A novel LDL-mimic nanocarrier for the targeted delivery of curcumin into the brain to treat Alzheimer's disease
Abstract
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.
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Curcumin-loaded lactoferrin-functionalized nanolipid carriers enhanced brain uptake by 2.78-fold and could recover hippocampal damage in AD animal model.
“In another study, curcumin-loaded lactoferrin-functionalized nanolipid carriers enhanced brain uptake by 2.78-fold and could recover hippocampal damage in the AD animal model.112”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [112]
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- Authors
- Meng, F., Asghar, S., Gao, S., Su, Z., Song, J., Huo, M., Meng, W., Ping, Q., & Xiao, Y.
- Affiliations
- China Pharmaceutical University (CN)
- Liaocheng People's Hospital (CN)
- Corresponding author
- Xiao, Yanyu
- Venue
- Colloids and Surfaces B: Biointerfaces
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 134
- Pages
- 88-97
- ISSN
- 0927-7765 (ISSN-L)
- OpenAlex
- W896498680
- Cited by
- 176
- References
- 49
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 16 · 2023: 21 · 2022: 23 · 2021: 20 · 2020: 22 · 2019: 16 · 2018: 16 · 2017: 12 · 2016: 10 · 2015: 1
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Colloids and Surfaces B Biointerfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Jiangsu Province (BK20130655, BK2012761)
- Open Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (SKLNMKF201204)
- College Students Innovation Project for the R&D of Novel Drugs (J1030830)
- National College Students’ Innovation Entrepreneurial Training Program (G13076)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Curcumin's Biomedical Applications
- Keywords
- nanostructured lipid carriers, curcumin, lactoferrin, Alzheimer's disease, brain drug delivery, blood-brain barrier permeability, brain microvascular endothelial cells, drug delivery systems
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Curcumin, Drug Carriers, Lipoproteins, LDL, Malondialdehyde, Mice, Inbred ICR, Spectrometry, Fluorescence, Spectrophotometry, Ultraviolet, Tissue Distribution, Drug Delivery Systems, Rats, Sprague-Dawley, Molecular Mimicry, Mice, Rats, Nanoparticles
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