Improved TB Drug Delivery with Novel Polymeric Carriers

描述（由申请人提供）： 有效控制结核病（TB）目前需要使用长期和繁琐的化疗方案。为了设计可以通过吸入或静脉注射间歇地（即每周一次或更少频率）施用的有效方案，需要严格探索持续药物递送的新方法。聚合物基质样微粒系统的最新进展可以为显着改善抗结核药物的递送提供基础。本申请提出首先使用新开发的聚（醚-酸酐）聚合物开发包封一线抗TB药物的各种组合的微粒，并分析其物理化学性质。之后，将在小鼠中进行广泛的药代动力学（PK）研究，以确定所制备的载药微粒的最佳给药剂量和给药频率。将根据PK分析结果优化微粒设计参数。在最后阶段，申请人将严格确定间歇性聚（醚-酸酐）微粒组合在明确定义的、高度预后的活动性结核病小鼠模型中的疗效，该模型旨在模拟人类疾病的治疗。

DESCRIPTION (provided by applicant): Effective control of tuberculosis (TB) currently requires the use of long and cumbersome chemotherapeutic regimens. In order to design effective regimens that can be administered intermittently (i.e. once-weekly or less often) by inhalation or intravenous injection, novel methods of sustained drug delivery need to be rigorously explored. Recent advances in polymeric matrix-like particulate systems can provide the foundation needed to significantly improve the delivery of antituberculosis drugs. This application proposes to first develop, micropartices encapsulating various combinations of first-line anti-TB drugs using the newly developed poly(ether-anhydride) polymer and to analyze their physicochemical properties. Following that, extensive pharmacokinetic (PK) studies will be conducted in mice to determine the optimal dosage and frequency of administration of the prepared drug-loaded microparticles. Microparticle design parameters will be optimized as indicated by PK analysis. In the final phase, the applicant will rigorously determine the efficacy of intermittent poly(ether-anhydride) microparticle-based combinations in a well-defined, highly prognostic murine model of active tuberculosis designed to mimic the treatment of human disease.