all aspects. The contraceptive efficacy in rats showed dose response. The implant was physically and chemically stable for up to 3 years in airproof aluminum foil packing at room temperature.
PURPOSE: Our objective was to report preclinical studies on a biodegradable long-acting contraceptive implant. METHODS: A poly (epsilon-caprolactone) (PCL)/pluronic F68 (F68) compound was used to construct an implant, which was filled with dry levonorgestrel (LNG) powder (PCL/F68/LNG). LNG release rate, contraceptive efficacy and polymer degradation were evaluated in rats and followed for 2 years. A 2-year toxicity study was conducted in dogs. RESULTS: The in vitro and in vivo release of LNG from the implant followed zero-order release kinetics. Serum LNG level in rats was very stable during the 2-year period. Studies on polymer degradation indicated that the molecular weight of PCL dropped from 66,000 to 15,000 Da, but the implant was still in good shape by the end of 2 years. CONCLUSION: Toxicological study demonstrated that the PCL/F68 polymer had no adverse effect in all aspects. The contraceptive efficacy in rats showed dose response. The implant was physically and chemically stable for up to 3 years in airproof aluminum foil packing at room temperature.
Authors: William R Lykins; Ellen Luecke; Daniel Johengen; Ariane van der Straten; Tejal A Desai Journal: Drug Deliv Transl Res Date: 2017-12 Impact factor: 4.617