Size selectivity of intestinal mucus to diffusing particulates is dependent on surface chemistry and exposure to lipids.
Size selectivity of intestinal mucus to diffusing particulates is dependent on surface chemistry and exposure to lipids.
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DOI：
10.3109/1061186x.2015.1086359
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发表时间：
2015
影响因子：
4.5
通讯作者：
Carrier RL
中科院分区：
文献类型：
--
作者：
Yildiz HM;McKelvey CA;Marsac PJ;Carrier RL
肠粘液为口服递送的药物载体以及其它颗粒（例如，食物、微生物）。粒度、表面化学和给药介质对粘液屏障性质的相对重要性尚未得到充分表征，但在靶向肠粘膜的递送系统设计中很重要。在这项研究中，多粒子跟踪（MPT）被用来研究20- 500纳米直径的羧酸酯和聚乙二醇（PEG）功能化的聚苯乙烯模型载体通过肠粘液的扩散。探索了暴露于缓冲液中的粘液与部分消化的甘油三酯混合物的影响。当分别在缓冲液和模型进食状态肠内容物中给药时，颗粒在肠粘液中的有效扩散率随着颗粒尺寸的增加而降低，小于和大于在均质介质中的理论（Stokes-Einstein）预期。例如，当给予缓冲液中的粘液与含脂质介质时，随着粒度从100 nm增加至500 nm，有效扩散率降低2.9倍与20倍。用PEG官能化显著降低了对给药培养基中脂质的敏感性。结果表明，颗粒尺寸的减小可能会增加颗粒通过肠粘液屏障的转运，但这些作用强烈依赖于肠内容物和颗粒表面化学。
Intestinal mucus provides a significant barrier to transport of orally delivered drug carriers, as well as other particulates (e.g., food, microbes). The relative significance of particle size, surface chemistry, and dosing medium to mucus barrier properties is not well characterized but important in design of delivery systems targeted to the intestinal mucosa. In this study, multiple particle tracking (MPT) was used to study diffusion of 20- to 500-nm diameter carboxylate- and polyethylene glycol- (PEG-) functionalized polystyrene model carriers through intestinal mucus. The impact of exposure to mucus in buffer vs. a partially digested triglyceride mixture was explored. Effective diffusivity of particles in intestinal mucus decreased with increasing particle size less than and more than theoretically (Stokes-Einstein) expected in a homogenous medium when dosed in buffer and model fed state intestinal contents, respectively. For example, effective diffusivity decreased 2.9- vs. 20-fold with increase in particle size from 100 to 500 nm when dosed to mucus in buffer vs. lipid-containing medium. Functionalization with PEG dramatically decreased sensitivity to lipids in dosing medium. The results indicate that reduction of particle size may increase particle transport through intestinal mucus barriers, but these effects are strongly dependent on intestinal contents and particle surface chemistry.