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

Estelle Sigward,1 Nathalie Mignet,1 Patrice Rat,2 M&eacute;lody Dutot,2 Saleh Muhamed,1 Jean-Michel Guigner,3 Daniel Scherman,1 Denis Brossard,1 Sylvie Crauste-Manciet11Chemical, Genetic and Imaging Pharmacology Laboratory; INSERM U1022, CNRS UMR8151, Chimie ParisTech, Faculty of Pharmacy, P...

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Autores principales:	Sigward E, Mignet N, Rat P, Dutot M, Muhamed S, Guigner JM, Scherman D, Brossard D, Crauste-Manciet S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f3e9d5fb1fb14148b7fddc56b72623f8
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spelling	oai:doaj.org-article:f3e9d5fb1fb14148b7fddc56b72623f82021-12-02T00:22:13ZFormulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions1176-91141178-2013https://doaj.org/article/f3e9d5fb1fb14148b7fddc56b72623f82013-02-01T00:00:00Zhttp://www.dovepress.com/formulation-and-cytotoxicity-evaluation-of-new-self-emulsifying-multip-a12158https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Estelle Sigward,1 Nathalie Mignet,1 Patrice Rat,2 M&eacute;lody Dutot,2 Saleh Muhamed,1 Jean-Michel Guigner,3 Daniel Scherman,1 Denis Brossard,1 Sylvie Crauste-Manciet11Chemical, Genetic and Imaging Pharmacology Laboratory; INSERM U1022, CNRS UMR8151, Chimie ParisTech, Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cit&eacute;, Paris, France; 2Chemistry-Cellular and Analytical Toxicology Laboratory (C-TAC), Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cit&eacute;, Paris, France; 3Institut de Min&eacute;ralogie et de Physique des Milieux Condens&eacute;s IMPMC -IRD-CNRS UMR 7590, Universit&eacute; Paris Pierre et Marie Curie, Paris, FranceAbstract: 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&reg;, Polysorbate-85/ Cremophor&reg; 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 (IC50) was determined using the alamarBlue&reg; test, giving after 24 hours of incubation, IC50 = 10.2 mg/mL for the Labrasol formulation and IC50 = 11.8 mg/mL for the Cremophor EL formulation. Corresponding calculated IC50 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.Keywords: Labrasol, Cremophor EL, apoptosis, P2X7 receptor, polysorbate, glycerolSigward EMignet NRat PDutot MMuhamed SGuigner JMScherman DBrossard DCrauste-Manciet SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 611-625 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Sigward E Mignet N Rat P Dutot M Muhamed S Guigner JM Scherman D Brossard D Crauste-Manciet S Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions
description	Estelle Sigward,1 Nathalie Mignet,1 Patrice Rat,2 M&eacute;lody Dutot,2 Saleh Muhamed,1 Jean-Michel Guigner,3 Daniel Scherman,1 Denis Brossard,1 Sylvie Crauste-Manciet11Chemical, Genetic and Imaging Pharmacology Laboratory; INSERM U1022, CNRS UMR8151, Chimie ParisTech, Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cit&eacute;, Paris, France; 2Chemistry-Cellular and Analytical Toxicology Laboratory (C-TAC), Faculty of Pharmacy, Paris Descartes University, Sorbone Paris Cit&eacute;, Paris, France; 3Institut de Min&eacute;ralogie et de Physique des Milieux Condens&eacute;s IMPMC -IRD-CNRS UMR 7590, Universit&eacute; Paris Pierre et Marie Curie, Paris, FranceAbstract: 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&reg;, Polysorbate-85/ Cremophor&reg; 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 (IC50) was determined using the alamarBlue&reg; test, giving after 24 hours of incubation, IC50 = 10.2 mg/mL for the Labrasol formulation and IC50 = 11.8 mg/mL for the Cremophor EL formulation. Corresponding calculated IC50 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.Keywords: Labrasol, Cremophor EL, apoptosis, P2X7 receptor, polysorbate, glycerol
format	article
author	Sigward E Mignet N Rat P Dutot M Muhamed S Guigner JM Scherman D Brossard D Crauste-Manciet S
author_facet	Sigward E Mignet N Rat P Dutot M Muhamed S Guigner JM Scherman D Brossard D Crauste-Manciet S
author_sort	Sigward E
title	Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions
title_short	Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions
title_full	Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions
title_fullStr	Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions
title_full_unstemmed	Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions
title_sort	formulation and cytotoxicity evaluation of new self-emulsifying multiple w/o/w nanoemulsions
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/f3e9d5fb1fb14148b7fddc56b72623f8
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Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions

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