MICROBICIDES IN MODEL SYSTEMS

本项目的长期目标是开发一个 多阶段，临床前实验室系统，可以预测 临床试验中杀微生物剂的有效性和安全性。广泛 将使用性传播疾病（STD）谱，包括 乳头瘤病毒、HIV-1、HSV-2、T.苍白球和衣原体杀菌剂 将首先在体外测试哺乳动物细胞的毒性和有效性 对抗性病然而，最终的问题是， 临床上有用的杀微生物剂可以抑制/破坏 对阴道壁几乎没有或没有毒性。 为此，我们开发了一种独特的模型系统，其中异种移植物 免疫缺陷小鼠中的人类阴道组织提供了一个环境， 类似于人类阴道中普遍存在的。杀微生物剂 我们将初步评估包括C31 G，表面活性剂，两种组分 剂我们将评估结构/活性关系，配方， 和运输系统。壬苯醇醚-9将作为阳性对照。 我们将在本项目中完善的实验室系统应 为今后快速发展更有效和 更安全的杀菌剂。

The long-term objective of this Program Project is to develop a multiphased, preclinical laboratory system which can predict the effectiveness and safety of microbicides in clinical trials. A broad spectrum of sexually transmitted diseases (STDs) will be used including papillomavirus, HIV-1, HSV-2, T. pallidum, and Chlamydia. Microbicides will first be tested in vitro for mammalian cell toxicity and effectiveness against the STDs. However, the ultimate question is whether potential clinically useful microbicide can inhibit/destroy STD pathogens in the human vaginal environment with little or no toxicity to the vaginal wall. To this end, we have developed a unique model system in which xenografts of human vaginal tissue in immune deficient mice provide an environment similar to that which prevails in the human vagina. The microbicide which we shall initially evaluate include C31G, a surface active, two component agent. We shall evaluate structure/activity relationships, formulations, and delivery systems. Nonoxynol-9 will be included as a positive control. The laboratory systems which we shall refine in this project, should provide guidelines for the rapid, future development of more effective and safer microbicides.