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

Abstract

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.

Targeting strategies with lipid vectors for nucleic acid supplementation therapy in Fabry disease: a systematic review

“…A significantly higher β-galactosidase activity was found in liver relative to other organs, including lung, kidney, skin and heart 24 and 48 h after administration. Hepatitis B virus surface protein (HBsAg) has been used to develop liposomes with strict hepatotropism [58]. The covalently linked to the surface of nanoparticles for active targeting [78,79].…”

Advances in Effective Vaccine Development Against Hepatitis B: Focus on Mucosal Vaccine Delivery Strategies

“…In the infectious condition, HBV particles bind with the plasma membranes of hepatocytes, which is a crucial step of viral entry [18]. The viral envelope is composed of three polypeptides, classified as small, middle and large surface proteins, which play important roles in reorganization of receptors on hepatocytes followed by internalization [20]. Study of the HBV genome demonstrated that basically four genes are encoded by this genome, that is C, X, P and the hepatitis B surface antigen gene.…”

A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

“…Extensive studies have been conducted using HBV as a carrier system [18][19][20] and its surface envelope proteins as delivery systems 17,21,22 or targeting moieties. 23,24 However, their application is severely constrained by the safety of viral carriers 25 and the strong immunogenicity of extrinsic proteins. 26,27 The envelope protein of HBV consists of large (L), middle (M), and small (S) proteins.…”