Yadav Awadh Bihari, Sharma Rolee, Muttil Pavan, Singh Amit Kumar, Verma Rahul Kumar, Mohan Mradul, Patel Sanjay Kumar, Misra Amit
Pharmaceutics Division, Central Drug Research Institute, Lucknow 226 001, India.
Indian J Exp Biol. 2009 Jun;47(6):469-74.
Macrophage responses to infection with Mycobacterium tuberculosis (MTB) and treatment with soluble isoniazid (INH) plus rifabutin (RFB) versus microparticles containing equivalent amounts of drugs were compared. It was investigated whether macrophages driven to alternative activation upon infection with MTB could be rescued to display the classical activation phenotype. It was established that microparticles sustain high levels of drugs in cytosol of macrophages for longer period as compared to soluble drugs. Microparticles co-localized with intracellular bacteria, and induced a variety of innate bactericidal responses, including induction of free radicals, alteration of mitochondrial membrane potential and apoptosis. The data strongly suggest that additional benefit may be derived from the nature of the drug delivery system, which fulfils Koch's dictum 'stimulate the phagocyte' for curing tuberculosis.
比较了巨噬细胞对结核分枝杆菌（MTB）感染以及可溶性异烟肼（INH）加利福布汀（RFB）与含等量药物的微粒治疗的反应。研究了感染MTB后被驱动至替代性活化的巨噬细胞是否可被挽救以表现出经典活化表型。已确定与可溶性药物相比，微粒在巨噬细胞胞质溶胶中维持高水平药物的时间更长。微粒与细胞内细菌共定位，并诱导多种先天性杀菌反应，包括自由基的诱导、线粒体膜电位的改变和细胞凋亡。数据强烈表明，药物递送系统的性质可能带来额外益处，该系统符合科赫的格言“刺激吞噬细胞”以治愈结核病。
