Formation d'émulsions multiples stimulables en une seule étape d'émulsification : effet du sel et évolution vers des architectures biocompatibles

We studied stimuli-responsive multiple emulsions formed in a one-step mechanical emulsification process. These emulsions are stabilized by amphiphilic copolymers synthesized by atom transfer radical polymerization. Depending on pH, ionic strength and temperature, different emulsion types can be obtained, including water-continuous (W/O/W) and oil-continuous (O/W/O) multiple emulsions. These emulsions are stable during several months.We formed W/O/W emulsions with two entirely biocompatible systems using a poly(dimethylsiloxane)-b-poly(dimethylaminoethyl methacrylate) copolymer. Water/Miglyol® 812/water emulsions formulated with this copolymer enable the encapsulation and controlled release of hydrophilic species with the three stimuli: pH, ionic strength and temperature.Furthermore, we studied the formation conditions of multiple water – toluene – polystyrene-b-poly(styrene-st-dimethylaminoethyl methacrylate) emulsions. We probed the conformation of the polymer adsorbed at the water – oil interface using neutron reflectivity. Our results show an existing correlation between emulsion type and polymer conformation. Moreover, the formation of multiple emulsions is promoted by a decrease in the curvature of the microemulsions formed in water, which was assessed by cryo transmission electron microscopy and small angle neutron scattering. Finally, we settled predictive criteria for the formation of multiple emulsions. These criteria are based on interfacial tension and polymer partitioning measurements.Nous nous sommes intéressés aux émulsions multiples stimulables formées en une étape d’émulsification mécanique. Ces émulsions sont stabilisées par des copolymères amphiphiles synthétisés par polymérisation radicalaire contrôlée par transfert d’atome. L’ajustement du pH et de la force ionique permet la préparation de différents types d’émulsion, dont des émulsions multiples à phase eau (E/H/E) ou huile (H/E/H) continue qui sont stables sur plusieurs mois.Nous avons étudié deux systèmes entièrement biocompatibles permettant la formation d’émulsions E/H/E stabilisées par un unique copolymère, de type poly(diméthylsiloxane)-b-poly(méthacrylate de diméthylamino éthyle). Les émulsions eau/ Miglyol® 812/eau ainsi formulées permettent l’encapsulation et la libération contrôlée de composés hydrophiles par les trois stimuli : pH, force ionique et température.Par ailleurs, nous nous sommes intéressés aux conditions de formation d’émulsions multiples à partir d’un système modèle eau – toluène – polystyrène-b-poly(styrène-st-méthacrylate de diméthylamino éthyle). Nous avons sondé la conformation du copolymère à l’interface eau – huile par réflectivité de neutrons. Les résultats obtenus montrent une corrélation entre cette conformation et le type d’émulsion. De plus, l’obtention d’émulsions multiples est favorisée par la réduction de la courbure des microémulsions formées dans l’eau, telles qu’étudiées par cryo-microscopie électronique à transmission et diffusion de neutrons aux petits angles. Enfin, des critères prédictifs de la formation d’émulsions multiples ont été obtenus grâce à des mesures de tension interfaciale et du partitionnement du copolymère entre les deux phase

Formation of stimuli-responsive multiple emulsions in a one-step emulsification process : effect of ionic strength and evolution towards biocompatibility

