Sustained oral drug delivery using PEGylated liposomes incorporated into polysaccharide hydrogel formulations

Abstract

In this study, we combined PEGylated liposomes (PEG-Lip) with polysaccharides to sustain the oral absorption-enhancing effect of PEG-Lip. The formulated PEG-Lip had a particle size of ~100 nm and a zeta potential of about −70 mV. The polysaccharides used were carrageenan (CGN), xanthan gum (XG), and locust bean gum (LBG). The polysaccharide concentrations that did not inhibit PEG-Lip behavior varied by type: 0.5% for CGN and 0.25% for XG and LBG. Furthermore, differences in the interactions between each polysaccharide and PEG-Lip may influence PEG-Lip’s behavior within the polysaccharides. In the rheological property evaluation, only XG3-LBG7, a 3:7 mixture of XG and LBG, exhibited gel-like behavior; the others functioned as thickeners. When PEG-Lip-containing polysaccharides were orally administered to rats and their gastrointestinal distribution was evaluated 4 h later, all formulations demonstrated improved gastrointestinal retention compared to PEG-Lip alone. Furthermore, when comparing the oral absorption of PEG-Lip-containing polysaccharide formulations encapsulating FITC-dextran (FD4), XG3-LBG7 provided the greatest improvement in absorption. Our results indicate that optimizing the release properties of PEG-Lip from the formulation and the rheological properties of the polysaccharide are crucial for improving oral absorption and sustaining the efficacy of PEG-Lip.