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Article Dans Une Revue International Journal of Nanomedicine Année : 2013

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

Résumé

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 Cre-mophor 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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hal-01583935 , version 1 (08-09-2017)

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Estelle Sigward, Nathalie Mignet, Patrice Rat, Melody Dutot, Saleh Muhamed, et al.. Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions. International Journal of Nanomedicine, 2013, 8, pp.611 - 625. ⟨10.2147/IJN.S35661⟩. ⟨hal-01583935⟩
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