Efficient intracellular delivery of rifampicin to alveolar macrophages using rifampicin-loaded PLGA microspheres: effects of molecular weight and composition of PLGA on release of rifampicin
Efficient intracellular delivery of rifampicin to alveolar macrophages using rifampicin-loaded PLGA microspheres: effects of molecular weight and composition of PLGA on release of rifampicin
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DOI：
10.1016/j.colsurfb.2004.03.018
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发表时间：
2004-07-01
影响因子：
5.8
通讯作者：
Terada, H
中科院分区：
文献类型：
--
作者：
Makino, K;Nakajima, T;Terada, H
采用溶剂挥发法，以Shirasu多孔膜（SPG）为载体，制备了利福平（RFP）单分散PLGA微球。微球为球形，其平均直径约为2 μ m。利福平的载药效率与PLGA的分子量有关。采用分子量较低的PLGA可获得较高的载药效率，这可能是由于利福平的氨基与PLGA末端羧基相互作用所致。本研究中使用了乳酸/乙醇酸单体组成为50/50和75/25的PLGA。从使用分子量为20，000的PLGA配制的负载利福平的PLGA微球中，在pH 7.4下观察到最初7天的滞后期后，利福平以几乎恒定的速率释放20天。另一方面，从使用分子量为5000或10，000的PLGA配制的负载利福平的PLGA微球，在最初的10天内释放了几乎90%的微球中负载的利福平。通过使用载利福平的PLGA微球，观察到利福平向肺泡巨噬细胞的高效递送。当将利福平负载的PLGA微球加入细胞培养基中时，发现在肺泡巨噬细胞中掺入的利福平浓度比加入利福平溶液时高近19倍。(C)2004 Elsevier B. V.保留所有权利。
Monodispersed PLGA microspheres containing rifampicin (RFP) have been prepared by solvent evaporation method using a Shirasu porous class (SPG) membrane. The microspheres were spherical and their average diameter was about 2 mum. The loading efficiency of rifampicin was dependent on the molecular weight of PLGA. The higher loading efficiency was obtained by the usage of PLGA with the lower molecular weight, which may be caused by the interaction of the amino groups of rifampicin with the terminal carboxyl groups of PLGA. PLGA with the monomer compositions of 50/50 and 75/25, of lactic acid/glycolic acid, were used in this study. From rifampicin-loaded PLGA microspheres formulated using PLGA with the molecular weight of 20,000, rifampicin was released with almost constant rate for 20 days after the lag phase was observed for the initial 7 days at pH 7.4. On the other hand, from rifampicin-loaded PLGA microspheres formulated using PLGA with the molecular weight of 5000 or 10,000, almost 90% of rifampicin-loaded in the microspheres was released in the initial 10 days. Highly effective delivery of rifampicin to alveolar macrophages was observed by the usage of rifampicin-loaded PLGA microspheres. Almost 19 times higher concentration of rifampicin was found to be incorporated in alveolar macrophages when rifampicin-loaded PLGA microspheres were added to the cell culture medium than when rifampicin solution was added. (C) 2004 Elsevier B.V. All rights reserved.