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Zero-Order Release of Gossypol Improves Its Antifertility Effect and Reduces Its Side Effects Simultaneously
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-01-22 00:00:00 , DOI: 10.1021/acs.biomac.7b01648 Na Wen 1, 2 , Yansheng Dong 1 , Rui Song 1 , Wenpeng Zhang 1 , Chao Sun 1 , Xiaomei Zhuang 1 , Ying Guan 2 , Qingbin Meng 1 , Yongjun Zhang 2
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-01-22 00:00:00 , DOI: 10.1021/acs.biomac.7b01648 Na Wen 1, 2 , Yansheng Dong 1 , Rui Song 1 , Wenpeng Zhang 1 , Chao Sun 1 , Xiaomei Zhuang 1 , Ying Guan 2 , Qingbin Meng 1 , Yongjun Zhang 2
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Gossypol was considered a promising male contraceptive but finally failed due to two side effects: hypokalemia and the irreversibility of its contraceptive effect. Here we demonstrate that sustained zero-order release could be a solution for these problems. The in vitro release of gossypol from gossypol/PEG layer-by-layer films follows a perfect zero-order kinetics. In vivo tests indicate that the films can maintain the plasma drug concentration constant in male SD rats for ∼20 days for a 30-bilayer film. The plasma drug concentration is 2 orders of magnitude lower than the peak plasma drug concentration when administered orally and the daily dose is >50-fold lower than the commonly used contraceptive oral dose. However, significant antifertility effects were still observed. Furthermore, hypokalemia was not observed, and the antifertility effects can be reversed after a recovery period. The results suggest that zero-order release can significantly improve the desired antifertility effect of gossypol and, meanwhile, significantly reduce its side effects. We envision the drug could be developed to be an effective, safe, and reversible male contraceptive by zero-order release.
中文翻译：
棉酚的零级释放同时改善了其抗生育作用并减少了其副作用
棉酚被认为是一种有前途的男性避孕药，但由于以下两个副作用而最终失败：低血钾症及其避孕作用的不可逆性。在这里，我们证明持续的零级释放可以解决这些问题。从棉酚/ PEG逐层薄膜中释放棉酚的过程遵循完美的零级动力学。体内试验表明，对于30层双层薄膜，该薄膜可以在雄性SD大鼠中维持约20天的血浆药物浓度恒定。口服时血浆药物浓度比峰值血浆药物浓度低2个数量级，日剂量比常用避孕药口服剂量低50倍以上。但是，仍然观察到明显的抗生育作用。此外，未观察到低血钾症，恢复期后可以逆转抗生育作用。结果表明，零级释放可以显着改善棉酚的所需抗生育作用，同时，可以显着降低其副作用。我们设想该药物可以通过零级释放开发成为一种有效，安全和可逆的男性避孕药。
更新日期：2018-01-22
中文翻译：
棉酚的零级释放同时改善了其抗生育作用并减少了其副作用
棉酚被认为是一种有前途的男性避孕药，但由于以下两个副作用而最终失败：低血钾症及其避孕作用的不可逆性。在这里，我们证明持续的零级释放可以解决这些问题。从棉酚/ PEG逐层薄膜中释放棉酚的过程遵循完美的零级动力学。体内试验表明，对于30层双层薄膜，该薄膜可以在雄性SD大鼠中维持约20天的血浆药物浓度恒定。口服时血浆药物浓度比峰值血浆药物浓度低2个数量级，日剂量比常用避孕药口服剂量低50倍以上。但是，仍然观察到明显的抗生育作用。此外，未观察到低血钾症，恢复期后可以逆转抗生育作用。结果表明，零级释放可以显着改善棉酚的所需抗生育作用，同时，可以显着降低其副作用。我们设想该药物可以通过零级释放开发成为一种有效，安全和可逆的男性避孕药。
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