Reduced hepatic toxicity, enhanced cellular uptake and altered pharmacokinetics of stavudine loaded galactosylated liposomes

The aim of the present investigation was to reduce the hepatic toxicity, enhance the cellular uptake and alter the pharmacokinetics of stavudine using galactosylated liposomes. β-d-1-Thiogalactopyranoside residues were covalently coupled with dimyristoyl phosphatidylethanolamine, which was then used to form liposomes. The galactosylated liposomal system was assessed for in vitro ligand-specific activity. The drug release from liposomes was studied by dialysis method. Ex vivo cellular uptake study was performed using liver parenchymal cells harvested from male albino rats. Changes in hematological parameters, hepatic enzymes, hepatomegaly, plasma and tissue distribution of the formulations (free stavudine solution, uncoated liposomal and galactosylated liposomes) were determined using albino rats. Percent cumulative drug release in 24 h was low (34.8 ± 2.6%). Enhanced hepatic cellular d4T uptake (27.96 ± 2.41 pg d4T/million cells) was seen in case of galactosylated liposomal d4T. Galactosylated liposomes maintained a significant level of d4T in tissues rich in galactose specific receptors and had a prolonged residence (11.44 ± 1.25 h) in the body resulting in enhanced half-life of d4T (23.07 ± 1.25 h). This formulation did not show either hematological or hepatic toxicity. Galactosylation of liposomes alter the biodistribution of encapsulated drug thereby delivering the drug to cells bearing galactose specific receptors.