The effect of delta G on the transport and oral absorption of macromolecules.
The effect of delta G on the transport and oral absorption of macromolecules.
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Delta G 对大分子转运和口服吸收的影响。
DOI：
10.1002/jps.20052
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Eddington,NatalieD
中科院分区：
文献类型：
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作者：
Salama,NohaN;Fasano,Alessio;Thakar,Manjusha;Eddington,NatalieD
三角洲G(ΔG)是透明带毒素(ZOT)的生物活性片段，ZOT是一种吸收促进剂，可逆地开放小肠和脑内皮细胞和内皮细胞的紧密连接。这项研究以大的细胞旁标志物为模型试剂，评估了ΔG在提高大分子的口服生物利用度方面的可能使用。用ΔG(0,100,180μg/ml)检测[14C]菊粉和[14C]PEG4000在Caco-2细胞中的转运。计算了表观渗透系数(Papp)。测定了ΔG(180μg/ml)的体外毒性。SD大鼠十二指肠给药：[14C]菊粉或[14C]PEG4000(30μCi/kg)加ΔG(720μg/kg)/蛋白水解酶抑制剂(PI)。采集血液并分析血浆中的放射性。ΔG(180PEGg/ml)可使[14C]菊粉和[14C]μ-4000Papp值分别增加82.6%和24.4%，且无任何毒性。加入ΔG/PI后，菊粉和PEG4000的Cmax和AUC值均显著增加(p<； 0.05)。然而，菊粉在体内外表现出更大的促进率。这项研究表明，ΔG可能通过调节细胞旁转运来提高大分子(如蛋白质)的口服生物利用度。©2004 Wiley-Liss，Inc.和美国药剂师协会药学杂志93：1310-1319,2004
Delta G (ΔG) is the biologically active fragment of Zonula Occludens Toxin (Zot), an absorption enhancer, that reversibly opens the tight junctions of epithelial and endothelial cells in the small intestine and brain. This study evaluates the possible use of ΔG in enhancing the oral bioavailability of macromolecules using large paracellular markers as model agents. The transport of [14C]Inulin and [14C]PEG4000 was evaluated across Caco-2 cells with ΔG (0, 100, 180 μg/ml). The apparent permeability coefficients (Papp) were calculated. Thein vitrotoxicity of ΔG (180 μg/ml) was assessed. Sprague Dawley rats were dosed intraduodenally (ID) with the following treatments: [14C]Inulin or [14C]PEG4000 (30 μci/kg) w/o ΔG (720 μg/kg)/protease inhibitors (PI). Blood was collected and plasma was analyzed for radioactivity. ΔG (180 μg/ml) increased [14C]Inulin and [14C]PEG4000 Pappby 82.6 and 24.4%, respectively, without any toxicity. After ID administration with ΔG/PI, Cmaxand AUC were significantly (p< 0.05) increased for both Inulin and PEG4000. However, Inulin displayed greater enhancement ratiosin vitroandin vivo. This study suggests that ΔG may be used to enhance the oral bioavailability of macromolecules (e.g., proteins) after coadministration through modulation of paracellular transport. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1310–1319, 2004