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交联聚合物基质对缬沙坦的控释:合成、体外及体内评价

Controlled delivery of valsartan by cross-linked polymeric matrices: Synthesis, in vitro and in vivo evaluation.

作者信息

Sohail Muhammad, Ahmad Mahmood, Minhas Muhammad Usman, Ali Liaqat, Khalid Ikrima, Rashid Haroon

机构信息

Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, 63100 Punjab, Pakistan.

Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, 63100 Punjab, Pakistan.

出版信息

Int J Pharm. 2015 Jun 20;487(1-2):110-9. doi: 10.1016/j.ijpharm.2015.04.013. Epub 2015 Apr 9.

DOI:10.1016/j.ijpharm.2015.04.013
PMID:25865571
Abstract

The purpose of study was to develop chemically cross-linked chitosan-co-poly(AMPS) hydrogel based on low molecular weight chitosan for pH-responsive and controlled drug delivery of a model drug. Cross-linking was achieved chemically, by using free radical polymerization technique. Polymer (low molecular weight chitosan) was chemically cross-linked with monomer (2-acrylamido-2-methylpropane sulfonic acid) in aqueous medium. N, N'-Methylenebisacrylamide (MBA) was used as cross-linking agent. Sodium hydrogen sulfite (SHS) and ammonium peroxodisulphate (APS) were used as initiators in a chemical reaction. Hydrogels were characterized by FT-IR, SEM and DSC. Swelling studies and pH-sensitivity of hydrogels were studies at pH 1.2 and 7.4. Chitosan-co-poly(AMPS) hydrogels were administered to rabbits orally to evaluate its pharmacokinetic behavior. As a result of successful cross-linking of polymer and monomer, novel co-polymer has been developed, having suitable characteristics as desired for controlled release drug delivery system. Maximum swelling, drug loading and release have been observed at pH 7.4. In vivo results exhibited significant drug release and absorption at pH 7.4 in rabbits. It is concluded that highly swelling chitosan-AMPS based hydrogels were developed having pH independent swelling and pH dependent drug release properties. These hydrogels have great potential to be used for loading and controlled release of various therapeutic agents.

摘要

本研究的目的是基于低分子量壳聚糖开发化学交联的壳聚糖-共-聚(AMPS)水凝胶,用于模型药物的pH响应性和控释给药。通过自由基聚合技术实现化学交联。聚合物(低分子量壳聚糖)在水性介质中与单体(2-丙烯酰胺基-2-甲基丙烷磺酸)进行化学交联。N,N'-亚甲基双丙烯酰胺(MBA)用作交联剂。亚硫酸氢钠(SHS)和过硫酸铵(APS)用作化学反应的引发剂。通过傅里叶变换红外光谱(FT-IR)、扫描电子显微镜(SEM)和差示扫描量热法(DSC)对水凝胶进行表征。在pH 1.2和7.4条件下研究了水凝胶的溶胀特性和pH敏感性。将壳聚糖-共-聚(AMPS)水凝胶口服给予兔子,以评估其药代动力学行为。由于聚合物和单体成功交联,开发出了具有控释给药系统所需合适特性的新型共聚物。在pH 7.4时观察到最大溶胀、药物负载和释放。体内结果显示兔子在pH 7.4时药物有显著释放和吸收。结论是开发出了具有pH无关溶胀和pH依赖药物释放特性的高溶胀性壳聚糖-AMPS基水凝胶。这些水凝胶在负载和控释各种治疗剂方面具有巨大潜力。

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