In vitro evaluation of liposomes containing bio-enhancers for the oral delivery of macromolecules
In vitro evaluation of liposomes containing bio-enhancers for the oral delivery of macromolecules
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DOI：
10.1016/j.ejpb.2010.09.002
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发表时间：
2010-11-01
影响因子：
4.9
通讯作者：
Fricker, Gert
中科院分区：
文献类型：
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作者：
Parmentier, Johannes;Hartmann, Felix J.;Fricker, Gert
这项工作的目的是开发一种含有生物增强剂的新型脂质体，用于亲水性大分子的口服递送。该研究重点关注基于 EPC/胆固醇的配方与 TPGS 1000 和 400、胆酰肌氨酸 (CS)、氯化十六烷基吡啶 (CpCl) 和硬脂胺 (SA) 的组合，涵盖各种不同类型的增强剂。大多数测试的脂质体制剂和增强剂在 Alamar Blue (R) 测定中既不显示对细胞活力的影响，也不显示乳酸脱氢酶 LDH 释放的增加。但是，在1 mM浓度下，CpCl在2小时后表现出很强的毒性，TPGS 1000在8小时后显着降低相同浓度的细胞活力。在总脂质浓度为 5 mM 的情况下，只有一种含有 25% CpCl 的脂质体制剂在 8 小时后导致活力下降至 60.0%。在 Caco-2 Transwell (R) 模型中，一种含有 5% TPGS 400 的配方将 FITC-葡聚糖 70 kDa 的渗透性提高了 3.34 +/- 0.62 倍，一种含有 10% CpCl 的配方改善了 3.69 +/- 0.67 倍，另一种含有 10% CS 和 2.5% SA 的配方改善了 3.41 +/- 0.51 倍，且不影响 TER。含有 10% SA 或 25% CpCl 的脂质体使 FITC-葡聚糖的渗透分别增加了 29.02 +/- 5.84 倍和 39.28 +/- 2.10 倍，但也导致 TER 大幅降低。特别是，这三种制剂将 FITC-葡聚糖的渗透性提高了约 3.5 倍，且没有表现出任何细胞毒性或 TER 降低，应该是开发亲水性大分子口服递送系统的安全有效的候选者。 (C) 2010 Elsevier B.V. 保留所有权利。
The aim of this work was to develop a new type of liposomes containing bio-enhancers for oral delivery of hydrophilic macromolecules. The study focused on EPC/cholesterol-based formulations combined with TPGS 1000 and 400, cholylsarcosine (CS), cetylpyridinium chloride (CpCl) and stearylamine (SA) covering a broad range of different types of enhancers. Most of the tested liposomal formulations and enhancers showed neither influence on cell viability in the Alamar Blue (R) assay nor an increase in lactate dehydrogenase LDH release. But, at a concentration of 1 mM, CpCl exhibited a strong toxicity after 2 h, TPGS 1000 reduced the cell viability at the same concentration after 8 h significantly. Only one liposomal formulation with 25% CpCl led to a decrease in viability to 60.0% after 8 h at a total lipid concentration of 5 mM. In the Caco-2 Transwell (R) model, one formulation with 5% TPGS 400 improved the permeation of FITC-dextran 70 kDa 3.34 +/- 0.62-fold, one with 10% CpCl 3.69 +/- 0.67 and one with 10% CS and 2.5% SA 3.41 +/- 0.51-fold without influencing the TER. Liposomes with 10% SA or 25% CpCl increased the permeation of FITC-dextran 29.02 +/- 5.84, respectively 39.28 +/- 2.10-fold, but led also to a strong reduction in the TER. Especially, the three formulations which enhanced the permeation of FITC-dextran around 3.5-fold without showing any cell toxicity or decrease in TER should be safe and effective candidates for the development of an oral delivery system for hydrophilic macromolecules. (C) 2010 Elsevier B.V. All rights reserved.