张拥军课题组 | BIOMACROMOLECULES
发布人：功能高分子材料教育部重点实验室 发布时间：2018/07/05 浏览次数： 281 次
Zero-Order Release of Gossypol Improves Its Antifertility Effect and Reduces Its Side Effects Simultaneously
Wen, N (Wen, Na)[ 1,2,3,4 ] ; Dong, YS (Dong, Yansheng)[ 1 ] ; Song, R (Song, Rui)[ 1 ] ; Zhang, WP (Zhang, Wenpeng)[ 1 ] ; Sun, C (Sun, Chao)[ 1 ] ; Zhuang, XM(Zhuang, Xiaomei)[ 1 ] ; Guan, Y (Guan, Ying)[ 2,3,4 ] ; Meng, QB (Meng, Qingbin)[ 1 ] ; Zhang, YJ (Zhang, Yongjun)[ 2,3,4 ]
2018, 19(6): 1918-1925 特刊: SI
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 similar to 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 developed to be an effective, safe, and reversible male contraceptive by zero-order its side effects. We envision the drug could be release.