Galactosylated polymeric carriers for liver targeting of sorafenib
Galactosylated polymeric carriers for liver targeting of sorafenib
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DOI：
10.1016/j.ijpharm.2014.02.047
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发表时间：
2014-05-15
影响因子：
5.8
通讯作者：
Cavallaro, Gennara
中科院分区：
文献类型：
--
作者：
Craparo, Emanuela F.;Sardo, Carla;Cavallaro, Gennara
在本文中，我们描述了利用碳水化合物受体 ASGPR 的存在，制备可能能够将索拉非尼携带到肝细胞以治疗肝癌 (HCC) 的肝脏靶向聚合物胶束。这些胶束是从半乳糖基化的聚丙交酯-聚氨基酸缀合物开始制备的。后者是通过 α,β-聚（N-2-羟乙基）（2-氨基乙基氨基甲酸酯）-D,L-天冬酰胺（PHEA-EDA）与聚乳酸（PLA）发生化学反应，然后与乳糖反应，得到 PHEA-EDA-PLA-GAL 共聚物而获得的。在水性介质中以低 PHEA-EDA-PLA-GAL 共聚物浓度值获得具有纳米尺寸和略正 zeta 电位的肝脏靶向负载索拉非尼胶束。对小鼠的生物分布研究表明，口服负载索拉非尼的 PHEA-EDA-PLA-GAL 胶束后，索拉非尼优先积聚到肝脏中。这一发现为未来针对肝脏治疗 HCC 的负载索拉非尼胶束的药物递送策略带来了希望。 (C) 2014 Elsevier B.V. 保留所有权利。
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.