期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 458, 期 1, 页码 110-117出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2013.10.005
关键词
beta-cyclodextrin derivatives; Lactoferrin; Transferrin; Brain-targeting; Nano-drug delivery system
资金
- Fundamental Research Funds for the Central Universities [WY1213013 ECUST]
- Shanghai Nanotechnology Leading Academic Discipline Foundation [0852nm05900]
- 111 Program of China [B07023]
- Science and Technology Commission of Shanghai Municipality (STCSM) [11DZ2260600, 10DZ2220500]
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.
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