title: Novel composed galactosylated nanodevices containing a ribavirin prodrug as hepatic cell-targeted carriers for HCV treatment.
abstract: In this paper, we describe the preparation of liver-targeted nanoparticles potentially able to carry to hepatocytes a ribavirin (RBV) prodrug, exploiting the presence of carbohydrate receptors in the liver (i.e., ASGPR in hepatocytes). These particles were obtained starting from a galactosylated phospholipid-polyaminoacid conjugate. This latter was obtained by chemical reaction of alpha,beta-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-DL-aspartamide (PHEA-EDA) with 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(succinyl) sodium salt (DPPE), and subsequent reaction with lactose, obtaining PHEA-EDA-DPPE-GAL copolymer. To enhance the entrapment into obtained nanostructures, a hydrophobic RBV prodrug, i.e., RBV tripalmitate, was synthesized and its capability to release RBV in the presence of an adequate enzymatic activity was demonstrated. RBV tripalmitate-loaded nanoparticles were obtained starting from PHEA-EDA-DPPE-GAL copolymer by using the dialysis method. These particles showed spherical shape and nanometric size. By in vitro experiments the absence of haemolytic activity of RBV tripalmitate-loaded PHEA-EDA-DPPE-GAL nanoparticles and their specificity toward HepG2 were demonstrated by using a competitive inhibition assay in the presence of free GAL and assessing nanoparticle uptake in the presence of free GAL and/or non-galactosylated nanoparticles. This finding raises hope in terms of future nanoparticle-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 Fabiola
authors.initials: EF
authors.lastname: Craparo
authors.forename: Girolamo
authors.initials: G
authors.lastname: Teresi
authors.forename: Mariano
authors.initials: M
authors.lastname: Licciardi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Bondí
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry; D004058:Diffusion; D005690:Galactose / Q000737:chemistry* / Q000493:pharmacokinetics*; D056945:Hep G2 Cells; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D008422:Materials Testing; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry; D012254:Ribavirin / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D053769:Nanocapsules; D011355:Prodrugs; D012254:Ribavirin; D005690:Galactose