Selenized Polymer-Lipid Hybrid Nanoparticles for Oral Delivery of Tripterine with Ameliorative Oral Anti-Enteritis Activity and Bioavailability

The oral delivery of insoluble and enterotoxic drugs has been largely plagued by gastrointestinal irritation, side effects, and limited bioavailability. Tripterine (Tri) ranks as the hotspot of anti-inflammatory research other than inferior water-solubility and biocompatibility. This study was intended to develop selenized polymer-lipid hybrid nanoparticles loading Tri ([email protected]) for enteritis intervention by improving its cellular uptake and bioavailability.[email protected]were fabricated by a solvent diffusion-in situ reduction technique and characterized by particle size, ζ potential, morphology, and entrapment efficiency (EE). The cytotoxicity, cellular uptake, oral pharmacokinetics, and in vivo anti-inflammatory effect were evaluated. The resultant[email protected]were 123 nm around in particle size, with a PDI of 0.183, ζ potential of −29.70 mV, andEEof 98.95%.[email protected]exhibited retardant drug release and better stability in the digestive fluids compared with the unmodified counterpart (Tri-PLNs). Moreover,[email protected]manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy. The oral bioavailability of Tri-PLNs and[email protected]was up to 280% and 397% relative to Tri suspensions, respectively. Furthermore,[email protected]demonstrated more potent in vivo anti-enteritis activity, which resulted in a marked resolution of ulcerative colitis. Polymer-lipid hybrid nanoparticles (PLNs) enabled drug supersaturation in the gut and the sustained release of Tri to facilitate absorption, while selenium surface engineering reinforced the formulation performance and in vivo anti-inflammatory efficacy. The present work provides a proof-of-concept for the combined therapy of inflammatory bowel disease (IBD) using phytomedicine and Se in an integrated nanosystem. Selenized PLNs loading anti-inflammatory phytomedicine may be valuable for the treatment of intractable inflammatory diseases.Keywords:tripterine;selenium;polymer-lipid hybrid nanoparticles;bioavailability;enteritis;anti-inflammation