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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

Mechanism of potentiation of antioxidant activity by PLGA-NP.Notes: A549 cells were treated with endocytosis pathway (Fil, Nys, PAO, Chl) or efflux pump (Ela) inhibitors then loaded with free curcumin (A) or PLGA/DiD-NP (B). The fluorescence was analyzed by cytometry and results are expressed as mean fluorescence intensity ± SEM.Abbreviations: PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; DiD, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt; SEM, standard error of the mean; Fil, filipin III; Nys, nystatin; PAO, phenylarsine oxide; Chl, chlorpromazine; Ela, elacridar.
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f2-ijn-10-5355: Mechanism of potentiation of antioxidant activity by PLGA-NP.Notes: A549 cells were treated with endocytosis pathway (Fil, Nys, PAO, Chl) or efflux pump (Ela) inhibitors then loaded with free curcumin (A) or PLGA/DiD-NP (B). The fluorescence was analyzed by cytometry and results are expressed as mean fluorescence intensity ± SEM.Abbreviations: PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; DiD, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt; SEM, standard error of the mean; Fil, filipin III; Nys, nystatin; PAO, phenylarsine oxide; Chl, chlorpromazine; Ela, elacridar.

Mentions: For free curcumin, a slight increase in uptake by cells was observed using caveolae (filipin III and nystatin) and clathrin pathway inhibitors (phenylarsine oxide and chlorpromazine). However, a greater increase was shown with elacridar (Figure 2A), an inhibitor of the efflux pump system that targets P-gp/ABCG1 and BCRP/ABCG2. This suggested that free curcumin diffuses through the plasma membrane but is excluded from cells by the multidrug resistance system.


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)

Mechanism of potentiation of antioxidant activity by PLGA-NP.Notes: A549 cells were treated with endocytosis pathway (Fil, Nys, PAO, Chl) or efflux pump (Ela) inhibitors then loaded with free curcumin (A) or PLGA/DiD-NP (B). The fluorescence was analyzed by cytometry and results are expressed as mean fluorescence intensity ± SEM.Abbreviations: PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; DiD, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt; SEM, standard error of the mean; Fil, filipin III; Nys, nystatin; PAO, phenylarsine oxide; Chl, chlorpromazine; Ela, elacridar.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-10-5355: Mechanism of potentiation of antioxidant activity by PLGA-NP.Notes: A549 cells were treated with endocytosis pathway (Fil, Nys, PAO, Chl) or efflux pump (Ela) inhibitors then loaded with free curcumin (A) or PLGA/DiD-NP (B). The fluorescence was analyzed by cytometry and results are expressed as mean fluorescence intensity ± SEM.Abbreviations: PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; DiD, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine, 4-chlorobenzenesulfonate salt; SEM, standard error of the mean; Fil, filipin III; Nys, nystatin; PAO, phenylarsine oxide; Chl, chlorpromazine; Ela, elacridar.
Mentions: For free curcumin, a slight increase in uptake by cells was observed using caveolae (filipin III and nystatin) and clathrin pathway inhibitors (phenylarsine oxide and chlorpromazine). However, a greater increase was shown with elacridar (Figure 2A), an inhibitor of the efflux pump system that targets P-gp/ABCG1 and BCRP/ABCG2. This suggested that free curcumin diffuses through the plasma membrane but is excluded from cells by the multidrug resistance system.

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