文献类型：期刊文献

英文题名：A novel lactoferrin-modified β-cyclodextrin nanocarrier for brain-targeting drug delivery

作者：Ye, Yajing[2];Sun, Yi[2];Zhao, Hongli[3];Lan, Minbo[3];Gao, Feng[1,2,3];Song, Chao[1];Lou, Kaiyan[1];Li, Hao[1];Wang, Wei[1,4]

机构：[1]E China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]E China Univ Sci & Technol, Dept Pharmaceut, Sch Pharm, Shanghai 200237, Peoples R China;[3]E China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[4]Univ New Mexico, Dept Chem & Chem Biol, Albuquerque, NM 87131 USA

年份：2013

卷号：458

期号：1

起止页码：110

外文期刊名：INTERNATIONAL JOURNAL OF PHARMACEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000326983000015)】；

基金：The authors acknowledge the financial support from the Fundamental Research Funds for the Central Universities (WY1213013 ECUST) and Shanghai Nanotechnology Leading Academic Discipline Foundation (No. 0852nm05900) and 111 Program of China (No. B07023). This work was also supported by Science and Technology Commission of Shanghai Municipality (STCSM, contract Nos. 11DZ2260600 and 10DZ2220500).

语种：英文

外文关键词：beta-cyclodextrin derivatives; Lactoferrin; Transferrin; Brain-targeting; Nano-drug delivery system

摘要：The blood-brain barrier (BBB) restricts the transfer and delivery of most drug substances to brain. In this study, a novel nano-drug delivery system for brain-targeting was developed and investigated in vitro and in vivo. Lactoferrin (Lf) was selected as a brain-targeting ligand and conjugated to beta-cyclodextrin (beta-CD) via the heterobifunctional polyethyleneglycol (PEG) linker NHS-PEG-MAL, yielding Lf conjugated beta-cyclodextrin (Lf-CD). UV-vis, FTIR, NMR and transmission electron microscopy (TEM) techniques clearly demonstrated the successful synthesis of Lf-CD nanoparticles with the average diameter of 92.9 +/- 16.5 nm. Using near-infrared fluorescent dye IR-775 chloride (IR) as a model compound of poorly water-soluble drugs, IR-loaded Lf-CD nanoparticles (Lf-CD/IR) were successfully prepared with a high entrapment efficiency of 98.1 +/- 4.8%. Biodistribution and pharmacokinetics of Lf-CD/IR were evaluated in KM mice after intravenous administration. The results of tissue distribution studies revealed that Lf-CD/IR treatment showed greatly improved BBB transport efficiency. In addition, AUC(0-2) h of IR in brain after Lf-CD/IR treatment was seven fold higher compared with that of IR treatment without Lf-CD nanocarriers, demonstrating that the introduction of Lf-CD drug-delivery system positively resulted in a higher AUC located in brain tissue. These results provide evidence that Lf-CD nanoparticles could be exploited as a potential brain-targeting drug delivery system for hydrophobic drugs and diagnostic reagents which normally fail to pass through the BBB. (C) 2013 Elsevier B.V. All rights reserved.