Evolution of availability of curcumin inside poly-lactic-co-glycolic acid nanoparticles: impact on antioxidant and antinitrosant properties

Abstract

Didier Betbeder,1–4 Emmanuelle Lipka,1,2,5 Mike Howsam,6 Rodolphe Carpentier1–3 1U995-LIRIC, Inserm (Institut National de la Recherche Médicale), Lille, France; 2U995-LIRIC, CHRU de Lille, Lille, France; 3U995-LIRIC, Faculté de Médecine, Université de Lille, Lille, France; 4Faculté des Sciences du Sport, Université d’Artois, Arras, France; 5Faculté de Pharmacie, Université de Lille, Lille, France; 6Faculté de Pharmacie, Université de Lille, Centre Universitaire de Mesures et d’Analyses, Lille, France Purpose: Curcumin exhibits antioxidant properties potentially beneficial for human health; however, its use in clinical applications is limited by its poor solubility and relative instability. Nanoparticles exhibit interesting features for the efficient distribution and delivery of curcumin into cells, and could also increase curcumin stability in biological systems. There is a paucity of information regarding the evolution of the antioxidant properties of nanoparticle-encapsulated curcumin.Method: We described a simple method of curcumin encapsulation in poly-lactic-co-glycolic acid (PLGA) nanoparticles without the use of detergent. We assessed, in epithelial cells and in an acellular model, the evolution of direct antioxidant and antinitrosant properties of free versus PLGA-encapsulated curcumin after storage under different conditions (light vs darkness, 4°C vs 25°C vs 37°C).Results: In epithelial cells, endocytosis and efflux pump inhibitors showed that the increased antioxidant activity of PLGA-encapsulated curcumin relied on bypassing the efflux pump system. Acellular assays showed that the antioxidant effect of curcumin was greater when loaded in PLGA nanoparticles. Furthermore, we observed that light decreased, though heat restored, antioxidant activity of PLGA-encapsulated curcumin, probably by modulating the accessibility of curcumin to reactive oxygen species, an observation supported by results from quenching experiments. Moreover, we demonstrated a direct antinitrosant activity of curcumin, enhanced by PLGA encapsulation, which was increased by light exposure.Conclusion: These results suggest that the antioxidant and antinitrosant activities of encapsulated curcumin are light sensitive and that nanoparticle modifications over time and with temperature may facilitate curcumin contact with reactive oxygen species. These results highlight the importance of understanding effects of nanoparticle maturation on an encapsulated drug’s activity. Keywords: PLGA nanoparticles, antioxidant, curcumin, evolution, maturation