Validation of a Human In Vitro Vaginal Irritation Test

人体体外阴道刺激试验的验证

基本信息

批准号：
7220081
负责人：
Seyoum Ayehunie
金额：
$ 21.23万
依托单位：
MATTEK CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-03-16 至 2008-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7220081
关键词：
Acquired Immunodeficiency Syndrome Acute Adherent Culture Adolescent Adult Animal Model Animal Testing Animals Biological Biological Assay Caring Cells Cervix Uteri Chemical Agents Chemicals Chlamydia trachomatis Class Cyanovirin-N Data Dendritic Cells Development Drug Formulations Economics Electrical Resistance Enzyme-Linked Immunosorbent Assay Epidemic Epithelial Epithelium Ethical Issues Evaluation Exposure to Female Feminine Gel Gender HIV HIV-1 Heterosexuals Histology Human Human Volunteers Hygiene In Vitro Industry Infection Inflammation Institution Lead Life Local Microbicides Macaca Macaca mulatta Materials Testing Measurement Methods Microbe Modeling National Institute of Allergy and Infectious Disease Numbers Oryctolagus cuniculus Pharmacologic Substance Phase Public Health Reliance Reporting Reproducibility Research Research Project Grants Retroviridae Risk Risk Assessment Rivers SIV Safety Screening procedure Seminal fluid Sexuality Sexually Transmitted Diseases Site Spermatocidal Agents Statistical Methods Stratification Switzerland System Testing Time Tissue Model Tissue Viability Tissues Topical application Toxic effect Toxicity Tests United States National Institutes of Health Vagina Validation Woman Women&apos s Health World Health Organization base cost cytokine hazard human tissue in vitro Assay in vivo irritation lymph nodes microbicide monolayer mouse model novel nucleoside analog pre-clinical prevent rectal reproductive research study response sex species difference transmission process vaginal transmission

项目摘要

DESCRIPTION (provided by applicant): Exposure of female reproductive tract to the various chemical agents contained within spermicides, medicaments, microbicides, feminine hygiene and other vaginal care products (VCP) can cause inflammation or tissue damage and thus endanger the health of women. Perturbation of the vaginal epithelium by VCP can also increase the risk of acquiring sexually transmitted infections including HIV-1. Current vaginal irritation/toxicity tests are primarily performed using animal models which are time consuming and costly. Furthermore, results from the most commonly used rabbit vaginal toxicity model do not always correlate with human responses. To date, no validated, human in vitro vaginal irritation method exists. This research project will develop such a test method. Phase I research will prevalidate MatTek's organotypic vaginal-ectocervical (VEC) tissue model for use in identifying potential hazard of existing or newly developed VCP. In vitro assays will include tissue viability, structural damage, barrier function, and cytokine release measurements. Parallel experiments will be performed in an acute rabbit vaginal irritation assay using a well defined set of model test materials. Correlation of the in vivo and in vitro data will result in the development of a sensitive and reliable in vitro vaginal irritation test method. During Phase II, the test method will undergo formal validation in a multi-center, GLP study. A prevalidated in vitro vaginal organotypic tissue model for assessing the irritation potential of chemicals/ formulations will have far reaching application in industries involved in vaginal care products, microbicides, spermicides, and other feminine hygiene and topical pharmaceutical products. Evaluation of irritancy levels is important to minimize hazards in women exposed to topically applied products. The proposed human tissue based assay will provide a sensitive and specific time-efficient method to screen a large number of chemicals/formulations at a reduced cost.

描述（由申请人提供）：女性生殖道暴露于精子剂，药物，杀菌剂，女性卫生和其他阴道护理产品（VCP）中包含的各种化学药物（VCP）可能造成炎症或组织损害，从而危害女性的健康。 VCP对阴道上皮的扰动还可以增加获得包括HIV-1在内的性传播感染的风险。当前的阴道刺激/毒性测试主要使用耗时且昂贵的动物模型进行。此外，最常用的兔阴道毒性模型的结果并不总是与人类反应相关。迄今为止，尚无经过验证的人类体外阴道刺激方法。该研究项目将开发这种测试方法。第一阶段的研究将使Mattek的细胞型阴道宫颈（VEC）组织模型用于识别现有或新开发的VCP的潜在危害。体外测定将包括组织活力，结构损伤，屏障功能和细胞因子释放测量。平行实验将使用一组明确的模型测试材料在急性兔阴道刺激测定中进行。体内和体外数据的相关性将导致发展敏感且可靠的体外阴道刺激测试方法。在第二阶段，测试方法将在多中心的GLP研究中进行正式验证。用于评估化学/制剂的刺激潜力的流行的体外阴道器官组织模型将在与阴道护理产物，微生物剂，杀精子剂以及其他女性卫生和局部制药产品的行业中相远。评估刺激水平对于最大程度地减少暴露于局部应用产品的妇女的危害很重要。提出的基于人体组织的测定将提供一种敏感且特定的时间效率方法，以降低的成本筛选大量化学物质/制剂。