Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Division of Molecular Pharmaceutics, Campus Box #7571, 1310 Kerr Hall, Chapel Hill, NC 27599, United States.
Int J Pharm. 2010 Aug 30;396(1-2):99-104. doi: 10.1016/j.ijpharm.2010.06.037. Epub 2010 Jun 25.
Pulmonary delivery of isoxyl may increase drug efficacy by targeting alveolar macrophages which are host cells for Mycobacteria. Isoxyl microparticles (1-2microm) were obtained by antisolvent precipitation and simultaneous spray drying method. The controls were made by mixing isoxyl solution in DMSO with cell culture media. Depending on the drug concentration, either isoxyl solution or nanosuspension was obtained in these controls. In the study, MTT (methylthiazol tetrazolium) and LDH (lactose dehydrogenase) assays were utilized to test cytotoxicity of these particle suspensions or solutions toward macrophages. Isoxyl microparticles and controls in concentrations up to 100microg/ml were not toxic to macrophages. Both isoxyl microparticle suspensions and controls showed bactericidal activity, as estimated by death of mycobacteria inside the macrophages, at a concentration of 5microg/ml.
异噁唑经肺部给药可以通过靶向肺巨噬细胞来提高药物疗效，肺巨噬细胞是分枝杆菌的宿主细胞。采用反溶剂沉淀和同时喷雾干燥法制备粒径为 1-2μm 的异噁唑微球。对照组是将 DMSO 中的异噁唑溶液与细胞培养基混合制成。根据药物浓度，这些对照组中可得到异噁唑溶液或纳米混悬剂。在该研究中，MTT（噻唑蓝）和 LDH（乳酸脱氢酶）检测法被用于检测这些颗粒混悬液或溶液对巨噬细胞的细胞毒性。浓度高达 100μg/ml 的异噁唑微球和对照组对巨噬细胞没有毒性。浓度为 5μg/ml 时，异噁唑微球混悬液和对照组均表现出杀菌活性，这可通过巨噬细胞内分枝杆菌的死亡来估计。
