Validation of a Human In Vitro Vaginal Irritation Test

人体体外阴道刺激试验的验证

• 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
• 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' 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

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）：女性生殖道暴露于杀精剂、药物、杀微生物剂、女性卫生用品和其他阴道护理产品（VCP）中含有的各种化学剂，可引起炎症或组织损伤，从而危及妇女的健康。VCP对阴道上皮的扰动也可增加获得性传播感染（包括HIV-1）的风险。目前的阴道刺激/毒性试验主要是用动物模型进行的，既耗时又昂贵。此外，最常用的兔阴道毒性模型的结果并不总是与人的反应相关。到目前为止，还没有有效的人体外阴道刺激方法存在。本研究项目将开发这样一种测试方法。一期研究将预先验证MatTek的器官型阴道-宫颈外周（VEC）组织模型，用于识别现有或新开发的VCP的潜在危害。体外检测将包括组织活力、结构损伤、屏障功能和细胞因子释放测量。平行实验将在急性兔阴道刺激试验中进行，使用一套定义良好的模型试验材料。体内和体外数据的相关性将导致开发一种敏感可靠的体外阴道刺激试验方法。在第二阶段，测试方法将在多中心GLP研究中进行正式验证。预验证的体外阴道器官型组织模型用于评估化学品/配方的刺激潜力，将在涉及阴道护理产品，杀微生物剂，杀精子剂和其他女性卫生和局部药物产品的行业中具有深远的应用。对暴露于局部应用产品的妇女的刺激程度进行评估是重要的，以尽量减少危害。拟议的基于人体组织的检测将提供一种敏感和特定的时间效率方法，以较低的成本筛选大量化学品/配方。