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Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions.

Sigward E, Mignet N, Rat P, Dutot M, Muhamed S, Guigner JM, Scherman D, Brossard D, Crauste-Manciet S - Int J Nanomedicine (2013)

Bottom Line: The multiple emulsion stability was found to increase from 24 hours to 2 and 6 months with Labrasol, glycerol, and Cremophor, respectively.The formulation including glycerol, investigated between 1 and 100 mg/mL concentration of nanoemulsion, did not affect cell viability.This last formulation would therefore be of major interest for further developments.

View Article: PubMed Central - PubMed

Affiliation: Chemical, Genetic and Imaging Pharmacology Laboratory; INSERM U1022, CNRS UMR8151, Chimie ParisTech, Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cité, Paris, France.

ABSTRACT
Three multiple water-in-oil-in-water (W/O/W) nanoemulsions have been designed for potential inclusion of either lipophilic or hydrophilic drugs using a two-step emulsification process exclusively based on low-energy self-emulsification. The W/O primary emulsion was constituted by a blend of oil (medium chain triglyceride), a mixture (7:3) of two surfactants, and a 10% water phase. The surfactants were a mixture of Polysorbate-85/Labrasol(®), Polysorbate-85/Cremophor(®) EL or glycerol/Polysorbate-85. The final W/O/W nanoemulsions were obtained by the addition of water, with a weight ratio nanoemulsion/water of 1:2. The multiple emulsion stability was found to increase from 24 hours to 2 and 6 months with Labrasol, glycerol, and Cremophor, respectively. Cytotoxicity was found for formulations including Labrasol and Cremophor EL. The concentration of emulsion inhibiting 50% cell viability (IC(50)) was determined using the alamarBlue(®) test, giving after 24 hours of incubation, IC(50) = 10.2 mg/mL for the Labrasol formulation and IC(50) = 11.8 mg/mL for the Cremophor EL formulation. Corresponding calculated IC(50) values for surfactants were 0.51 mg/mL for Labrasol and 0.59 mg/mL for Cremophor EL. In both cases, cytotoxicity was due to an apoptotic mechanism, evidenced by chromatin condensation and P2X7 cell death receptor activation. The formulation including glycerol, investigated between 1 and 100 mg/mL concentration of nanoemulsion, did not affect cell viability. Moreover, neither chromatin condensation nor P2X7 activation was found between the 10 and 30 mg/mL final concentration of the emulsion. This last formulation would therefore be of major interest for further developments.

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Pseudoternary phase diagrams of Polysorbate-85/Labrasol®, oil (MCT) and water, with different ratios of Polysorbate-85:Labrasol®. (A) 6:4; (B) 7:3; (C) 8:2; (D) 9:1.Note: ■ = microemulsion phase.Abbreviation: MCT, medium chain triglycerides.
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f3-ijn-8-611: Pseudoternary phase diagrams of Polysorbate-85/Labrasol®, oil (MCT) and water, with different ratios of Polysorbate-85:Labrasol®. (A) 6:4; (B) 7:3; (C) 8:2; (D) 9:1.Note: ■ = microemulsion phase.Abbreviation: MCT, medium chain triglycerides.

Mentions: The results of pseudoternary phase diagram studies performed for Polysorbate-85/Labrasol formulations are shown in Figure 3. Four pseudoternary phase diagrams of surfactant mixtures (Polysorbate-85/Labrasol with ratios of [A] 9:1, [B] 8:2, [C] 7:3, and [D] 6:4), medium chain triglyceride oil, and water were obtained. The diagrams show an increased area of W/O microemulsion zones, with a shifting towards the water rich regions, upon increased ratio of Labrasol in the surfactant/cosurfactant mixture. But the nonmicroemulsion oil dispersion phase formed between oil-surfactant axes and the microemulsion phase increased with the Labrasol ratio. All in all, the surfactant/cosurfactant ratio 7:3 gave the highest microemulsion surface of 20.3% in comparison with 13.9%, 16.3%, and 17.9% obtained for the ratios 6:4, 9:1, and 8:2, respectively.


Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions.

