Mucus as a barrier to the permeability of hydrophilic and lipophilic compounds in the absence and presence of sodium taurocholate micellar systems using cell culture models

Mucus as a barrier to the permeability of hydrophilic and lipophilic compounds in the absence and presence of sodium taurocholate micellar systems using cell culture models
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DOI:
10.1016/s0928-0987(99)00007-x
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发表时间:
1999-07-01
影响因子:
4.6
通讯作者:
O'Driscoll, C
O'Driscoll, C
中科院分区:
医学2区
文献类型:
--
作者:
Meaney, C;O'Driscoll, C

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粘液分泌CaCo-2-Ht 29 GlucH细胞共培养模型的特征在于,并用于检查粘液作为屏障的亲水性和亲脂性化合物的运输在牛磺胆酸钠胶束(NaTC)系统的存在和不存在的影响。TEER测量和使用亲水性marlrers(甘露醇,聚乙二醇(PEGS)900和4000)的渗透性研究表明,共培养模型的细胞旁渗透性大于CaCo-2模型。在pH 7.4时,在两种模型之间观察到模型亲脂性药物-异丙氧芬的转运无差异。然而,在pH 4.5时,当药物高度电离时,跨共培养单层的转运显著降低。NaTC胶束体系对不同细胞培养模型的影响顺序为CaCo-2>CaCo-2-Ht 29 GlucH> Ht 29 GlucH。通过与粘液溶解剂N-乙酰基-L-半胱氨酸孵育去除粘液层后,在共培养模型中增加了NaTC胶束系统的吸收增强潜力。(C)1999 Elsevier Science B. V.保留所有权利。
A mucus secreting CaCo-2-Ht29GlucH cell co-culture model was characterised and used to examine the influence of mucus as a barrier to the transport of hydrophilic and lipophilic compounds in the absence and presence of sodium taurocholate micellar (NaTC) systems. TEER measurements and permeability studies using the hydrophilic marlrers (mannitol, polyethylene glycols (PEGS) 900 and 4000) indicated that the paracellular permeability of the co-culture model was greater than that of the CaCo-2 model. At pH 7.4, no difference in the transport of a model lipophilic drug, dextropropoxyphene, was observed between the two models. However, at pH 4.5, when the drug was highly ionised the transport was significantly lower across the co-culture monolayers. NaTC micellar systems appeared to affect the different cell culture models in the order CaCo-2>CaCo-2-Ht29GlucH>Ht29GlucH. Following removal of the mucus layer by incubation with the mucolytic agent, N-acetyl-L-cysteine, the absorption enhancing potential of NaTC micellar systems was increased in the co-culture model. (C) 1999 Elsevier Science B.V. All rights reserved.