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PLGA matrix - composition affects the therapeutic properties of nanocurcumin: Potential application in Alzheimer’s disease

Djioken Paka, Ghislain; Zaghmi, Ahlem; Ramassamy, Charles . PLGA matrix - composition affects the therapeutic properties of nanocurcumin: Potential application in Alzheimer’s disease In: 12ême colloque du centre de recherche Biomed, 5 mai 2016, Centre de congrès Palace, Laval (Québec).

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Résumé

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 apolipoprotein E (APOE), apolipoprotein J (APOJ), thioredoxin (TRX), glutaredoxin (GLRX), and the repressor element - 1 silencing transcription factor (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. By using PLGA nanoparticles loaded with the fluorescent 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. Moreover, our study demonstrated that NPs - Cur enhance the action of curcumin on several pathways implicated in the pathophysiology of AD. Overall, these results suggest that PLGA nanoparticles are a promising strategy for the brain delivery of drugs for the treatment of AD.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Présentation par affiche
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 25 déc. 2017 22:26
Dernière modification: 25 déc. 2017 22:26
URI: http://espace.inrs.ca/id/eprint/6619

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