Galactosylated Micelles for a Ribavirin Prodrug Targeting to Hepatocytes

Polymeric micelles potentially able to carry tohepatocytes a ribavirin (RBV) prodrug, exploiting the presenceof carbohydrate receptors, that is, ASGPR, were preparedstarting from a galactosylated polylactide-polyaminoacidconjugate. This latter was obtained by chemical reaction ofα,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide(PHEA-EDA) with polylactic acid (PLA), andsubsequent reaction with lactose, obtaining PHEA-EDA-PLAGALcopolymer. To enhance the entrapment into obtainednanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in thepresence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained inaqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, thespecificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitiveinhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drugdelivery strategy for the hepatitis C treatment.