title: A novel lactoferrin-modified β-cyclodextrin nanocarrier for brain-targeting drug delivery.
abstract: 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 β-cyclodextrin (β-CD) via the heterobifunctional polyethyleneglycol (PEG) linker NHS-PEG-MAL, yielding Lf conjugated β-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, AUC0-2h of IR in brain after Lf-CD/IR treatment was seven fold higher compared with that of IR treatment without Lf-CD nano-carriers, 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Ye
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhao
authors.forename: Minbo
authors.initials: M
authors.lastname: Lan
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Chao
authors.initials: C
authors.lastname: Song
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Lou
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D007781:Lactoferrin / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D016716:PC12 Cells; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D014018:Tissue Distribution; D047392:beta-Cyclodextrins / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D047392:beta-Cyclodextrins; D011092:Polyethylene Glycols; D007781:Lactoferrin
keywords: Brain-targeting; Lactoferrin; Nano-drug delivery system; Transferrin; β-cyclodextrin derivatives