Sigward E, Mignet N, Rat P, Dutot M, Muhamed S, Guigner JM, Scherman D, Brossard D, Crauste-Manciet S - Int J Nanomedicine (2013)

Pseudoternary phase diagrams of Polysorbate-85/Labrasol®, oil (MCT) and water, with different ratios of Polysorbate-85:Labrasol®. (A) 6:4; (B) 7:3; (C) 8:2; (D) 9:1.Note: ■ = microemulsion phase.Abbreviation: MCT, medium chain triglycerides.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569110&req=5

f3-ijn-8-611: Pseudoternary phase diagrams of Polysorbate-85/Labrasol®, oil (MCT) and water, with different ratios of Polysorbate-85:Labrasol®. (A) 6:4; (B) 7:3; (C) 8:2; (D) 9:1.Note: ■ = microemulsion phase.Abbreviation: MCT, medium chain triglycerides.
Mentions: The results of pseudoternary phase diagram studies performed for Polysorbate-85/Labrasol formulations are shown in Figure 3. Four pseudoternary phase diagrams of surfactant mixtures (Polysorbate-85/Labrasol with ratios of [A] 9:1, [B] 8:2, [C] 7:3, and [D] 6:4), medium chain triglyceride oil, and water were obtained. The diagrams show an increased area of W/O microemulsion zones, with a shifting towards the water rich regions, upon increased ratio of Labrasol in the surfactant/cosurfactant mixture. But the nonmicroemulsion oil dispersion phase formed between oil-surfactant axes and the microemulsion phase increased with the Labrasol ratio. All in all, the surfactant/cosurfactant ratio 7:3 gave the highest microemulsion surface of 20.3% in comparison with 13.9%, 16.3%, and 17.9% obtained for the ratios 6:4, 9:1, and 8:2, respectively.

Bottom Line: The multiple emulsion stability was found to increase from 24 hours to 2 and 6 months with Labrasol, glycerol, and Cremophor, respectively.The formulation including glycerol, investigated between 1 and 100 mg/mL concentration of nanoemulsion, did not affect cell viability.This last formulation would therefore be of major interest for further developments.

View Article: PubMed Central - PubMed

Affiliation: Chemical, Genetic and Imaging Pharmacology Laboratory; INSERM U1022, CNRS UMR8151, Chimie ParisTech, Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cité, Paris, France.

ABSTRACT
Three multiple water-in-oil-in-water (W/O/W) nanoemulsions have been designed for potential inclusion of either lipophilic or hydrophilic drugs using a two-step emulsification process exclusively based on low-energy self-emulsification. The W/O primary emulsion was constituted by a blend of oil (medium chain triglyceride), a mixture (7:3) of two surfactants, and a 10% water phase. The surfactants were a mixture of Polysorbate-85/Labrasol(®), Polysorbate-85/Cremophor(®) EL or glycerol/Polysorbate-85. The final W/O/W nanoemulsions were obtained by the addition of water, with a weight ratio nanoemulsion/water of 1:2. The multiple emulsion stability was found to increase from 24 hours to 2 and 6 months with Labrasol, glycerol, and Cremophor, respectively. Cytotoxicity was found for formulations including Labrasol and Cremophor EL. The concentration of emulsion inhibiting 50% cell viability (IC(50)) was determined using the alamarBlue(®) test, giving after 24 hours of incubation, IC(50) = 10.2 mg/mL for the Labrasol formulation and IC(50) = 11.8 mg/mL for the Cremophor EL formulation. Corresponding calculated IC(50) values for surfactants were 0.51 mg/mL for Labrasol and 0.59 mg/mL for Cremophor EL. In both cases, cytotoxicity was due to an apoptotic mechanism, evidenced by chromatin condensation and P2X7 cell death receptor activation. The formulation including glycerol, investigated between 1 and 100 mg/mL concentration of nanoemulsion, did not affect cell viability. Moreover, neither chromatin condensation nor P2X7 activation was found between the 10 and 30 mg/mL final concentration of the emulsion. This last formulation would therefore be of major interest for further developments.

Show MeSH
Related in: MedlinePlus