A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease.
In this study, a novel low density lipoprotein (LDL)-mimic nanostructured lipid carrier (NLC) modified with lactoferrin (Lf) and loaded with curcumin (Cur) was designed for brain-targeted delivery, and its effect on controlling the progression of Alzheimer's disease (AD) in rats was evaluated. NLC with the composition resembling the lipid portion of LDL was prepared by using solvent evaporation method. Lf was adsorbed onto the surface of NLC via electrostatic interaction to yield Lf modified-NLC (Lf-mNLC) as the LDL-mimic nanocarrier. In order to make sure more Lf was adsorbed on the surface of NLC, negatively charged carboxylated polyethylene glycol (100) monostearate (S100-COOH) was synthesized and anchored into NLC. Different levels of S100-COOH (0-0.02 mmol) and Lf modified NLC (0.5-2.5 mg/mL of Lf solution) were prepared and characterized. The uptake and potential cytotoxicities of different preparations were investigated in the brain capillary endothelial cells (BCECs). An AD model of rats was employed to evaluate the therapeutic effects of Lf-mNLC. The results indicate that Lf-mNLC with a high level of Lf showed the maximum uptake in BCECs (1.39 folds greater than NLC) as cellular uptake of Lf-mNLC by BCECs was found to be mediated by the Lf receptor. FRET studies showed Cur still wrapped inside NLC after uptake by BCECs, demonstrating stability of the carrier as it moved across the BBB. Ex vivo imaging studies exposed Lf-mNLC could effectively permeate BBB and preferentially accumulate in the brain (2.78 times greater than NLC). Histopathological evaluation confirmed superior efficacy of Lf-mNLC in controlling the damage associated with AD. In conclusion, Lf-mNLC is a promising drug delivery system for targeting therapy of brain disease.
['Meng|Fanfei|F|', 'Asghar|Sajid|S|', 'Gao|Shiya|S|', 'Su|Zhigui|Z|', 'Song|Jue|J|', 'Huo|Meirong|M|', 'Meng|Weidong|W|', 'Ping|Qineng|Q|', 'Xiao|Yanyu|Y|']
D000544:Alzheimer Disease D000818:Animals D002478:Cells, Cultured D003474:Curcumin D004337:Drug Carriers D016503:Drug Delivery Systems D008077:Lipoproteins, LDL D008315:Malondialdehyde D051379:Mice D008813:Mice, Inbred ICR D018716:Molecular Mimicry D053758:Nanoparticles D051381:Rats D017207:Rats, Sprague-Dawley D013050:Spectrometry, Fluorescence D013056:Spectrophotometry, Ultraviolet D014018:Tissue Distribution
Alzheimer's disease Lactoferrin Carboxylated polyethylene glycol (100) monostearate Brain targeting LDL-mimic nanostructured lipid carrier system