The effect of surface charge on oral absorption of polymeric nanoparticles

Abstract

Surface charge plays an important role in determining the interactions of nanoparticles with biological components. Substantial studies have demonstrated that surface charge affects the fate of nanoparticles after intravenous administration; however, few studies have investigated the effect of surface charge on the bioavailability and absorption of nanoparticles after oral administration. In this study, polymeric nanoparticles with a similar particle size and surface polyethylene glycol (PEG) density, but with varying surface charges (positive, negative and neutral), were developed to study the effect of surface charge on the oral absorption of polymeric nanoparticles. The nanoparticles were constructed from polyethylene glycol-block-polylactic acid (PEG-PLA) with the incorporation of lipid components with different charges. Our results suggested that the positive surface charge facilitated the cellular uptake and transport of nanoparticles through both Caco-2 cells in vitro and small intestinal epithelial cells in vivo. The positively charged nanoparticles showed a favorable distribution in the small intestine, and significantly improved the oral bioavailability. This study presents valuable information towards the design of nanoparticles for improved oral drug delivery.

Influence of surface charge on the formulation of elongated PEG-b-PDLLA nanoparticles

“…[28][29][30] Reports on various polymeric nanoparticles indicate better cel-lular uptake and biodistribution for positively charged particles. [31][32][33] Negatively charged particles were usually less toxic 34,35 and more prone to permeate tissues for targeted delivery. 36,37 Internalization pathways have also been linked to surface charge, with positively charged particles tending towards internalization via clathrin receptors, while negatively charged counterparts are prone for caveolae mediated uptake.…”

Cultivation of hMSCs in Human Plasma Prevents the Cytotoxic and Genotoxic Potential of ZnO-NP In Vitro

“…Besides the size and shape, the surface charge and chemistry of the NPs may influence cellular uptake, too. It was shown that positively charged NPs had a higher bioavailability in vitro and in vivo [21]. The uptake of the positively-charged particles is also enhanced compared to their negative counterparts [22].…”

Surface chemistry-mediated modulation of adsorbed albumin folding state specifies nanocarrier clearance by distinct macrophage subsets

“…11a-c), and whether the observed changes in cellular uptake correlate with electrostatic changes. As most cells have a net negative surface charge, the rate of cellular uptake for anionic and neutral nanoparticles is usually lower than that of cationic nanoparticles due to electrostatic repulsion 46,47 . The baseline uptake of pristine PS (PS lacking a protein corona) under serum-free conditions is consistent with this logic.…”