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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

Light and heat effects on Cur-NP antioxidant and antinitrosant activities.Notes: Antioxidant (A, B) and antinitrosant (C, D) activities of free (A, C) or NP-formulated (B, D) curcumin were analyzed in vitro. Free or NP-formulated curcumin were stored in various conditions of light and temperature (darkness: 4°C, 25°C, 37°C; light: 25°C exposed to light) for 0 (D0), 1 (D1), or 2 (D2) days. An extra-day at 37°C (D2+) was included for some conditions to study PLGA-NP maturation and its effect on curcumin release and availability. (A) Light exposure of free curcumin decreased its antioxidant activity. ***P<0.005 versus D1 light. (B) Light exposure of NP-formulated curcumin decreased its antioxidant activity, but this was restored by a 1-day incubation at 37°C. ***P<0.005 versus D0, D1, and other D2. (C) Light exposure of free curcumin increased its antinitrosant activity. ***P<0.005 versus other D2. (D) Incubation at 25°C of NP-formulated curcumin decreased its antinitrosant activity; this was not restored by a 1-day incubation at 37°C. Light exposure exacerbated the decrease in antinitrosant activity of NP-formulated curcumin. ***P<0.005 versus D0 and other D2. Results are expressed in mean ± SEM.Abbreviations: Cur-NP, curcumin-loaded PLGA-based nanoparticles; F, free curcumin; PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; SEM, standard error of the mean; ROS, reactive oxygen species; RNS, reactive nitrogen species.
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f4-ijn-10-5355: Light and heat effects on Cur-NP antioxidant and antinitrosant activities.Notes: Antioxidant (A, B) and antinitrosant (C, D) activities of free (A, C) or NP-formulated (B, D) curcumin were analyzed in vitro. Free or NP-formulated curcumin were stored in various conditions of light and temperature (darkness: 4°C, 25°C, 37°C; light: 25°C exposed to light) for 0 (D0), 1 (D1), or 2 (D2) days. An extra-day at 37°C (D2+) was included for some conditions to study PLGA-NP maturation and its effect on curcumin release and availability. (A) Light exposure of free curcumin decreased its antioxidant activity. ***P<0.005 versus D1 light. (B) Light exposure of NP-formulated curcumin decreased its antioxidant activity, but this was restored by a 1-day incubation at 37°C. ***P<0.005 versus D0, D1, and other D2. (C) Light exposure of free curcumin increased its antinitrosant activity. ***P<0.005 versus other D2. (D) Incubation at 25°C of NP-formulated curcumin decreased its antinitrosant activity; this was not restored by a 1-day incubation at 37°C. Light exposure exacerbated the decrease in antinitrosant activity of NP-formulated curcumin. ***P<0.005 versus D0 and other D2. Results are expressed in mean ± SEM.Abbreviations: Cur-NP, curcumin-loaded PLGA-based nanoparticles; F, free curcumin; PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; SEM, standard error of the mean; ROS, reactive oxygen species; RNS, reactive nitrogen species.

Mentions: The stability of free or Cur-NP antioxidant activity was then studied in the acellular system described earlier. Free curcumin was stored for 2 days in the dark at 4°C, 37°C, or 25°C, and under natural light at 25°C. The antioxidant effect of free curcumin reduced the amount of ROS by about 50% compared with the control. This antioxidant activity did not change over time or as a function of storage temperature. However, an increased in ROS was observed when curcumin was stored for 2 days under conditions of natural light, meaning that curcumin lost some of its antioxidant activity under these storage conditions (Figure 4A). Cur-NP was also examined under the same conditions. Compared with D0, which had an antioxidant effect of over 80%, no difference was observed when Cur-NP formulations were stored in the dark for 2 days at 4°C, 37°C, or 25°C. Nonetheless, as for free curcumin, more ROS were observed with Cur-NP stored at 25°C under light for 2 days, meaning that the antioxidant properties of Cur-NP had decreased. All Cur-NP (except those initially stored at 37°C) were then kept for an additional day in the dark at 37°C (D2+), to determine whether temperature modulates PLGA porosity and degradation, and hence curcumin accessibility. No difference was observed for 4°C or 25°C (darkness) conditions; however, formulations first exposed to light and then 37°C demonstrated renewed antioxidant activity (Figure 4B). These data suggest that the antioxidant activity of Cur-NP that had been reduced by light exposure could be subsequently restored by exposure to moderate heat (37°C).


