title: Galactosylated micelles for a ribavirin prodrug targeting to hepatocytes.
abstract: Polymeric micelles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors, that is, ASGPR, were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-dl-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, obtaining PHEA-EDA-PLA-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, that is, RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. Liver-targeted RBV tripalmitate-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometric size. By in vitro experiments, the specificity of RBV tripalmitate-loaded PHEA-EDA-PLA-GAL micelles toward HepG2 was demonstrated by using a competitive inhibition assay in the presence of free GAL. This finding raises hope in terms of future micelles-based liver-targeted drug delivery strategy for the hepatitis C treatment.
authors.affiliation: Lab of Biocompatible Polymers, Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Università di Palermo , via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Emanuela F
authors.initials: EF
authors.lastname: Craparo
authors.forename: Daniela
authors.initials: D
authors.lastname: Triolo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pitarresi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D005690:Galactose / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D011355:Prodrugs; D012254:Ribavirin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000998:Antiviral Agents; D008823:Micelles; D011355:Prodrugs; D012254:Ribavirin; D005690:Galactose