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

Abstract

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

Supplementary materials

Figure S1 PLGA-NP do not interfere with ROS induction.

Notes: (A) A549 cells were loaded with H2DCF-DA and treated with PLGA nanoparticles (150 µg/cm²). Fluorescence of H2DCF-DA was measured to quantify ROS induction. Positive control was pyocyanin. Cells without H2DCF-DA served as specificity test for fluorescence. (B) A549 cells loaded with H2DCF-DA and treated with THBP, a ROS donor, with or without PLGA-NP (30 or 150 µg/cm²). Fluorescence of H2DCF-DA was measured to quantify ROS induction.

Abbreviations: PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; H2DCF-DA, 2′,7′-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; THBP, tert-butyl hydroperoxide.

Acknowledgments

The authors would like to thank the DigestScience Foundation for their support.

Author contributions

The manuscript was written through contributions of all the authors. All the authors have given approval to the final version of the manuscript. The design and conception of experiments were contributed by RC and DB. Interpretation of data was done by RC and DB. Acquisition of data was performed by RC and EL. All authors contributed toward data analysis, drafting and critically revising the paper, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.