title: PEG-stabilized bilayer nanodisks as carriers for doxorubicin delivery.
abstract: 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 (PEG5K-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 t1/2 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 μg/mL for DOX-Sol and 0.23, 0.24, and 0.20 μg/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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , No. 103 Wenhua Road, Shenyang 110016, P. R. China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Zhang
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Mengying
authors.initials: M
authors.lastname: Tao
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Ai
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Su
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.forename: Yilin
authors.initials: Y
authors.lastname: Tang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Feng
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Yan
authors.forename: Guoliang
authors.initials: G
authors.lastname: Chen
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: bilayer nanodisks; doxorubicin; drug delivery; shape