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与男性避孕药物RISUG作用相关的聚电解质聚合物特性

Polyelectrolyte polymer properties in relation to male contraceptive RISUG action.

作者信息

Roy Sohini, Ghosh Debidas, Guha Sujoy K

机构信息

School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, West Bengal, India.

出版信息

Colloids Surf B Biointerfaces. 2009 Feb 15;69(1):77-84. doi: 10.1016/j.colsurfb.2008.11.002. Epub 2008 Nov 13.

DOI:10.1016/j.colsurfb.2008.11.002
PMID:19111447
Abstract

RISUG a polyelectrolytic hydrogel (styrene maleic anhydride and dimethyl sulfoxide) has proven to be efficacious as a contraceptive for a long term when injected into the lumen of vas deferens. Currently it is in advanced phase III clinical trials in India. Present investigation analyzes the swelling characteristics of RISUG hydrogel in different pH buffers and various biological fluids to understand its retention in the vas deferens as reported in previous studies. Significant variation in degree of swelling and equilibrium swelling ratio with transformation of Fickian to non-Fickian mode of diffusion was observed with increased pH. This might be due to ionization of carboxylic groups at high pH resulting in increased electrostatic repulsive force and high osmotic pressure inside the hydrogel network affecting its physical cross-linking and increases the free volume. Conversely, at low pH the dissociation of carboxylic group is limited making the hydrogel more stable. Interaction with various biomolecules present in various biological fluids was also studied. SEM, AFM and FTIR were used to analyze the topological and structural parameters of the polymer in different mediums. Loosening of structure and increasing porosity with significant adsorption of various biomolecules was observed. AFM revealed a significant change in overall roughness of polymer surface on interaction with different biological fluids. These observations suggest that the swelling and increased roughness will lead to increased resistance to sperm movement in the vas deferens.

摘要

RISUG是一种聚电解质水凝胶(苯乙烯马来酸酐和二甲基亚砜),已被证明当注入输精管腔时可作为一种长效避孕药。目前它正在印度进行三期临床试验。本研究分析了RISUG水凝胶在不同pH缓冲液和各种生物流体中的溶胀特性,以了解其在输精管中的滞留情况,如先前研究所报道的那样。随着pH值升高,观察到溶胀度和平衡溶胀率发生显著变化,扩散模式从菲克扩散转变为非菲克扩散。这可能是由于高pH值下羧基的电离导致静电排斥力增加,以及水凝胶网络内部的高渗透压影响其物理交联并增加了自由体积。相反,在低pH值下,羧基的解离受到限制,使水凝胶更稳定。还研究了与各种生物流体中存在的各种生物分子的相互作用。使用扫描电子显微镜(SEM)、原子力显微镜(AFM)和傅里叶变换红外光谱(FTIR)分析聚合物在不同介质中的拓扑和结构参数。观察到结构松弛和孔隙率增加,同时各种生物分子有显著吸附。原子力显微镜显示,聚合物表面与不同生物流体相互作用时,整体粗糙度发生显著变化。这些观察结果表明,溶胀和粗糙度增加将导致输精管中精子运动的阻力增加。

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