6533b855fe1ef96bd12afecf

RESEARCH PRODUCT

Galactosylated micelles for a ribavirin prodrug targeting to hepatocytes.

Gaetano GiammonaDaniela TrioloGiovanna PitarresiGennara CavallaroEmanuela Fabiola Craparo

subject

Magnetic Resonance SpectroscopyPolymers and PlasticsBioengineeringMicelleAntiviral AgentsBiomaterialschemistry.chemical_compoundNon-competitive inhibitionPolylactic acidRibavirinSpectroscopy Fourier Transform InfraredMaterials ChemistryCopolymerOrganic chemistryHumansProdrugsMicellesChemistrytechnology industry and agricultureGalactoseHep G2 CellsProdrugCarbohydrateCombinatorial chemistryIn vitroLiverSettore CHIM/09 - Farmaceutico Tecnologico ApplicativoGalactosylated polymeric micelles hepatic cell-targeted carriers active targeting ribavirin tripalmitate hepatitis C.Conjugate

description

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.

yearjournalcountryeditionlanguage
2013-05-10Biomacromolecules
10.1021/bm4002409https://pubmed.ncbi.nlm.nih.gov/23621358