Nous nous sommes intéressés aux émulsions multiples stimulables formées en une étape d’émulsification mécanique. Ces émulsions sont stabilisées par des copolymères amphiphiles synthétisés par polymérisation radicalaire contrôlée par transfert d’atome. L’ajustement du pH et de la force ionique permet la préparation de différents types d’émulsion, dont des émulsions multiples à phase eau (E/H/E) ou huile (H/E/H) continue qui sont stables sur plusieurs mois. Nous avons étudié deux systèmes entièrement biocompatibles permettant la formation d’émulsions E/H/E stabilisées par un unique copolymère, de type poly(diméthylsiloxane)-b-poly(méthacrylate de diméthylamino éthyle). Les émulsions eau/ Miglyol® 812/eau ainsi formulées permettent l’encapsulation et la libération contrôlée de composés hydrophiles par les trois stimuli : pH, force ionique et température. Par ailleurs, nous nous sommes intéressés aux conditions de formation d’émulsions multiples à partir d’un système modèle eau – toluène – polystyrène-b-poly(styrène-st-méthacrylate de diméthylamino éthyle). Nous avons sondé la conformation du copolymère à l’interface eau – huile par réflectivité de neutrons. Les résultats obtenus montrent une corrélation entre cette conformation et le type d’émulsion. De plus, l’obtention d’émulsions multiples est favorisée par la réduction de la courbure des microémulsions formées dans l’eau, telles qu’étudiées par cryo-microscopie électronique à transmission et diffusion de neutrons aux petits angles. Enfin, des critères prédictifs de la formation d’émulsions multiples ont été obtenus grâce à des mesures de tension interfaciale et du partitionnement du copolymère entre les deux phases.We studied stimuli-responsive multiple emulsions formed in a one-step mechanical emulsification process. These emulsions are stabilized by amphiphilic copolymers synthesized by atom transfer radical polymerization. Depending on pH, ionic strength and temperature, different emulsion types can be obtained, including water-continuous (W/O/W) and oil-continuous (O/W/O) multiple emulsions. These emulsions are stable during several months. We formed W/O/W emulsions with two entirely biocompatible systems using a poly(dimethylsiloxane)-b-poly(dimethylaminoethyl methacrylate) copolymer. Water/Miglyol® 812/water emulsions formulated with this copolymer enable the encapsulation and controlled release of hydrophilic species with the three stimuli: pH, ionic strength and temperature. Furthermore, we studied the formation conditions of multiple water – toluene – polystyrene-b-poly(styrene-st-dimethylaminoethyl methacrylate) emulsions. We probed the conformation of the polymer adsorbed at the water – oil interface using neutron reflectivity. Our results show an existing correlation between emulsion type and polymer conformation. Moreover, the formation of multiple emulsions is promoted by a decrease in the curvature of the microemulsions formed in water, which was assessed by cryo transmission electron microscopy and small angle neutron scattering. Finally, we settled predictive criteria for the formation of multiple emulsions. These criteria are based on interfacial tension and polymer partitioning measurements

Emulsions multiples stimulables pour l’encapsulation et la libération contrôlée de principes actifs

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Can we predict emulsion nature by thermodynamics?

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Simple and multiple emulsions stabilized by charged-neutral copolymers

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Formulation of stimulable multiple emulsions by microfluidics

International audienceMultiple emulsions, in particular water-in-oil-in-water (w/o/w) emulsions, are promising systems for encapsulation and controIled delivery of drugs. We developed a new emulsifier, a poly(dimethylsiloxane)-b-poly(dimethylaminoethylmethacrylate) (PDMS-b-PDMAEMA) amphiphilic copolymer, capable of stabilizing multiple emulsions in one mixing step over long times. This polymer is stimuli responsive, aIlowing the formation of direct, inverse and w/o/w emulsions depending on the pH and ionic strength. It is then possible to consider the controIled release of a compound encapsulated in the inner water droplets.However it is highly desirable to both form monodisperse emulsions for reaching a reliable control of the delivery and differentiate the inner water phases carrying the cargo from the external water phase for avoiding tediol}s washing steps. For aIl these reasons microfluidics was considered as a promising tool and is shown here to provide first promising results

Stimulable, stable and biocompatible W/O/W emulsions for encapsulation and controlled delivery of drugs

International audienceFoams and emulsions Water-in-oil-in-water (w/o/w) emulsions are promising systems for encapsulation and controlled delivery of drugs. A new amphiphilic copolymer (PDMS-$b$-PDMAEMA) was developed as an emulsifier for preventing the notorious instability of those emulsions and was capable of stabilizing multiple emulsions for more than a year. This polymer is stimuli responsive, allowing the formation in a single mixing step, of direct, inverse and w/o/w emulsions, depending on the pH and ionic strength of the aqueous phase. Consequently, by changing pH, w/o/w emulsions can be destabilized and a compound encapsulated in the internal water phase is released in a controlled way. The use of microfluidic PDMS chips for a better control of the size and the morphology of the emulsions was also studied. The aim is to use this promising system to coencapsulate and protect two molecules of interest for health: catechin, an hydrophilic molecule from green tea, and curcumin, an hydrophobic molecule from turmeric. These two antioxidants have lots of potential health benefits but are very fragile and difficult to deliver: formulating them in a double emulsion will allow to preserve them during storage and should improve the absorption

