Gupta Kavita M, Barnes Scott R, Tangaro Rachel A, Roberts Meredith C, Owen Derek H, Katz David F, Kiser Patrick F
Department of Bioengineering, University of Utah, Biopolymers Research Building, 20 S. 2030 E. Salt Lake City, Utah 84112, USA.
J Pharm Sci. 2007 Mar;96(3):670-81. doi: 10.1002/jps.20752.
Microbicides are drug delivery systems (DDSs) for the prevention of sexual transmission of HIV and other STDs. A topically applied vaginal microbicidal gel should provide uniform coating of vaginal tissue, retention of this gel layer prior to intercourse, and controlled release kinetics of antivirals to inactivate the viral load potentially introduced during sexual activity. Here, we describe the microbicide-oriented characterization of a DDS made with a dual pH sensitive and thermosensitive smart polymer gel composed of a random terpolymer of N-isopropyl acrylamide, butyl methacrylate, and acrylic acid. The system was engineered to coat vaginal tissue with a stable gel layer and to release entrapped model agents in a burst release profile in response to the presence of the infecting agent: semen. The gel rheology, layer erosion properties, model drug release kinetics, and cytocompatibility of the terpolymer system were studied. Negligible erosion of the gel in the presence of vaginal fluid simulant suggests prolonged retention. Burst release of molecular and macromolecular model compounds was observed when the system's pH changed from the vaginal pH to the pH of semen, and cytotoxicity studies showed that the terpolymer is equally cytocompatible as a commonly used polymeric vaginal carrier.
杀微生物剂是用于预防艾滋病毒和其他性传播疾病性传播的药物递送系统（DDS）。局部应用的阴道杀微生物凝胶应能均匀覆盖阴道组织，在性交前保持该凝胶层，并使抗病毒药物具有可控的释放动力学，以灭活性活动期间可能引入的病毒载量。在此，我们描述了一种由N-异丙基丙烯酰胺、甲基丙烯酸丁酯和丙烯酸的无规三元共聚物组成的具有双重pH敏感性和热敏性的智能聚合物凝胶制成的DDS的面向杀微生物剂的特性。该系统经设计可在阴道组织上形成稳定的凝胶层，并根据感染源精液的存在以突发释放模式释放包封的模型药物。研究了该三元共聚物系统的凝胶流变学、层侵蚀特性、模型药物释放动力学和细胞相容性。在阴道液模拟物存在下凝胶的侵蚀可忽略不计，表明其保留时间延长。当系统的pH从阴道pH值变为精液pH值时，观察到分子和大分子模型化合物的突发释放，细胞毒性研究表明该三元共聚物与常用的聚合物阴道载体具有同等的细胞相容性。
