The Pharmacokinetics\nand Liver-Targeting Evaluation\nof Silybin Liposomes Mediated by the NTCP/OCTN2 Dual Receptors

The disadvantage of a traditional dosage regimen is the\ninability\nto deliver a sufficient drug concentration to the lesion site, which\ncan result in adverse side effects due to nonspecific drug delivery.\nActively targeting hepatic cells is a promising therapeutic strategy\nfor liver disease. In this study, l-carnitine and a targeting\npeptide derived from the hepatitis B virus large envelope protein\nwere used to modify liposomes for drug delivery to the liver through\nthe sodium taurocholate cotransporting polypeptide (NTCP) and the\norganic cation/carnitine transporter 2 (OCTN2) receptors. Silybin\nwas selected as the model drug. The solubility of silybin can reach\n0.3 mg/mL after encapsulation in liposomes. The NTCP-specific and\nOCTN2-accelerated Myrcludex B and l-carnitine dual-modified\nliposomes were validated <i>in vitro</i>. The uptake of\ncoumarin-6 in dual ligand-modified liposomes by hepatocytes was up\nto 2.36 μg/mg compared with unmodified liposomes (1.05 μg/mg).\nThe pharmacokinetics and targeting abilities of various liposome formulations\nwere evaluated in Kunming mice. Targeted liposomes increased the concentration\nof silybin and prolonged the drug’s retention time in the liver.\nThe area under the liver’s pharmacokinetic curve of targeted\nliposomes was twice that of silybin injection, suggesting the promising\napplication potential of silybin-loaded hepatotropic nanovesicles.