title: Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line.
abstract: Curcumin, a natural polyphenolic pigment present in the spice turmeric (Curcuma longa), is known to possess a pleiotropic activity such as antioxidant, anti-inflammatory, and anti-amyloid-β activities. However, these benefits of curcumin are limited by its poor aqueous solubility and oral bioavailability. In the present study, a polymer-based nanoparticle approach has been utilized to deliver drugs to neuronal cells. Curcumin was encapsulated in biodegradable poly (lactide-co-glycolide) (PLGA) based-nanoparticulate formulation (Nps-Cur). Dynamic laser light scattering and transmission electronic microscopy analysis indicated a particle diameter ranging from 80 to 120 nm. The entrapment efficiency was 31% with 15% drug-loading. In vitro release kinetics of curcumin from Nps-Cur revealed a biphasic pattern with an initial exponential phase followed by a slow release phase. Cellular internalization of Nps-Cur was confirmed by fluorescence and confocal microscopy with a wide distribution of the fluorescence in the cytoplasm and within the nucleus. The prepared nanoformulation was characterized for cellular toxicity and biological activity. Cytotoxicity assays showed that void PLGA-nanoparticles (Nps) and curcumin-loaded PLGA nanoparticles (Nps-Cur) were nontoxic to human neuroblastoma SK-N-SH cells. Moreover, Nps-Cur was able to protect SK-N-SH cells against H2O2 and prevent the elevation of reactive oxygen species and the consumption of glutathione induced by H2O2. Interestingly, Nps-Cur was also able to prevent the induction of the redox-sensitive transcription factor Nrf2 in the presence of H2O2. Taken together, these results suggest that Nps-Cur could be a promising drug delivery strategy to protect neurons against oxidative damage as observed in Alzheimer's disease.
authors.affiliation: INRS-Institut Armand-Frappier, Laval, QC, Canada INRS-EMT, QC, Canada.
authors.forename: Sihem
authors.initials: S
authors.lastname: Doggui
authors.forename: Jasjeet Kaur
authors.initials: JK
authors.lastname: Sahni
authors.forename: Madeleine
authors.initials: M
authors.lastname: Arseneault
authors.forename: Lé
authors.initials: L
authors.lastname: Dao
authors.forename: Charles
authors.initials: C
authors.lastname: Ramassamy
mesh_terms: D000975:Antioxidants / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D003474:Curcumin / Q000493:pharmacokinetics*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000493:pharmacokinetics*; D046529:Microscopy, Electron, Transmission; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D053758:Nanoparticles / Q000627:therapeutic use* / Q000648:ultrastructure; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000493:pharmacokinetics*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011100:Polyglycolic Acid / Q000493:pharmacokinetics*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005978:Glutathione; D003474:Curcumin