Faculty of Pharmaceutical Sciences, Tokyo University of Sciences, Noda, Chiba, Japan.
Colloids Surf B Biointerfaces. 2010 Mar 1;76(1):151-7. doi: 10.1016/j.colsurfb.2009.10.036. Epub 2009 Oct 29.
We have developed a pulmonary drug delivery system for the treatment of tuberculosis using rifampicin (RFP) encapsulated in poly-(lactic-co-glycolic acid) microspheres (RFP-PLGA MS), which is a biocompatible polymer. In this study, the behavior of RFP-PLGA MS and the metabolism of RFP were investigated after their uptake by macrophages using the rat alveolar macrophage cell line, NR8383. The prepared RFP-PLGA MS were spherical with an average diameter of 1.9microm and were taken up effectively by NR8383 cells in an energy-dependent manner. It was shown by fluorescent microscopic studies that the RPF-PLGA MS taken up by the cells were localized in phago-lysosomes and then degraded. Although a small amount of 3-formylrifamycin SV (3-FRSV) was generated by the metabolism of RFP, almost all RFP remained unchanged. It was considered, therefore, that RFP was released into the cytosol with drug potency intact. Based on these results, RFP-PLGA MS will be effective for the delivery of anti-tuberculosis drugs such as RFP, and will be a potentially useful drug delivery tool for pulmonary and possibly other tissues as well.
我们已经开发了一种使用利福平（RFP）封装在聚（乳酸-共-羟基乙酸）微球（RFP-PLGA MS）中的肺部药物输送系统，用于治疗结核病，这是一种生物相容性聚合物。在这项研究中，使用大鼠肺泡巨噬细胞系 NR8383 研究了 RFP-PLGA MS 被巨噬细胞摄取后的行为和 RFP 的代谢。制备的 RFP-PLGA MS 呈球形，平均直径为 1.9μm，能够以能量依赖的方式被 NR8383 细胞有效摄取。荧光显微镜研究表明，被细胞摄取的 RPF-PLGA MS 定位于吞噬溶酶体中并随后降解。虽然 RFP 的代谢产生了少量的 3-甲酰利福霉素 SV（3-FRSV），但几乎所有的 RFP 都保持不变。因此，认为 RFP 以完整的药物效力释放到细胞质中。基于这些结果，RFP-PLGA MS 将有效地用于输送利福平等抗结核病药物，并且将成为肺部和可能其他组织的潜在有用的药物输送工具。
