A novel lactoferrin-modified β-cyclodextrin nanocarrier for brain-targeting drug delivery

Yajing Ye; Yi Sun; Hongli Zhao; Minbo Lan; Feng Gao; Chao Song; Kaiyan Lou; Hao Li; Wei Wang

doi:10.1016/j.ijpharm.2013.10.005

A novel lactoferrin-modified β-cyclodextrin nanocarrier for brain-targeting drug delivery

Yajing Ye, Yi Sun, Hongli Zhao, Minbo Lan, Feng Gao, Chao Song, Kaiyan Lou, Hao Li, Wei Wang

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

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, 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 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.

Original language	English (US)
Pages (from-to)	110-117
Number of pages	8
Journal	International Journal of Pharmaceutics
Volume	458
Issue number	1
DOIs	https://doi.org/10.1016/j.ijpharm.2013.10.005
State	Published - 2013
Externally published	Yes

Keywords

Brain-targeting
Lactoferrin
Nano-drug delivery system
Transferrin
beta;-cyclodextrin derivatives

ASJC Scopus subject areas

Pharmaceutical Science

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10.1016/j.ijpharm.2013.10.005

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@article{a1440b27cd3140cb9d55a93f9e7c5947,

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, AUC0-2 h 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.",

keywords = "Brain-targeting, Lactoferrin, Nano-drug delivery system, Transferrin, beta;-cyclodextrin derivatives",

author = "Yajing Ye and Yi Sun and Hongli Zhao and Minbo Lan and Feng Gao and Chao Song and Kaiyan Lou and Hao Li and Wei Wang",

note = "Funding Information: 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).",

year = "2013",

doi = "10.1016/j.ijpharm.2013.10.005",

language = "English (US)",

volume = "458",

pages = "110--117",

journal = "International Journal of Pharmaceutics",

issn = "0378-5173",

publisher = "Elsevier B.V.",

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TY - JOUR

T1 - A novel lactoferrin-modified β-cyclodextrin nanocarrier for brain-targeting drug delivery

AU - Ye, Yajing

AU - Sun, Yi

AU - Zhao, Hongli

AU - Lan, Minbo

AU - Gao, Feng

AU - Song, Chao

AU - Lou, Kaiyan

AU - Li, Hao

AU - Wang, Wei

N1 - Funding Information: 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).

PY - 2013

Y1 - 2013

N2 - 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, AUC0-2 h 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.

AB - 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, AUC0-2 h 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.

KW - Brain-targeting

KW - Lactoferrin

KW - Nano-drug delivery system

KW - Transferrin

KW - beta;-cyclodextrin derivatives

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A novel lactoferrin-modified β-cyclodextrin nanocarrier for brain-targeting drug delivery

Abstract

Keywords

ASJC Scopus subject areas

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