Paclitaxel loaded PEG5000-DSPE micelles as pulmonary delivery platform: Formulation characterization, tissue distribution, plasma pharmacokinetics, and toxicological evaluation
Paclitaxel loaded PEG5000-DSPE micelles as pulmonary delivery platform: Formulation characterization, tissue distribution, plasma pharmacokinetics, and toxicological evaluation
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DOI：
10.1016/j.ejpb.2011.04.017
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发表时间：
2011-10-01
影响因子：
4.9
通讯作者：
Kaddoumi, Amal
中科院分区：
文献类型：
--
作者：
Gill, Kanwaldeep K.;Nazzal, Sami;Kaddoumi, Amal
本研究的目的是评估由 PEG(5000)-DSPE 制成的负载紫杉醇的胶束作为肺部递送后的缓释系统的潜力。采用溶剂蒸发技术制备了含紫杉醇的PEG(5000)-DSPE胶束，并考察了紫杉醇在模拟肺液中的体外释放。除了气管内施用紫杉醇外，还研究了气管内和静脉内施用后PEG-脂质胶束的组织分布和血浆药代动力学。最后，研究了 PEG(5000)-DSPE 的毒理学特征。紫杉醇成功配制在 PEG-脂质胶束中，包封率为 95%。 PEG-脂质胶束在模拟肺液中表现出持续释放行为。气管内施用的聚合胶束紫杉醇显示紫杉醇在肺中的累积最高，肺中的AUC(0-12)比静脉内施用的制剂高45倍，比气管内递送的紫杉醇高3倍。其他非靶组织和血浆中的紫杉醇浓度显着低于其他组。此外，毒性研究表明，与盐水治疗组相比，PEG(5000)-DSPE 治疗组的肺损伤标志物水平没有显着增加。气管内递送的 PEG(5000)-DSPE 胶束能够在肺部长时间维持最高的紫杉醇浓度，从而了解它们作为肺部药物载体的适合性。 (C) 2011 Elsevier B.V. 保留所有权利。
The objective of the present study was to evaluate the potential of paclitaxel loaded micelles fabricated from PEG(5000)-DSPE as a sustained release system following pulmonary delivery. PEG(5000)-DSPE micelles containing paclitaxel were prepared by solvent evaporation technique followed by investigation of in vitro release of paclitaxel in lung simulated fluid. Tissue distribution and plasma pharmacokinetics of the PEG-lipid micelles after intratracheal and intravenous administrations were investigated in addition to intratracheally administered taxol. Finally, toxicological profile of PEG(5000)-DSPE was investigated. Paclitaxel was successfully formulated in PEG-lipid micelles with encapsulation efficiency of 95%. The PEG-lipid micelles exhibited a sustained release behavior in the simulated lung fluid. lntratracheally administered polymeric micellar paclitaxel showed highest accumulation of paclitaxel in the lungs with AUC(0-12) in lungs being 45-fold higher than intravenously administered formulation and 3-fold higher than intratracheally delivered taxol. Paclitaxel concentration in other non-targeted tissues and plasma were significantly lower as compared to other groups. Furthermore, toxicity studies showed no significant increase in levels of lung injury markers in PEG(5000)-DSPE treated group as compared to saline-treated group. PEG(5000)-DSPE micelles delivered intratracheally were able to sustain highest paclitaxel concentrations in lungs for long periods of time, thus apprehending their suitability as pulmonary drug carriers. (C) 2011 Elsevier B.V. All rights reserved.