This study demonstrates the preparation of a silybin-loaded N-octyl-O, N-carboxymethyl chitosan micelle (OCC-SLB) to enhance the oral absorption efficiency of silybin (SLB) and investigate the related mechanisms of enhancement. Firstly, the physicochemical properties of OCC and OCC-SLB micelles, including critical micelle concentration (CMC), particle size, zeta potential, drug-loading, etc., were determined. Results of pharmacokinetic studies on rats then confirmed a desirable enhancement in the oral bioavailability of SLB by OCC-SLB micelles compared with a stock SLB suspension solution. Subsequently, uptake studies on the Caco-2 cell line demonstrated that OCC-SLB micelles effectively accumulated SLB or rhodamine-123 into cells through clathrin and caveolae-mediated endocytosis and the inhibition of P-glycoprotein (P-gp) efflux. In addition, results of the Caco-2 transport study further clarified that OCC-SLB micelles enhanced the permeability of SLB via tight junction opening and clathrin-mediated transcytosis across the endothelium. These findings indicated the OCC micelle platform as a potential delivery vehicle for oral administration of P-gp substrates such as SLB.
Keywords: Mechanism; Micelles; N-octyl-O, N-carboxymethyl chitosan; Oral administration; Silybin.
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