Galactose Liposomes for Liver PC Targeting

PC exclusively expresses large numbers of high affinity cell-surface receptors that can bind asia-loglycoprotein and internalize to the cell interior. In order to achieve PC-specific gene transfection, galactose moieties are introduced into the cationic liposomes. The galactosylation of liposomes can be achieved by coating with either glycoproteins or galactose conjugated synthetic lipids. Hara et al.96 reported that asialofetuin-labeled liposomes encapsulating pDNA were taken up by asialogly-coprotein receptor-mediated endocytosis using cultured PC and showed the highest hepatic gene expression after intraportal injection with a preloading of EDTA. Gal-C4-Chol that possess a similar structure to Man-C4-Chol was synthesized.58 In vivo gene transfer was examined by optimizing the pharmacokinetics and physicochemical properties.97 The radioactivity in the liver from the Gal-liposome/[32P] pDNA complex (Gal-lipoplexes) was about 75% of the dose even 1 min after intraportal administration. The hepatic gene expression of Gal-lipoplexes was more than a 10-fold greater than that of lipoplexes with bare cationic liposomes. When gene expression was examined at the intrahepatic cellular level, the gene expression of PC of Gal-lipoplexes was significantly higher than that of liver NPC. On the other hand, the gene expression of PC and NPC of lipoplexes was almost identical. In addition, asialoglycoprotein receptor-mediated endo-cytosis was also confirmed by the inhibitory effect of pre-dosing an excess amount of galactosylated bovine serum albumin. It was previously reported that the lipoplexes interact with erythrocytes after intravenous administration.88 Recently, the presence of an essential amount of sodium chloride (NaCl) during the formation of Gal-lipoplexes stabilizing the complexes in accordance with the surface charge regulation (SCR) theory was demonstrated.98 The transfection activity in hepato-cytes of SCR Gal-lipoplexes was significantly higher than that of conventional complexes.

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