PEG-Stabilized Bilayer Nanodisks As Carriers for Doxorubicin Delivery

详细信息    查看全文

• 作者：Wenping Zhang ; Jin Sun ; Yan Liu ; Mengying Tao ; Xiaoyu Ai ; Xiaonan Su ; Cuifang Cai ; Yilin Tang ; Zhi Feng ; Xiaodan Yan ; Guoliang Chen ; Zhonggui He
• 刊名：Molecular Pharmaceutics
• 出版年：2014
• 出版时间：October 6, 2014
• 年：2014
• 卷：11
• 期：10
• 页码：3279-3290
• 全文大小：668K
• ISSN：1543-8392

文摘

Spherical nanoparticles as a classic delivery vehicle for anticancer drugs have been extensively investigated, but study on the shape of nanoparticles has received little attention until now. Here, a nonspherical poly(ethylene glycol) (PEG)-stabilized bilayer nanodisk consisting of 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC) and PEG5000-glyceryl distearate (PEG_5K-GCDS) was prepared for doxorubicin delivery, called DOX-Disks. The prepared disks were open bilayer structures, with a hydrophobic discoid center built by DSPC and a hydrophilic PEG edge. Mean particle diameter of the disk was 80.14 nm, and the disk height was about 6 nm with aspect ratio about 12. Encapsulation efficiency of DOX-Disks was as high as 96.1%, and DOX release from DOX-Disks was pH-dependent (25.6% of total DOX released at 24 h in pH 7.4). The pharmacokinetic performances showed that DOX-Disks demonstrated long circulation time in blood and larger AUC (11.7-fold of t_1/2 and 31.7-fold of AUC) in rats compared with DOX solutions (DOX-Sol). Tissue distribution in H22 tumor bearing mice demonstrated higher tumor accumulation (9.7-fold) and lower heart toxicities (25.7-fold) at 48 h after iv administration, in comparison with DOX-Sol. In addition, DOX-Disks exhibited much effectiveness in inhibiting tumor cell growth, and the IC₅₀ values were 2.03, 0.85, and 0.86 渭g/mL for DOX-Sol and 0.23, 0.24, and 0.20 渭g/mL for DOX-Disks after treatment for 48, 72, and 96 h against MCF-7/Adr cells, respectively. DOX-Disks were taken up into MCF-7/Adr cells via energy-dependent endocytosis processes, involved in clathrin-mediated, macropinocytosis-mediated, and non-clathrin- and non-caveolae-mediated endocytosis pathways. In summary, such PEG-stabilized bilayer nanodisks could be one of the promising carriers for antitumor drugs via extended blood circulation and improved tumor distribution.

Keywords:

drug delivery; bilayer nanodisks; doxorubicin; shape