| Mucosal surfaces are the most common and convenient routes for administrating therapeutic agents locally or systematically and calcium plays a crucial role in forming the apical junctional complex that preserves epithelial barrier function. Previously, our group have synthesized a new surfactant Pa-Brij78, a pamidronate (Pa) modified Brij78 (polyoxyethylene 20 stearyl ether), which displayed a strong affinity to calcium ions (Ca2+). In this study, we aimed to design a mucoadhesive, calcium reducing chitosan (CS) -coated solid lipid nanoparticles (CS-Pa-SLN), which can improve mucosal drug absorption and penetration. To this end, the hydrophobic curcumin loaded CS-Pa-SLNs were prepared by one-step micro-emulsion template method using CS aqueous solution as a water phase and Pa-Brij78 as a surfactant. CS-Pa-SLNs were characterized by size of 180 nm and a positive charge. The TEM data confirmed the core-shell structure of CS-Pa-SLN.CS-Pa-SLNs were confirmed to be mucoadhesive by in vitro and ex vivo studies. The effect of chitosan (CS)-coated solid lipid nanoparticles (CS-Pa-SLNs) on mucoadhesive in vitro was evaluated by the interaction of nanoparticles with simulation of artificial mucosa glass (Mucosa-plate), soluble mucin and intestinal. The mucoadhesive binding ratio of 0.1%CS-Pa-SLNs and 0.2%CS-Pa-SLNs in vitro adhesion experiments of mucosa-plate is above 60%, soluble mucin is above 80% and rat intestinal is also above 60%, respectively. They are significantly higher than that of regular SLNs and Pa-SLNs.Furthermore, the results showed that CS-Pa-SLNs with the surfactant concentration up to 25 μM did not induce cytotoxicity to Caco-2 cells, suggesting good biocompatibility. Furthermore, the CS-Pa-SLNs produced an enhancement of paracellular permeability compared to non-coated SLNs. In conclusion, our data indicated that CS-Pa-SLNs had both mucoadhesive and penetration enhancement properties and could be used for delivery of hydrophobic drugs through mucosal route. |
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