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Khatri, K. et al.

Hepatitis B surface protein docked vesicular carrier for site specific delivery to liver.

The intrinsic liver tropism of liposomes can be augmented by the addition of targeting features such as the incorporation of hepatotropic elements of the hepatitis viruses. Hepatitis B virus is known to infect hepatocytes after viremia by asialoglycoprotein receptor mediated uptake. However, the specificity of hepatitis B virus surface protein (HBsAg) towards hepatocytes has confronting reports. In the present study, we evaluated the functional ability of HBsAg to be employed as a ligand for targeting hepatocytes. We prepared (14)C labeled small unilamellar vesicles (SUVs) composed of egg PC/Cholesterol/N-glutarylphosphatidylethanolamine (NGPE) in a 60:30:10 molar ratio. HBsAg was covalently linked to SUVs using a water-soluble carbodiimide (EDC) mediated conjugation with NGPE. In vitro cell binding and uptake studies revealed that bioprotein docked carrier system was efficiently taken up by HepG2 cells by the receptor mediated endocytosis. The biodistribution behaviour of plain and HBsAg coated liposomes was also examined followed by intravenous injection. The study revealed that almost 75% of the radioactivity was recovered in the liver after 4 h of injection that was nearly three-fold greater in magnitude than the plain liposomes. Further, fractionation of liver into liver parenchymal cells (PC) and non-parenchymal cells confirmed the preferential localization of the HBsAg coated liposomal carrier in the parenchymal cells.[1]

References

Hepatitis B surface protein docked vesicular carrier for site specific delivery to liver. Khatri, K., Rawat, A., Mahor, S., Gupta, P.N., Vyas, S.P. Journal of drug targeting. (2005) [Pubmed]

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