title: Neuronal Uptake and Neuroprotective Properties of Curcumin-Loaded Nanoparticles on SK-N-SH Cell Line: Role of Poly(lactide-co-glycolide) Polymeric Matrix Composition.
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.
authors.affiliation: INRS-Institut Armand Frappier, 531 Boulevard des Prairies, Laval, Quebec H7V 1B7, Canada.|INAF, Laval University , Québec G1V 0A6, Canada.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Djiokeng Paka
authors.affiliation: INRS-Institut Armand Frappier, 531 Boulevard des Prairies, Laval, Quebec H7V 1B7, Canada.
authors.forename: Sihem
authors.initials: S
authors.lastname: Doggui
authors.affiliation: INRS-Institut Armand Frappier, 531 Boulevard des Prairies, Laval, Quebec H7V 1B7, Canada.
authors.forename: Ahlem
authors.initials: A
authors.lastname: Zaghmi
authors.affiliation: Faculté de Pharmacie, EA3452 CITHEFOR, Université de Lorraine , 54000 Nancy, France.
authors.forename: Ramia
authors.initials: R
authors.lastname: Safar
authors.affiliation: INRS-EMT, Québec H5A 1K6, Canada.
authors.forename: Lé
authors.initials: L
authors.lastname: Dao
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg , 67081 Strasbourg, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reisch
authors.affiliation: Laboratoire de Biophotonique et Pharmacologie, Faculté de Pharmacie, Université de Strasbourg , 67081 Strasbourg, France.
authors.forename: Andrey
authors.initials: A
authors.lastname: Klymchenko
authors.affiliation: Laboratoire de Nanotechnologies Pharmaceutiques, Faculté de Pharmacie, Université de Montréal , Montréal H3T 1J4, Canada.
authors.forename: V Gaëlle
authors.initials: VG
authors.lastname: Roullin
authors.affiliation: Faculté de Pharmacie, EA3452 CITHEFOR, Université de Lorraine , 54000 Nancy, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Joubert
authors.affiliation: INRS-Institut Armand Frappier, 531 Boulevard des Prairies, Laval, Quebec H7V 1B7, Canada.|INAF, Laval University , Québec G1V 0A6, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Ramassamy
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011098:Polyglactin 910 / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D011108:Polymers; D017382:Reactive Oxygen Species; D011098:Polyglactin 910; D003474:Curcumin
keywords: curcumin; nanoformulation; neuroprotective genes; oxidative stress; tau hyperphosphorylation