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)

Light and heat effects on Cur-NP antioxidant and antinitrosant activities.Notes: Antioxidant (A, B) and antinitrosant (C, D) activities of free (A, C) or NP-formulated (B, D) curcumin were analyzed in vitro. Free or NP-formulated curcumin were stored in various conditions of light and temperature (darkness: 4°C, 25°C, 37°C; light: 25°C exposed to light) for 0 (D0), 1 (D1), or 2 (D2) days. An extra-day at 37°C (D2+) was included for some conditions to study PLGA-NP maturation and its effect on curcumin release and availability. (A) Light exposure of free curcumin decreased its antioxidant activity. ***P<0.005 versus D1 light. (B) Light exposure of NP-formulated curcumin decreased its antioxidant activity, but this was restored by a 1-day incubation at 37°C. ***P<0.005 versus D0, D1, and other D2. (C) Light exposure of free curcumin increased its antinitrosant activity. ***P<0.005 versus other D2. (D) Incubation at 25°C of NP-formulated curcumin decreased its antinitrosant activity; this was not restored by a 1-day incubation at 37°C. Light exposure exacerbated the decrease in antinitrosant activity of NP-formulated curcumin. ***P<0.005 versus D0 and other D2. Results are expressed in mean ± SEM.Abbreviations: Cur-NP, curcumin-loaded PLGA-based nanoparticles; F, free curcumin; PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; SEM, standard error of the mean; ROS, reactive oxygen species; RNS, reactive nitrogen species.
© Copyright Policy
Related In: Results  -  Collection

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

f4-ijn-10-5355: Light and heat effects on Cur-NP antioxidant and antinitrosant activities.Notes: Antioxidant (A, B) and antinitrosant (C, D) activities of free (A, C) or NP-formulated (B, D) curcumin were analyzed in vitro. Free or NP-formulated curcumin were stored in various conditions of light and temperature (darkness: 4°C, 25°C, 37°C; light: 25°C exposed to light) for 0 (D0), 1 (D1), or 2 (D2) days. An extra-day at 37°C (D2+) was included for some conditions to study PLGA-NP maturation and its effect on curcumin release and availability. (A) Light exposure of free curcumin decreased its antioxidant activity. ***P<0.005 versus D1 light. (B) Light exposure of NP-formulated curcumin decreased its antioxidant activity, but this was restored by a 1-day incubation at 37°C. ***P<0.005 versus D0, D1, and other D2. (C) Light exposure of free curcumin increased its antinitrosant activity. ***P<0.005 versus other D2. (D) Incubation at 25°C of NP-formulated curcumin decreased its antinitrosant activity; this was not restored by a 1-day incubation at 37°C. Light exposure exacerbated the decrease in antinitrosant activity of NP-formulated curcumin. ***P<0.005 versus D0 and other D2. Results are expressed in mean ± SEM.Abbreviations: Cur-NP, curcumin-loaded PLGA-based nanoparticles; F, free curcumin; PLGA, poly-lactic-co-glycolic acid; NP, nanoparticles; SEM, standard error of the mean; ROS, reactive oxygen species; RNS, reactive nitrogen species.
Mentions: The stability of free or Cur-NP antioxidant activity was then studied in the acellular system described earlier. Free curcumin was stored for 2 days in the dark at 4°C, 37°C, or 25°C, and under natural light at 25°C. The antioxidant effect of free curcumin reduced the amount of ROS by about 50% compared with the control. This antioxidant activity did not change over time or as a function of storage temperature. However, an increased in ROS was observed when curcumin was stored for 2 days under conditions of natural light, meaning that curcumin lost some of its antioxidant activity under these storage conditions (Figure 4A). Cur-NP was also examined under the same conditions. Compared with D0, which had an antioxidant effect of over 80%, no difference was observed when Cur-NP formulations were stored in the dark for 2 days at 4°C, 37°C, or 25°C. Nonetheless, as for free curcumin, more ROS were observed with Cur-NP stored at 25°C under light for 2 days, meaning that the antioxidant properties of Cur-NP had decreased. All Cur-NP (except those initially stored at 37°C) were then kept for an additional day in the dark at 37°C (D2+), to determine whether temperature modulates PLGA porosity and degradation, and hence curcumin accessibility. No difference was observed for 4°C or 25°C (darkness) conditions; however, formulations first exposed to light and then 37°C demonstrated renewed antioxidant activity (Figure 4B). These data suggest that the antioxidant activity of Cur-NP that had been reduced by light exposure could be subsequently restored by exposure to moderate heat (37°C).

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