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Int. J. Mol. Sci. 2013, 14(2), 2862-2874; doi:10.3390/ijms14022862

In Vitro and in Vivo Evaluation of Lactoferrin-Conjugated Liposomes as a Novel Carrier to Improve the Brain Delivery

Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Institute of Nuclear Energy Research, Longtan 32546, Taiwan
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 19 November 2012 / Revised: 4 January 2013 / Accepted: 22 January 2013 / Published: 29 January 2013
(This article belongs to the Special Issue Bioactive Nanoparticles 2012)
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In this study, lactoferrin-conjugated PEGylated liposomes (PL), a potential drug carrier for brain delivery, was loaded with radioisotope complex, 99mTc labeled N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (99mTc-BMEDA) for in vitro and in vivo evaluations. The hydrophilicity of liposomes was enhanced by PEGylation which was not an ideal brain delivery system for crossing the blood brain barrier (BBB). With the modification of a brain-targeting ligand, lactoferrin (Lf), the PEGylated liposome (PL) might become a potential brain delivery vehicle. In order to test the hypothesis in vitro and in vivo, 99mTc-BMEDA was loaded into the liposomes as a reporter with or without Lf-conjugation. The mouse brain endothelia cell line, bEnd.3 cells, was cultured to investigate the potential uptake of liposomes in vitro. The in vivo uptake by the mouse brain of the liposomes was detected by tissue biodistribution study. The results indicated that Lf-conjugated PEGylated liposome showed more than three times better uptake efficiency in vitro and two-fold higher of brain uptake in vivo than PEGlyated liposome. With the success of loading the potential Single Photon Emission Tomography (SPECT) imaging probe, 99mTc-BMEDA, Lf-PL might serve as a promising brain delivery system for loading diagnostics or therapeutics of various brain disorders.
Keywords: lactoferrin; PEGylated liposome; blood-brain barrier; 99mTc lactoferrin; PEGylated liposome; blood-brain barrier; 99mTc
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Huang, F.-Y.J.; Chen, W.-J.; Lee, W.-Y.; Lo, S.-T.; Lee, T.-W.; Lo, J.-M. In Vitro and in Vivo Evaluation of Lactoferrin-Conjugated Liposomes as a Novel Carrier to Improve the Brain Delivery. Int. J. Mol. Sci. 2013, 14, 2862-2874.

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