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: 7500730
• 负责人: MARY F LAMPE
• 金额: $ 20.18万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7500730
• 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，衣原体感染可能增加人类免疫缺陷病毒（HIV）传播的风险。局部杀菌剂的发展，以防止性传播感染最近已引起重视。我们建立了体外最低杀灭浓度（MCC）测定法，以测试杀菌剂对细胞外感染性衣原体EBs的直接作用。我们现在建议通过研究多肽和脂类局部杀微生物剂的体外安全性和有效性，以及菌株变化和人白蛋白、模拟阴道液或模拟精液的存在的影响，继续发展MCC测定。MCC试验将进一步用于分析新型抗菌剂的效果，这些抗菌剂与通用安慰剂单独或联合使用，对沙眼衣原体具有活性。最后，我们将在非人类灵长类动物模型中检查候选局部杀微生物剂在体内的安全性和有效性。将评估抗衣原体杀菌剂对生物体的作用方式，以及沙眼衣原体菌株对所选杀菌剂产生耐药性的可能性。衣原体实验室通过提供其他实验室无法提供的这些高度专业化的实验室检测和专门知识，将对局部杀微生物剂研究作出根本贡献，最终将有助于在世界各地预防艾滋病毒和衣原体感染。