6533b82bfe1ef96bd128ce43

RESEARCH PRODUCT

Galactosylated polymeric carriers for liver targeting of sorafenib

Emanuela F. Craparo ACarla Sardo ARosa Serio BMaria G. Zizzo BMaria L. Bondì CGaetano Giammona ADGennara Cavallaro A

subject

NiacinamideSorafenibBiodistributionPolyestersBiological AvailabilityPharmaceutical ScienceAntineoplastic AgentsPharmacologyKidneyMicellechemistry.chemical_compoundPolylactic acidHepatic cell-targeted carriersmedicineZeta potentialAnimalsLungneoplasmsMicellesDrug CarriersActive targetingPhenylurea CompoundsHepatic cell-targeted carrierGalactoseActive targeting; Galactosylation; Hepatic cell-targeted carriers; Polymeric micellesSorafenibEthylenediaminesdigestive system diseasesMice Inbred C57BLLiverBiochemistrychemistrySettore CHIM/09 - Farmaceutico Tecnologico ApplicativoGalactosylationDrug deliveryPolymeric micellesFemalePeptidesDrug carrierSpleenmedicine.drugConjugate

description

In this paper, we describe the preparation of liver-targeted polymeric micelles potentially able to carry sorafenib to hepatocytes for treatment of hepatocarcinoma (HCC), exploiting the presence of carbohydrate receptors, ASGPR. These micelles 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)-d,l-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, leading to PHEA-EDA-PLA-GAL copolymer. Liver-targeted sorafenib-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometer size and slightly positive zeta potential. Biodistribution studies on mice demonstrated, after oral administration of sorafenib loaded PHEA-EDA-PLA-GAL micelles, the preferential sorafenib accumulation into the liver. This finding raises hope in terms of future drug delivery strategy of sorafenib-loaded micelles targeted to the liver for the HCC treatment.

yearjournalcountryeditionlanguage
2014-01-01International Journal of Pharmaceutics
https://doi.org/10.1016/j.ijpharm.2014.02.047