GANGADHARAM, PATTISAPU R

GANGADHARAM, 帕蒂萨普尔

• 批准号: 2068894
• 负责人: PATTISAPU R GANGADHARAM
• 金额: $ 26.87万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2068894
• 关键词: AIDS therapy; Mycobacterium avium; antibacterial agents; combination chemotherapy; drug administration rate /duration; drug adverse effect; host organism interaction; laboratory mouse; liposomes; microorganism disease chemotherapy; monocyte; nonhuman therapy evaluation; opportunistic infections; streptomycin; tissue /cell culture

Mycobacterium avium-intracellulare complex (MAC) causes serious disseminated bacterial infection in patients with the acquired immunodeficiency syndrome (AIDS). MAC infection in AIDS patients is largely resistant to currently available antimycobacterial drugs. These pathogens localize primarily in the macrophages of the reticuloendothelial system (RES). Liposomes are phospholipid vesicles that can encapsulate antibiotics, and are avidly taken up by the RES. Based on previous studies indicating the superior efficacy of several liposome-encapsulated antibiotics against MAC infections in beige mice and cultured macrophages, the central hypothesis of this projects is that targeting antibiotics to the intracellular sites of MAC infection increases their efficacy and reduces their toxicity. The proposed research will establish targeted therapy of MAC in beige mice, an established animal model of this disease. The optimal dose, schedule of administration and combination of liposome- encapsulated antibiotics, including streptomycin, amikacin and clofazimine, will be determined, to achieve maximal antimycobacterial effects in MAC-infected beige mice. The in vivo therapeutic effect of promising new drugs encapsulated in liposomes, including ciprofloxacin, sparfloxacin and clarithromycin, will be investigated. The effect of liposome-encapsulated antibiotics on the growth of MAC in human peripheral blood monocytes will be investigated, to ascertain whether liposomal delivery enhances the anti-MAC activity of these antibiotics and their combinations, as well as to evaluate other new antimycobacterial drugs.

分枝杆菌捕获型菌群综合体（MAC）导致严重 获得的患者的传播细菌感染 免疫缺陷综合征（AIDS）。 艾滋病患者的MAC感染是 对当前可用的抗菌药物的耐药性。这些 病原体主要位于网状内皮的巨噬细胞中 系统（Res）。脂质体是可以封装的磷脂囊泡 抗生素，并被Res狂热地吸收。 基于以前的 研究表明几个脂质体已封装的优势疗效 针对米色小鼠和培养巨噬细胞中MAC感染的抗生素， 该项目的核心假设是将抗生素靶向 MAC感染的细胞内部位增加了其功效和 降低了它们的毒性。 拟议的研究将建立针对性的 Mac在米色小鼠中的疗法，这是该疾病的既定动物模型。 脂质体的最佳剂量，给药时间表和组合 封装抗生素，包括链霉素，amikacin和 将确定氯富齐胺，以达到最大的抗菌抗细菌 在Mac感染的米色小鼠中的作用。 体内治疗作用 有望封装在脂质体中的新药，包括环丙沙星， Sparfloxacin和Clarithromycin将进行研究。 效果 脂质体封装的抗生素在人外周中的MAC生长 将研究血单核细胞，以确定是否脂质体 递送增强了这些抗生素及其的抗MAC活性 组合以及评估其他新的抗菌药物。