An estimated 285 million people were living with diabetes in 2010, and this number is expected to reach 440 million by 2030. Current treatment of this disease involves the intradermal injection of insulin analogues. Many alternative administration routes have been proposed, the oral route being the most widely studied. One of the most interesting approaches for insulin delivery is the use of permeation enhancers to increase its transport across the gastrointestinal tract (GIT). Cell‐penetrating peptides (CPPs) are a remarkable example of this family of compounds. Another alternative is the use of medium‐chain fatty acids (MCFAs) to temporally disrupt the tight junctions of the GIT, thereby allowing greater drug transport. A combination of both strategies can provide a synergistic way to increase drug transport through the GIT. In this study we evaluated the complexation of insulin glulisine, an insulin analogue administered subcutaneously or intravenously in clinical practice, with a well‐known CPP modified with the MCFA lauric acid. We prepared several formulations, examined their stability, and tested the best candidates in an intestinal cell‐based model. In particular, two compounds (C₁₂‐r₄ and C₁₂‐r₆) were found to significantly increase the transport of insulin, and therefore show promise as a new delivery system worthy of further evaluation.

中文翻译：

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d-聚精氨酸脂肽作为肠道渗透促进剂

据估计，2010年有2.85亿人患有糖尿病，预计到2030年，这一数字将达到4.4亿。目前对该病的治疗涉及皮内注射胰岛素类似物。已经提出了许多替代的给药途径，口服途径是研究最广泛的。胰岛素递送最有趣的方法之一是使用渗透促进剂来增加其在胃肠道（GIT）中的运输。细胞穿透肽（CPPs）是该化合物家族的杰出代表。另一种替代方法是使用中链脂肪酸（MCFA）暂时破坏GIT的紧密连接，从而实现更大的药物转运。两种策略的组合可以提供一种协同方式，以增加通过GIT的药物运输。在这项研究中，我们评估了临床上通过皮下或静脉内给药的胰岛素类似物谷胱甘肽与MCFA月桂酸修饰的众所周知的CPP的配合。我们准备了几种制剂，检查了它们的稳定性，并在基于肠细胞的模型中测试了最佳候选药物。特别是两种化合物已发现₁₂ -r ₄和C ₁₂ -r ₆）显着增加了胰岛素的运输，因此显示出有望作为值得进一步评估的新的递送系统。