MICROBICIDES IN MODEL SYSTEMS

该计划项目的长期目标是开发一个 多阶段的临床前实验室系统可以预测 杀菌剂在临床试验中的有效性和安全性。一个大女人 将使用的性传播疾病(STD)范围包括 乳头瘤病毒、HIV-1、HSV-2、梅毒螺旋体和衣原体。杀微生物剂 将首先在体外测试哺乳动物细胞的毒性和有效性 对抗性传播疾病。然而，最终的问题是，潜在的 临床上常用的杀微生物剂可以抑制/杀灭性病病原体 人类阴道环境对阴道壁的毒性很小或没有。 为此，我们开发了一种独特的模型系统，在该系统中，异种移植 免疫缺陷小鼠的人阴道组织提供了一个环境 与人类阴道中流行的类似。一种杀微生物剂 我们将初步评估包括C31G，一种表面活性，两种成分 探员。我们将评估结构/活性关系、配方、 和传输系统。作为阳性对照，将包括壬醇-9。 我们将在这个项目中改进的实验室系统应该 为更有效和更高效的未来快速发展提供指导 更安全的杀微生物剂。

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.