Oral insulin delivery, the challenge to increase insulin bioavailability: Influence of surface charge in nanoparticle system

Publication date: 5 May 2018 Source:International Journal of Pharmaceutics, Volume 542, Issues 1–2 Author(s): Elodie Czuba, Mouhamadou Diop, Carole Mura, Anais Schaschkow, Allan Langlois, William Bietiger, Romain Neidl, Aurélien Virciglio, Nathalie Auberval, Diane Julien-David, Elisa Maillard, Yves Frere, Eric Marchioni, Michel Pinget, Séverine Sigrist Oral administration of insulin increases patient comfort and could improve glycemic control thanks to the hepatic first passage. However, challenges remain. The current approach uses poly (d, lactic-co-glycolic) acid (PLGA) nanoparticles (NPs), an effective drug carrier system with a long acting profile. However, this system presents a bioavailability of less than 20% for insulin encapsulation. In this context, physico-chemical parameters like surface charge could play a critical role in NP uptake by the intestinal barrier. Therefore, we developed a simple method to modulate NP surface charge to test its impact on uptake in vitro and finally on NP efficiency in vivo. Various NPs were prepared in the presence (+) or absence (−) of polyvinyl alcohol (PVA), sodium dodecyl sulfate (SDS), and/or coated with chitosan chloride. In vitro internalization was tested using epithelial culture of Caco-2 or using a co-culture (Caco-2/RevHT29MTX) by flow cytometry. NPs were then administered by oral route using a pharmaceutical complex vector (100 or 250 UI/kg) in a diabetic rat model. SDS-NPs (−42 ± 2 mV) we...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research