SMART Polymer Fibers For Tampon-Like Nonsteroidal Contraceptive Devices

项目摘要/摘要 自然生育需要精子通过粘弹性分泌物迁移，并克服生理障碍-- 雌性生殖道的酸性环境。我们的初步数据显示，新型粘附剂， 生物响应性聚合物组合物在暴露于精液时保持生理酸性pH环境 流体，同时，显著增加粘弹性，这对精子运动产生负面影响- 城市。因此，假设在接触精液后，这种新型的粘附性、生物响应性组件- 体位会迅速将阴道腔转变为不适合精子生长的环境。我们建议探索 使用SMART(=系统)为妇女提供按需非类固醇避孕的创新方法 静音直到被远程触发器激活)保持生理的、保护性的拱顶的聚合物纤维- 暴露在精液中会导致不育。这项高风险/高回报的研究 该策略与传统的非类固醇避孕方法有根本的不同，因为它代表了一种 创新的生物工程概念，旨在更快地达到人体测试阶段(即IND里程碑) 而且成本低于专注于药物化学方法的传统开发计划。 在这份行政副刊中，我们将测试是否将用于制药的药物分子- 阴道腔内的逻辑调节改变了工程设计空间和避孕效果 智能聚合物纤维。在目标1中，我们将描述非织造布的电纺工程参数， 含有两亲性杀菌剂的智能纤维垫，具有不同的物理化学性质。我们会 测试它们快速重组为酸性凝胶相的能力，该相具有所需的粘附性和生物活性。 自发性。在目标2中，我们将评估含有杀菌剂的智能纤维的避孕效果 并将结果与无药物智能聚合物纤维进行比较。总的来说，这些结果将定义 智能聚合物纤维临床发展的适应空间，满足女性的喜好。

PROJECT SUMMARY/ABSTRACT Natural fertility requires spermatozoa to migrate through viscoelastic secretions and to overcome the physiolog- ical acidic environment of the female reproductive tract. Our preliminary data show that novel mucoadhesive, bioresponsive polymer compositions maintain a physiologically acidic pH environment upon exposure to seminal fluid and, at the same time, dramatically increase viscoelastic properties, which negatively impacts sperm motil- ity. Therefore, it is hypothesized that - upon exposure to semen - the novel mucoadhesive, bioresponsive com- position rapidly transforms the vaginal cavity into an inhospitable environment for sperm. We propose to explore an innovative approach to on-demand non-steroidal contraception for women using SMART (= System Mute until Activation by a Remote Trigger) polymer fibers that maintain a physiological, protective vag- inal environment upon exposure to seminal fluid resulting in infertility. This high-risk/high-reward research strategy is fundamentally different from conventional nonsteroidal contraceptive methods as it represents an innovative bioengineering concept intended to reach the human testing phase (i.e., IND milestone) much faster and at a lower cost than conventional development programs focusing on medicinal chemistry approaches. In this administrative supplement, we will test whether incorporation of drug molecules intended for pharmaco- logical modulation within the vaginal cavity alters the engineering design space and contraceptive efficacy of SMART polymer fibers. In Aim #1, we will delineate electrospinning engineering parameters for non-woven, SMART fiber mats that contain amphiphilic microbicides exhibiting different physiochemical properties. We will test their ability to rapidly reconstitute into an acidic gel phase that exhibits desired mucoadhesive and biore- sponsive properties. In Aim #2, we will assess contraceptive efficacy of microbicide-containing SMART fiber mats in vitro and compare the results to drug-free SMART polymer fibers. Collectively, these results will define the adaptive space for clinical development of SMART polymer fibers to meet women’s preference.