Effect of Surface Charges on Oral Absorption of Intact Solid Lipid Nanoparticles.

Abstract

Surface charge is a crucial factor that determines the in vivo behaviors of drug nanocarriers following administration via different routes. However, there is still a lack of comprehensive knowledge of how surface charges affect the in vivo behaviors of particles, especially for oral delivery. In this study, solid lipid nanoparticles (SLNs), as model drug nanocarriers, are modified to bear either anionic, cationic, or net neutral surface charges. The effect of surface charges on oral absorption of intact SLNs was investigated by tracking the in vivo transport of the particles. The fluorescent bioimaging strategy exploits the aggregation-caused quenching property to discriminate the particles. Both in vitro and in vivo lipolysis studies confirm slowed-down lipolysis by anionic charges in comparison with both unmodified and net neutral SLNs but accelerated degradation by cationic charges. The scanning of ex vivo tissues and organs reveals limited absorption of unmodified SLNs into the circulation. Nevertheless, all three types of surface charge modifications are able to enhance the oral absorption of intact SLNs with the fastest and highest absorption observed for net neutral SLNs, possibly owing to promoted mucus penetration. Anionic SLNs, though repulsed by the mucus layer, show the second highest absorption owing to enhanced lymphatic transport. The efficacy of cationic charge modification is less significant due to entrapment and retention in mucus layers as well as increased lability to lipolysis. In conclusion, surface charges may serve as initiators to guide the in vivo behaviors and enhance the oral absorption of intact SLNs.