Lecithin/TPGS-based spray-dried self-microemulsifying drug delivery systems: In vitro pulmonary deposition and cytotoxicity
Lecithin/TPGS-based spray-dried self-microemulsifying drug delivery systems: In vitro pulmonary deposition and cytotoxicity
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DOI：
10.1016/j.ijpharm.2015.03.019
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发表时间：
2015-05-15
影响因子：
5.8
通讯作者：
Osman, Rihab
中科院分区：
文献类型：
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作者：
Ishak, Rania A. H.;Osman, Rihab
本工作的目的是开发一种新的固体自微乳化给药系统（SMEDDS），用于难溶性抗癌药物阿托伐他汀（AVT）的肺部给药。微乳液（ME）首先使用肉豆蔻酸异丙酯（IPM）开发，IPM是2种生物相容性表面活性剂的组合：卵磷脂/D-α-生育酚聚乙二醇琥珀酸酯（TPGS）和乙醇作为助表面活性剂。比较了两种不同磷脂酰胆碱（PC）含量的卵磷脂。采用相图、理化表征和稳定性研究对ME区域进行了研究。固体SMEDDS，然后通过喷雾干燥所选择的ME使用的组合的载体组成的糖，亮氨酸作为促渗剂与或不与聚乙二醇（PEG）6000。产量，流动性，粒度和体外肺沉积用于表征喷雾干燥粉末。重构的ME在形态、粒度和粒度分布方面进行表征。对筛选出的微囊藻毒素和SD-SMEDDS配方在肺癌细胞株上进行了体外细胞毒性研究。结果表明，当卵磷脂/TPGS为1：3、卵磷脂/油为1：1、表面活性剂/助表面活性剂为1：1时，微乳液的性能最佳。与较便宜的含有20%PC的卵磷脂相比，用含有100%PC的卵磷脂获得更大的ME面积。通过控制喷雾干燥参数、载体组成和ME脂质与载体的比例，可以制备具有超过70%的可吸入部分的微粒。即使在去除酒精后，ME在模拟肺液中也有效地回收。在固体SMEDDS中同时递送AVT和TPGS大大增强了对肺癌细胞的细胞毒活性。(C)2015 Elsevier B. V.版权所有。
The aim of the present work was to develop a new solid self-microemulsifying drug delivery system (SMEDDS) for the pulmonary delivery of the poorly water-soluble anti-cancer drug atorvastatin (AVT). Microemulsion (ME) was first developed using isopropyl myristate (IPM), a combination of 2 biocompatible surfactants: lecithin/D-alpha-tocopheryl polyethylene glycol succinate (TPGS) and ethanol as co-surfactant. Two types of lecithin with different phosphatidylcholine (PC) contents were compared. Phase diagram, physico-chemical characterization and stability studies were used to investigate ME region. Solid SMEDDS were then prepared by spray-drying the selected ME using a combination of carriers composed of sugars, leucine as dispersibility enhancer with or without polyethylene glycol (PEG) 6000. Yield, flow properties, particle size and in vitro pulmonary deposition were used to characterize the spray-dried powders. Reconstituted MEs were characterized in terms of morphology, particle size and size distribution. In vitro cytotoxicity study was undertaken on lung cancer cell line for the selected MEs and SD-SMEDDS formulae. Results showed that the most satisfactory MEs properties were obtained with 1:3 lecithin/TPGS, 1:1 lecithin/oil and 1:1 surfactant/co-surfactant ratios. A larger ME area was obtained with lecithin containing 100% PC compared to the less expensive lecithin containing 20% PC. By manipulating spray drying parameters, carrier composition and ratio of ME lipids to carrier, microparticles with more than 70% of respirable fraction could be prepared. The ME was efficiently recovered in simulated lung fluid even after removal of alcohol. The concurrent delivery of AVT with TPGS in solid SMEDDS greatly enhanced the cytotoxic activity on lung cancer cells. (C) 2015 Elsevier B.V. All rights reserved.