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SYSTEMIC LYMPH NODE SPECIFIC AGENTS

全身淋巴结特异性药物

基本信息

批准号：
6645279
负责人：
MIKHAIL I PAPISOV
金额：
$ 10万
依托单位：
NANOPHARMA, CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-04-15 至 2006-04-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6645279
关键词：
Yersinia pestis disease anthrax antibacterial agents antibiotics bioterrorism /chemical warfare drug delivery systems drug design /synthesis /production fluorescence microscopy fluorescence spectrometry laboratory rat phagocytes pharmacokinetics quinoline tetracyclines tularemia

项目摘要

DESCRIPTION (provided by applicant): This is an amended application 1 R41 AI052921-01. The overall goal of this project is to develop new targeted formulations of antibiotics for prevention and treatment of diseases caused by Category A pathogens, in particular Bacillus anthracis (anthrax), Yersinia pestis (plague), and Francisella tularensis (tularemia). These preparations will specifically accumulate inside and or in the near vicinity of cells harboring such pathogens after exposure to weaponized (aerosolized) biological agents. Availability of such preparations will provide new strategies of disease prevention for those at risk of exposure, and novel effective treatments for those already infected. The proposed new formulations will be based on lymph node-specific nanocarriers developed at Massachusetts General Hospital. These carriers are capable of transporting various drug substances to lymph node phagocytes (primary pathogen-harboring cells) after systemic administration. It is expected that delivery of antibiotics by such carriers will result in much higher drug levels in the infected lymph node tissue than conventional preparations of the same antibiotics. Thus, the primary site of germination and development of weaponized biological agents will be sufficiently saturated with drugs to prevent or stop disease development at the very early stage (before the onset of symptoms). The objective of this project is to test feasibility of previously established nanocarrier technology for loading lymph node phagocytes with two model antibiotics (one of Fluoroquinolone and one of Tetracycline families), and to develop two respective prototype preparations for further characterization and optimization. The specific aims are: (1) develop two prototype lymph node specific preparations (of Ciprofloxacin and Tetracycline); (2) investigate, in a rodent model, the degree of drug accumulation inside and in the near vicinity of target cells, and (3) evaluate efficacy in infected cells. If successful, this project will result in the development of a new class of preparations and a new strategy for prophylactic and early post-exposure treatment of bacterial diseases of Category A.

描述（由申请人提供）：这是一份经修订的申请1 R41 AI 052921 -01。该项目的总体目标是开发新的抗生素靶向制剂，用于预防和治疗A类病原体引起的疾病，特别是炭疽杆菌（炭疽）、鼠疫耶尔森菌（鼠疫）和土拉热弗朗西斯菌（土拉菌）。这些制剂在接触武器化（雾化）生物制剂后，会特别在含有这些病原体的细胞内部和/或附近积聚。这种制剂的可用性将为那些有接触风险的人提供新的疾病预防策略，并为那些已经感染的人提供新的有效治疗方法。拟议的新制剂将基于马萨诸塞州总医院开发的淋巴结特异性纳米载体。这些载体能够在全身给药后将各种药物转运至淋巴结吞噬细胞（原发性病原体携带细胞）。预期通过这样的载体递送抗生素将导致感染的淋巴结组织中的药物水平比相同抗生素的常规制剂高得多。因此，武器化生物制剂的萌芽和发展的主要场所将充分充满药物，以便在非常早期的阶段（在症状出现之前）预防或阻止疾病的发展。本项目的目的是测试先前建立的纳米载体技术的可行性，用于负载淋巴结吞噬细胞与两种模型抗生素（氟喹诺酮类和四环素家族之一），并开发两种相应的原型制剂，以进一步表征和优化。具体目标是：（1）开发两种原型淋巴结特异性制剂（环丙沙星和四环素）;（2）在啮齿动物模型中研究靶细胞内部和附近的药物积累程度;和（3）评价在感染细胞中的功效。如果成功，该项目将导致开发一类新的制剂和A类细菌性疾病预防和早期暴露后治疗的新策略。