Wheat germ agglutinin modification of lipid-polymer hybrid nanoparticles: enhanced cellular uptake and bioadhesion

Lipid-polymer hybrid nanoparticles (LPNs) have emerged as promising nanocarriers for oral delivery of poorly water-soluble drugs because they combine the advantages of polymeric and lipid-based nanoparticles. However, rational surface engineering of LPNs to reduce clearance in the gastrointestinal tract and improve bioavailability remains a challenge. Modification of LPNs with wheat germ agglutinin (WGA), a specific bioadhesive material, was hypothesised to increase site-specific adhesion and improve bioavailability. This study focused on the preparation and characterisation of WGA-modified LPNs (WGA-LPNs) for oral delivery of oridonin. WGA-LPNs were produced by incubating synthetic WGA-1,2-dioleoyl-sn-glycero-3-phosphoethanolamine with LPNs, which had been formed using nanoprecipitation. The WGA-LPNs had a particle size of 326.7 +/- 5.2 nm and a zeta potential of -31.8 +/- 1.04 mV. The core-shell structure and the WGA binding were confirmed by immune gold labelling electron microscopy. Approximately 80% of the drug was released from the nanoparticles within 24 h. WGA-LPNs showed efficient binding to both Caco-2 and HT29-MTX cells and underwent receptor-mediated endocytosis, as evidenced by cellular uptake and confocal imaging. In addition, coumarin 6-loaded WGA-LPNs showed enhanced uptake in the ligated intestinal loop model in vivo, probably due to improved bioadhesion to the villi. These results suggested that WGA-LNPs showed increased intestinal bioadhesion and cellular uptake and have the potential to improve the oral delivery of poorly water-soluble drugs.