期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 466, 期 1-2, 页码 172-180出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2014.02.047
关键词
Galactosylation; Polymeric micelles; Hepatic cell-targeted carriers; Active targeting
资金
- P.O.R. Sicilia, Misura 3.15 Quota Regionale
- MIUR [20109PLMH2]
- University of Palermo
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 alpha,beta-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. (C) 2014 Elsevier B. V. All rights reserved.
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