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Galactosylated polymeric carriers for liver targeting of sorafenib

2014; Elsevier BV; Volume: 466; Issue: 1-2 Linguagem: Inglês

10.1016/j.ijpharm.2014.02.047

1873-3476

Emanuela Fabiola Craparo, Carla Sardo, Rosa Serio, Maria Grazia Zizzo, Maria Luisa Bondı̀, Gaetano Giammona, Gennara Cavallaro,

Hepatocellular Carcinoma Treatment and Prognosis

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.