Transport properties and aggregation phenomena of polyoxyethylene sorbitane monooleate (polysorbate 80) in pig gastrointestinal mucin and mucus
Transport properties and aggregation phenomena of polyoxyethylene sorbitane monooleate (polysorbate 80) in pig gastrointestinal mucin and mucus
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DOI：
10.1021/la701081s
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发表时间：
2007-10-23
期刊：
影响因子：
3.9
通讯作者：
Nyden, M.
中科院分区：
文献类型：
--
作者：
Lafitte, G.;Thuresson, K.;Nyden, M.
胃肠道中的水环境经常需要在适当的药物递送载体中增溶疏水药物分子。药物分子的有效摄取/吸收和全身暴露需要许多过程，其中一个是载体通过黏液层的运输特性。黏液层是生物分子的复杂混合物。其中，粘蛋白负责这一层的凝胶性质。在这项研究中，我们研究了聚氧乙烯山梨糖烷单油酸酯（聚山梨酯80），一种常用的非离子表面活性剂，在水溶液中，在0.25和5%的黏液溶液中，以及在粘液中的扩散。这些测量是使用脉冲场梯度自旋回波核磁共振（PGSE-NMR）技术完成的。我们得出结论，聚山梨酯80是一种非表面活性分子的混合物，它可以在所有研究的系统中自由扩散，而表面活性分子形成胶束结构，其传输性质强烈依赖于环境。聚山梨酯80胶束不与粘蛋白相互作用，即使它们的扩散受到粘蛋白大分子的阻碍。另一方面，由于与其他成分（如脂库）的相互作用，粘液中的运输速度减慢。在本研究的最后一部分，一个疏水核磁共振探针分子已被纳入系统来模拟疏水药物分子。在水溶液中进行的测量表明，探针分子以与聚山梨酯80胶束非常相似的方式运输，表明它们溶解在胶束核心中。粘液的情况更为复杂。探针分子似乎在低浓度的聚山梨酸80下溶解在脂质储存库中，这减缓了它们的运输。随着聚山梨酯80浓度的增加，探针分子的扩散增加，表明六甲基二硅烷在聚山梨酯80胶束核心中持续溶解。
The aqueous environment in the gastrointestinal tract frequently requires solubilization of hydrophobic drug molecules in appropriate drug delivery vehicles. An effective uptake/absorption and systemic exposure of a drug molecule entails many processes, one being transport properties of the vehicles through the mucus layer. The mucus layer is a complex mixture of biological molecules. Among them, mucin is responsible of the gel properties of this layer. In this study, we have investigated the diffusion of polyoxyethylene sorbitane monooleate (polysorbate 80), a commonly used nonionic surfactant, in aqueous solution, in mucin solutions at 0.25 and 5 wt %, and in mucus. These measurements were done by using the pulsed field gradient spin echo nuclear magnetic resonance (PGSE-NMR) technique. We conclude that polysorbate 80 is a mixture of non-surface-active molecules that can diffuse freely through all the systems investigated and of surface-active molecules that form micellar structures with transport properties strongly dependent on the environment. Polysorbate 80 micelles do not interact with mucin even though their diffusion is hindered by obstruction of the large mucin molecules. On the other hand, the transport is slowed down in mucus due to interactions with other components such as lipids depots. In the last part of this study, a hydrophobic NMR probe molecule has been included in the systems to mimic a hydrophobic drug molecule. The measurements done in aqueous solution revealed that the probe molecules were transported in a closely similar way as the polysorbate 80 micelles, indicating that they were dissolved in the micellar core. The situation was more complex in mucus. The probe molecules seem to dissolve in the lipid depots at low concentrations of polysorbate 80, which slows down their transport. At increasing concentration of polysorbate 80, the diffusion of the probe molecules increases indicating a continuous dissolution of hexamethyldisilane in the core of polysorbate 80 micelles.