Formulation d'émulsions multiples stables, stimulables et biocompatibles

International audienceLes émulsions eau-dans-huile-dans-eau (E/H/E) constituent des vecteurs intéressants pour l'encapsulation et le relargage contrôlé de principes actifs. Nous avons développé un copolymère amphiphile (PDMS-b-PDMAEMA) capable de former ce type d'émulsions en une seule étape, et de les stabiliser pendant plus d'une année, bien qu'elles soient connues pour leur manque de stabilité lorsqu'elles sont formulées plus classiquement en deux étapes. Le copolymère utilisé est aussi sensible au pH et à la force ionique, ce qui nous permet, en faisant varier ces deux paramètres, de former des émulsions directes, E/H/E ou inverses, et de provoquer la déstabilisation contrôlée de nos émulsions grâce à une variation de pH. Enfin, notre polymère est biocompatible et nous envisageons donc de développer des applications pour l'homme. Notre but final serait d'utiliser notre système pour coencapsuler une molécule hydrophile et une molécule hydrophobe au sein de la même émulsion double, pour les protéger de l'oxydation durant le stockage, et pouvoir les relarguer de façon contrôlée lors de leur arrivée dans l'estomac où le pH diminue. Nous présenterons des premiers tests d'encapsulation d'une molécule modèle, le saccharose, ainsi que d'un antioxydant venant du thé vert, la catéchine. Deux modes d'émulsification seront aussi décrits: la voie mécanique, classique, et la voie microfluidique

Biocompatible Stimuli-Responsive W/O/W Multiple Emulsions Prepared by One-Step Mixing with a Single Diblock Copolymer Emulsifier

International audienceMultiple water-in-oil-in-water (W/O/W) emulsions are promising materials in designing carriers of hydrophilic molecules or drug delivery systems, provided stability issues are solved and biocompatible chemicals can be used. In this work, we designed a biocompatible amphiphilic copolymer, poly(dimethylsiloxane)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMS-b-PDMAE-MA), that can stabilize emulsions made with various biocompatible oils. The hydrophilic/hydrophobic properties of the copolymer can be adjusted using both pH and ionic strength stimuli. Consequently, the making of O/W (oil in water), W/O (water in oil), and W/O/W emulsions can be achieved by sweeping the pH and ionic strength. Of importance, W/O/W emulsions are formulated over a large pH and ionic strength domain in a one-step emulsification process via transitional phase inversion and are stable for several months. Cryo-TEM and interfacial tension studies show that the formation of these W/O/W emulsions is likely to be correlated to the interfacial film curvature and microemulsion morphology

One-step formation of stable multiple emulsions

International audienceStimuli-responsive multiple emulsions formed in a one-step mechanical emulsification process are shown to be stable for months. These emulsions are stabilized by amphiphilic copolymers synthesized by atom transfer radical polymerization (ATRP). Depending on pH, ionic strength and temperature, different emulsion types are obtained, including water-continuous (W/O/W) and oil-continuous (O/W/O) multiple emulsions. In particular W/O/W emulsions can be formed with biocompatible molecules like poly(dimethylsiloxane)-bpoly(dimethylaminoethyl methacrylate) copolymer and Miglyol® 812 as an oil phase. These emulsions enable the encapsulation and controlled release of hydrophilic species with the three stimuli: pH, ionic strength and temperature.Furthermore, we studied the formation conditions of multiple water – toluene – polystyrene-b-poly(styrene-st-dimethylaminoethyl methacrylate) emulsions. The conformation of the polymer adsorbed at the water – oil interface was probed using an original neutron reflectivity set-up. Our results evidence a correlation between emulsion type and polymer conformation. More precisely, the formation of multiple emulsions is promoted by a decrease in the curvature of the microemulsions formed in water, in agreement with cryo transmission electron microscopy and small angle neutron scattering. Finally, we exhibit predictive criteria for the formation of multiple emulsions based on interfacial tension and polymer partitioning measurement