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d-Polyarginine Lipopeptides as Intestinal Permeation Enhancers.
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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.
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GARCIA GARCIA, Josep, FERNÁNDEZ BLANCO, Álvaro, TEIXIDÓ TURÀ, Meritxell, SÁNCHEZ NAVARRO, Macarena, GIRALT LLEDÓ, Ernest. d-Polyarginine Lipopeptides as Intestinal Permeation Enhancers.. _Chemmedchem_. 2018. [consulta: 11 de desembre de 2025]. [Disponible a: https://hdl.handle.net/2445/125041]