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首页> 外文期刊>Pharmaceutical research >Melittin as a permeability enhancer II: in vitro investigations in human mucus secreting intestinal monolayers and rat colonic mucosae.
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Melittin as a permeability enhancer II: in vitro investigations in human mucus secreting intestinal monolayers and rat colonic mucosae.

机译：蜂毒蛋白作为通透性增强剂II：分泌人单层肠粘膜和大鼠结肠粘膜的黏液的体外研究。

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PURPOSE: Melittin has shown potential as a non-cytotoxic absorption enhancer in Caco-2 monolayers. Our objectives were to assess in vitro efficacy and cytotoxicity of melittin in two intestinal permeability models and investigate the potential mechanism by which melittin might enhance gastrointestinal absorption. MATERIALS AND METHODS: The effects of melittin were examined in the mucus-secreting intestinal cell monolayers, HT29-MTX-E12 (E12), using transepithelial electrical resistance (TER), transmission electron microscopy (TEM) and the MTT viability assay. The effects of melittin on TER, permeability and short circuit current (Isc) were also investigated in rat colon mucosae mounted in Ussing chambers. Ion transporting capacity of tissue was measured in response to secretagogues as surrogate markers of cytotoxicity. Melittin stability was examined by a means of a hemolytic assay. The mechanism by which melittin decreases TER across the rat mucosa was examined with a range of enzymatic inhibitors. RESULTS: Apical addition of melittin resulted in a reversible non-cytotoxic concentration-dependent decrease in TER across E12 monolayers, which was independent of the presence of mucus. Apical addition of melittin reduced TER and increased the permeability of [(14)C]-mannitol across rat colonic mucosae. The melittin-induced drop in TER in rat colon was significantly attenuated by W7 suggesting partial mediation by calmodulin. CONCLUSIONS: The rapid and reversible nature of melittin's permeation enhancing properties and its limited cytotoxicity in polarized intestinal epithelia, suggests a potential drug delivery role for the peptide in oral formulations of poorly absorbed drugs.
机译：用途：蜂毒肽已显示出在Caco-2单层中作为非细胞毒性吸收促进剂的潜力。我们的目标是评估蜂毒蛋白在两种肠道通透性模型中的体外功效和细胞毒性，并研究蜂毒蛋白可能增强胃肠道吸收的潜在机制。材料与方法：使用跨上皮电阻（TER），透射电子显微镜（TEM）和MTT活力测定法，在分泌粘液的肠道细胞单层HT29-MTX-E12（E12）中检查蜂毒肽的作用。蜂毒素对TER，通透性和短路电流（Isc）的影响也在安装于Ussings室的大鼠结肠粘膜中进行了研究。响应促分泌素作为细胞毒性的替代标志物，测量组织的离子转运能力。通过溶血测定法检查蜂毒肽的稳定性。用一系列酶抑制剂研究了蜂毒肽降低大鼠粘膜TER的机制。结果：蜂毒肽的顶部添加导致跨E12单层的TER可逆的非细胞毒性浓度依赖性降低，这与粘液的存在无关。顶端添加蜂毒肽减少了TER，并增加了[（14）C]-甘露醇在大鼠结肠粘膜中的渗透性。 W7显着减弱了蜂毒素诱导的大鼠结肠TER的下降，表明钙调蛋白可部分介导调解。结论：蜂毒肽的渗透增强特性的快速和可逆性质及其在极化的肠上皮细胞中有限的细胞毒性表明该肽在吸收不良的口服制剂中具有潜在的药物传递作用。

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