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Neuronal Uptake and Neuroprotective Properties of Curcumin-Loaded Nanoparticles on SK-N-SH Cell Line: Role of Poly(lactide-co-glycolide) Polymeric Matrix Composition.
- Source :
-
Molecular pharmaceutics [Mol Pharm] 2016 Feb 01; Vol. 13 (2), pp. 391-403. Date of Electronic Publication: 2015 Dec 23. - Publication Year :
- 2016
-
Abstract
- Curcumin, a neuroprotective agent with promising therapeutic approach has poor brain bioavailability. Herein, we demonstrate that curcumin-encapsulated poly(lactide-co-glycolide) (PLGA) 50:50 nanoparticles (NPs-Cur 50:50) are able to prevent the phosphorylation of Akt and Tau proteins in SK-N-SH cells induced by H2O2 and display higher anti-inflammatory and antioxidant activities than free curcumin. PLGA can display various physicochemical and degradation characteristics for controlled drug release applications according to the matrix used. We demonstrate that the release of curcumin entrapped into a PLGA 50:50 matrix (NPs-Cur 50:50) is faster than into PLGA 65:35. We have studied the effects of the PLGA matrix on the expression of some key antioxidant- and neuroprotective-related genes such as APOE, APOJ, TRX, GLRX, and REST. NPs-Cur induced the elevation of GLRX and TRX while decreasing APOJ mRNA levels and had no effect on APOE and REST expressions. In the presence of H2O2, both NPs-Cur matrices are more efficient than free curcumin to prevent the induction of these genes. Higher uptake was found with NPs-Cur 50:50 than NPs-Cur 65:35 or free curcumin. By using PLGA nanoparticles loaded with the fluorescent dye Lumogen Red, we demonstrated that PLGA nanoparticles are indeed taken up by neuronal cells. These data highlight the importance of polymer composition in the therapeutic properties of the nanodrug delivery systems. Our study demonstrated that NPs-Cur enhance the action of curcumin on several pathways implicated in the pathophysiology of Alzheimer's disease (AD). Overall, these results suggest that PLGA nanoparticles are a promising strategy for the brain delivery of drugs for the treatment of AD.
- Subjects :
- Antineoplastic Agents pharmacology
Antioxidants pharmacology
Gene Expression Profiling
Humans
NF-E2-Related Factor 2 genetics
Nanoparticles chemistry
Neuroblastoma metabolism
Neuroblastoma pathology
Neurons cytology
Neurons metabolism
Oxidative Stress drug effects
Reactive Oxygen Species metabolism
Real-Time Polymerase Chain Reaction
Tumor Cells, Cultured
Curcumin pharmacology
Nanoparticles administration & dosage
Neuroblastoma drug therapy
Neurons drug effects
Neuroprotective Agents pharmacology
Polyglactin 910 chemistry
Polymers chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1543-8392
- Volume :
- 13
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular pharmaceutics
- Publication Type :
- Academic Journal
- Accession number :
- 26618861
- Full Text :
- https://doi.org/10.1021/acs.molpharmaceut.5b00611