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

Betbeder D, Lipka E, Howsam M, Carpentier R - Int J Nanomedicine (2015)

Bottom Line: 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.These results highlight the importance of understanding effects of nanoparticle maturation on an encapsulated drug's activity.

View Article: PubMed Central - PubMed

Affiliation: U995-LIRIC, Inserm (Institut National de la Recherche Médicale), Lille, France ; U995-LIRIC, CHRU de Lille, Lille, France ; U995-LIRIC, Faculté de Médecine, Université de Lille, Lille, France ; Faculté des Sciences du Sport, Université d'Artois, Arras, France.

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.

No MeSH data available.


Related in: MedlinePlus

Development of an in vitro acellular method for measuring the antioxidant activity of Cur-NP.Notes: The oxidation probe H2DCF-DA and the ROS donor THBP were put into an empty 96-well plate. Then free or formulated curcumin (2 µM) was added and fluorescence of the probe was followed for 60 minutes. The Cur-NP was more antioxidant than free curcumin. Results are expressed in mean ± SEM.Abbreviations: H2DCF-DA, 2′,7′-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; THBP, tert-butyl hydroperoxide; PLGA, poly-lactic-co-glycolic acid; Cur-NP, curcumin-loaded PLGA-based nanoparticles; SEM, standard error of the mean; NP, nanoparticles.
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f3-ijn-10-5355: Development of an in vitro acellular method for measuring the antioxidant activity of Cur-NP.Notes: The oxidation probe H2DCF-DA and the ROS donor THBP were put into an empty 96-well plate. Then free or formulated curcumin (2 µM) was added and fluorescence of the probe was followed for 60 minutes. The Cur-NP was more antioxidant than free curcumin. Results are expressed in mean ± SEM.Abbreviations: H2DCF-DA, 2′,7′-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; THBP, tert-butyl hydroperoxide; PLGA, poly-lactic-co-glycolic acid; Cur-NP, curcumin-loaded PLGA-based nanoparticles; SEM, standard error of the mean; NP, nanoparticles.

Mentions: An in vitro, acellular system was developed to analyze the antioxidant activity of Cur-NP under conditions where no delay in endocytosis or degradation of the NP could occur. Free or Cur-NP was directly added to a ROS inducer (TBHP) with a ROS detector probe (H2DCF-DA). In the absence of curcumin, a progressive increase in ROS was detected and attained a 6.5-fold induction after 1 hour, while addition of free curcumin reduced this to a maximum threefold induction; Cur-NP was even more efficient than free curcumin and completely prevented ROS induction (Figure 3). This showed that curcumin encapsulated in NP has stronger antioxidant activity compared with free curcumin, even in the acellular system. This system further enabled us to follow the evolution of the antioxidant properties of PLGA-encapsulated curcumin when the formulations were exposed to light or heat.


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

Betbeder D, Lipka E, Howsam M, Carpentier R - Int J Nanomedicine (2015)

Development of an in vitro acellular method for measuring the antioxidant activity of Cur-NP.Notes: The oxidation probe H2DCF-DA and the ROS donor THBP were put into an empty 96-well plate. Then free or formulated curcumin (2 µM) was added and fluorescence of the probe was followed for 60 minutes. The Cur-NP was more antioxidant than free curcumin. Results are expressed in mean ± SEM.Abbreviations: H2DCF-DA, 2′,7′-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; THBP, tert-butyl hydroperoxide; PLGA, poly-lactic-co-glycolic acid; Cur-NP, curcumin-loaded PLGA-based nanoparticles; SEM, standard error of the mean; NP, nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554401&req=5

f3-ijn-10-5355: Development of an in vitro acellular method for measuring the antioxidant activity of Cur-NP.Notes: The oxidation probe H2DCF-DA and the ROS donor THBP were put into an empty 96-well plate. Then free or formulated curcumin (2 µM) was added and fluorescence of the probe was followed for 60 minutes. The Cur-NP was more antioxidant than free curcumin. Results are expressed in mean ± SEM.Abbreviations: H2DCF-DA, 2′,7′-dichlorodihydrofluorescein diacetate; ROS, reactive oxygen species; THBP, tert-butyl hydroperoxide; PLGA, poly-lactic-co-glycolic acid; Cur-NP, curcumin-loaded PLGA-based nanoparticles; SEM, standard error of the mean; NP, nanoparticles.
Mentions: An in vitro, acellular system was developed to analyze the antioxidant activity of Cur-NP under conditions where no delay in endocytosis or degradation of the NP could occur. Free or Cur-NP was directly added to a ROS inducer (TBHP) with a ROS detector probe (H2DCF-DA). In the absence of curcumin, a progressive increase in ROS was detected and attained a 6.5-fold induction after 1 hour, while addition of free curcumin reduced this to a maximum threefold induction; Cur-NP was even more efficient than free curcumin and completely prevented ROS induction (Figure 3). This showed that curcumin encapsulated in NP has stronger antioxidant activity compared with free curcumin, even in the acellular system. This system further enabled us to follow the evolution of the antioxidant properties of PLGA-encapsulated curcumin when the formulations were exposed to light or heat.

Bottom Line: 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.These results highlight the importance of understanding effects of nanoparticle maturation on an encapsulated drug's activity.

View Article: PubMed Central - PubMed

Affiliation: U995-LIRIC, Inserm (Institut National de la Recherche Médicale), Lille, France ; U995-LIRIC, CHRU de Lille, Lille, France ; U995-LIRIC, Faculté de Médecine, Université de Lille, Lille, France ; Faculté des Sciences du Sport, Université d'Artois, Arras, France.

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.

No MeSH data available.


Related in: MedlinePlus