Galactosylated Chitosan Coated Liposomes of Ledipasvir for Liver Targeting: Chemical Synthesis, Statistical Optimization, In-vitro and In-vivo evaluation

Ledipasvir is a novel antiviral agent used in the treatment of hepatitis C. We aim in our study to increase its delivery to hepatocytes and prolong its retention within liver. Several formulae of ledipasvir loaded liposomes were prepared and the best formula regarding particle size, zeta potential, polydispersity index and entrapment efficiency was selected. On the other hand, galactosylated chitosan was synthesized in a chemical reaction. Then the best liposomes formula was coated with the galactosylated chitosan. Having galactose residues on their surface, the coated liposomes can bind to the asialoglycoprotein receptors on the targeted hepatocytes enhancing ledipasvir uptake into them. The galactosylated chitosan coated liposomes had particle size of 218.2 nm +/- 7.21, zeta potential of 27.15 mV +/- 1.76, polydispersity index of 0.278 +/- 0.055 and entrapment efficiency % of 54.63% +/- 0.05 respectively. The pharmacokinetic study revealed a significant increase in the liver peak concentration (C-max) and the area under liver concentration versus time curve AUC((0-72 h) )and significant prolongation in the liver terminal half life (t1/2) and mean residence time (MRT) in comparison to the oral dispersion of ledipasvir with values of 11,400 ng/g, 88,855 ng*h/g, 32.00 h and 18.11 h respectively. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Automated summary

The study successfully enhanced the delivery of ledipasvir to hepatocytes and prolonged its retention within the liver by synthesizing galactosylated chitosan and coating it on liposomes. The coated liposomes exhibited a small particle size, high entrapment efficiency, and significantly improved uptake of ledipasvir into targeted hepatocytes. Pharmacokinetic analysis revealed increased liver concentration and prolonged half-life and residence time compared to oral dispersal of ledipasvir.