PEGylated hyaluronic acid-coated liposome for enhanced in vivo efficacy of sorafenib via active tumor cell targeting and prolonged systemic exposure

被引：68

作者：

Mo, Lingxuan ^{[1
]}

Song, Jae Geun ^{[1
]}

Lee, Hankyu ^{[1
]}

Zhao, Mengjia ^{[1
]}

Kim, Hyeon Young ^{[1
]}

Lee, Yoon Ji ^{[1
]}

Ko, Hyuk Wan ^{[1
]}

Han, Hyo-Kyung K ^{[1
]}

机构：

[1] Dongguk Univ Seoul, Coll Pharm, Goyang, South Korea

来源：

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE | 2018年 / 14卷 / 02期

基金：

新加坡国家研究基金会;

关键词：

Sorafenib; Tumor targeting; Hyaluronic acid; Liposome; Prolonged circulation; CATIONIC LIPOSOMES; DRUG-DELIVERY; RAF/MEK/ERK PATHWAY; GRAFTED LIPOSOMES; IMMUNE-RESPONSE; PHARMACOKINETICS; NANOPARTICLES; CIRCULATION; BIOAVAILABILITY; TRANSFECTION;

D O I：

10.1016/j.nano.2017.12.003

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

This study aimed to design an effective formulation for enhancing the tumor-targeted delivery of sorafenib. Three sorafenib-loaded liposomal formulations including uncoated liposome (SF-Lip), hyaluronic acid-coated liposome (HA-SF-Lip), and PEGylated hyaluronic acid-coated liposome (PEG-HA-SF-Lip) were developed with narrow size distribution and high encapsulation efficiency. The cellular uptake and cytotoxicity of HA-SF-Lip and PEG-HA-SF-Lip were greater than those of SF-Lip in MDA-MB-231 cells overexpressing CD44, whereas there were no significant differences in MCF-7 cells with low CD44 expression, indicating the CD44-mediated cellular uptake of coated liposomes. In comparison with sorafenib solution, PEG-HA-SF-Lip increased the systemic exposure and plasma half-life in rats by 3-fold and 2-fold, respectively. Consistently, PEG-HA-SF-Lip was the most effective for tumor growth inhibition through CD44 targeting in the MDA-MB-231 tumor xenograft mouse model. Taken together, the present study suggests that PEG-HA-SF-Lip might be effective for the tumor-targeted delivery of sorafenib with enhanced systemic exposure and longer blood circulation. (c) 2017 Elsevier Inc. All rights reserved.

引用

页码：557 / 567

页数：11

共 47 条

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