MODELS FOR TESTING CANDIDATE TOPICAL MICROBICIDES FOR CYTOTOXICITY AND ACTIVITY A

测试候选外用杀菌剂细胞毒性和活性 A 的模型

• 批准号: 7337016
• 负责人: MARY F LAMPE
• 金额: $ 21.14万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7337016
• 关键词: Adenocarcinoma Cell; AlamarBlue; Albumins; Antimicrobial Cationic Peptides; Attention; Binding; Biological Assay; Cell Line; Cells; Cervix carcinoma; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Clinical; Coitus; Colorectal Adenocarcinoma; Cytolysis; Development; Drug Formulations; Ectopic Pregnancy; Environmental Risk Factor; Epithelial Cells; Exposure to; Fibroblasts; Glycerol; Goals; HIV; Hela Cells; Human; Human Milk; In Vitro; Infection; Infertility; Laboratories; Lactate Dehydrogenase; Life; Lipids; Local Microbicides; Malignant Epithelial Cell; Measures; Metabolic; Methods; Modeling; Mus; Numbers; Organism; Pelvic Inflammatory Disease; Peptides; Phase; Placebos; Prevention; Reporting; Research; Resistance; Resistance development; Risk; Safety; Seminal fluid; Sexually Transmitted Diseases; Simulate; Testing; Time; Tissues; Vagina; Variant; antimicrobial drug; cytotoxicity; extracellular; in vitro Assay; in vitro Model; in vivo; in vivo Model; membrane activity; microbicide; nonhuman primate; novel; obligate intracellular parasite; pathogen; prevent; prototype; rectal; transmission process; vaginal fluid

DESCRIPTION (provided by applicant): Chlamydia trachomatis, an obligate intracellular parasite, is the most common sexually transmitted bacterial pathogen in the world. Infections are often asymptomatic and can cause serious complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy. In addition, chlamydial infections may increase the risk of human immunodeficiency virus (HIV) transmission. The development of topical microbicides to prevent sexually transmitted infections has recently gained attention. We have developed the in vitro minimal cidal concentration (MCC) assay to test the direct action of microbicides on the extracellular, infectious chlamydial EBs. We now propose to continue developing the MCC assay by studying the in vitro safety and efficacy of peptide and lipid topical microbicides and the effects of strain variation and the presence of human albumin, simulated vaginal fluid, or simulated semen. The MCC assay will further be employed to analyze the effect of novel antimicrobial agents, placed in formulation with universal placebo singly or in combination, for their activity against C. trachomatis. Finally, we will examine safe and active selected formulations of candidate topical microbicides in vivo in a non-human primate model for vaginal and rectal safety and efficacy. The mode of action of anti-chlamydial microbicides on the organism will be assessed as well as the possibility of C. trachomatis strains developing resistance to the selected microbicides. By providing these highly specialized laboratory tests and expertise not readily available in other laboratories, the chlamydia laboratory will contribute fundamentally to topical microbicide research which will ultimately help to prevent HIV and chlamydial infections around the world.

描述（由申请人提供）：沙眼衣原体是一种专性细胞内寄生虫，是世界上最常见的性传播细菌病原体。感染通常是无症状的，可引起严重的并发症，如盆腔炎，不孕症和异位妊娠。此外，衣原体感染可能会增加人类免疫缺陷病毒（HIV）传播的风险。开发局部杀微生物剂以预防性传播感染最近引起了人们的关注。我们开发了体外最小杀菌浓度（MCC）测定法，以测试杀微生物剂对细胞外感染性衣原体EB的直接作用。我们现在建议通过研究肽和脂质局部杀微生物剂的体外安全性和有效性以及菌株变异和人血白蛋白、模拟阴道液或模拟精液的存在的影响，继续开发MCC试验。MCC测定将进一步用于分析单独或组合置于具有通用安慰剂的制剂中的新型抗微生物剂对C.沙眼最后，我们将在非人灵长类动物模型中检查安全和活性的候选局部杀微生物剂的选定制剂在体内的阴道和直肠安全性和有效性。将评估抗衣原体杀微生物剂对微生物的作用方式以及C。沙眼菌株对选定的杀微生物剂产生耐药性。通过提供这些高度专业化的实验室检测和其他实验室不容易获得的专业知识，衣原体实验室将从根本上促进局部杀微生物剂研究，最终有助于预防世界各地的艾滋病毒和衣原体感染。