Nanoparticles and nanocapsules created using the Ouzo effect: spontaneous emulisification as an alternative to ultrasonic and high-shear devices.

The preparation of polymeric particles and capsules by means of spontaneous droplet formation and subsequent polymer precipitation or synthesis is well-known. However, spontaneous emulsification is a phenomenon that has often been erroneously interpreted. This Minireview provides new insights into the preparation of metastable liquid dispersions by homogeneous liquid-liquid nucleation, and is based primarily on a recent study by Vitale and Katz (Langmuir, 2003, 19, 4105-4110). This spontaneous emulsification, which they named the Ouzo effect, occurs upon pouring, into water, a mixture of a totally water-miscible solvent and a hydrophobic oil--and optionally some water--thus generating long-lived small droplets, which are formed even though no surfactant is present. Herein, we review and reinterpret the most relevant publications on the synthesis of a variety of dispersions (pseudolatexes, silicone emulsions, biodegradable polymeric nanocapsules, etc.), which we believe have actually been synthesized using the Ouzo effect. The Ouzo effect may also become a substitute for high-shear techniques, which, to date have only been of limited utility on industrial scales.

[1]  Je Young Kim,et al.  Liquid-liquid phase separation in polysulfone/solvent/water systems , 1997 .

[2]  W. Yu,et al.  A novel approach to the preparation of injectable emulsions by a spontaneous emulsification process , 1993 .

[3]  J. Argillier,et al.  Preparation of oily core polyamide microcapsules via interfacial polycondensation , 2003 .

[4]  Hatem Fessi,et al.  Nanocapsule formation by interfacial polymer deposition following solvent displacement , 1989 .

[5]  Christine Vauthier,et al.  Pegylated Nanoparticles from a Novel Methoxypolyethylene Glycol Cyanoacrylate-Hexadecyl Cyanoacrylate Amphiphilic Copolymer , 1998, Pharmaceutical Research.

[6]  W. Stöber,et al.  Controlled growth of monodisperse silica spheres in the micron size range , 1968 .

[7]  V. Lenaerts,et al.  Preparation and purification of polyisohexylcyanoacrylate nanocapsules , 1991 .

[8]  S. Feng,et al.  Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. , 2004, Biomaterials.

[9]  N. Behan,et al.  The mechanism of polymerisation of butyl cyanoacrylate in aqueous dispersions , 2000 .

[10]  Ilia Fishbein,et al.  Lipophilic drug loaded nanospheres prepared by nanoprecipitation: effect of formulation variables on size, drug recovery and release kinetics. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[11]  H. Fessi,et al.  Preparation of pseudolatex by nanoprecipitation: Influence of the solvent nature on intrinsic viscosity and interaction constant , 1997 .

[12]  Dominique Duchêne,et al.  Development of a new colloidal drug carrier from chemically-modified cyclodextrins: Nanospheres and influence of physicochemical and technological factors on particle size , 1996 .

[13]  S. Davis,et al.  Molecular weights of poly(butyl 2‐cyanoacrylate) produced during nanoparticle formation , 1985 .

[14]  S. Stainmesse,et al.  Formation and stabilization of a biodegradable polymeric colloidal suspension of nanoparticles , 1995 .

[15]  M. Levi,et al.  Aqueous polyurethane dispersions: A comparative study of polymerization processes , 2003 .

[16]  Clarence A. Miller Spontaneous emulsification produced by diffusion. A review , 1988 .

[17]  D. Dieterich Aqueous emulsions, dispersions and solutions of polyurethanes; synthesis and properties , 1981 .

[18]  P. Couvreur,et al.  Preparation and Characterization of Novel Poly(methylidene Malonate 2.1.2.)-Made Nanoparticles , 1994, Pharmaceutical Research.

[19]  E. Korn,et al.  Single bilayer liposomes prepared without sonication. , 1973, Biochimica et biophysica acta.

[20]  D. Shah,et al.  Spontaneous Emulsification: Mechanisms, Physicochemical Aspects, Modeling, and Applications , 2002 .

[21]  G. Messing,et al.  Synthesis of spherical silica particles by spontaneous emulsification , 1992 .

[22]  Elias Fattal,et al.  Nanocapsule technology: a review. , 2002, Critical reviews in therapeutic drug carrier systems.

[23]  J. Lieto,et al.  New approach of the Preparation of Nanocapsules by an Interfacial Polycondensation Reaction , 2003 .

[24]  K. Landfester,et al.  Polyester synthesis in aqueous miniemulsion , 2003 .

[25]  P. Couvreur,et al.  Polycyanoacrylate nanocapsules as potential lysosomotropic carriers: preparation, morphological and sorptive properties , 1979, The Journal of pharmacy and pharmacology.

[26]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[27]  P. Couvreur,et al.  Study of the mechanisms of formation of nanoparticles and nanocapsules of polyisobutyl-2-cyanoacrylate , 1993 .

[28]  Sung-young Park,et al.  Polyurea microcapsules with different structures: Preparation and properties , 2000 .

[29]  V. Lenaerts,et al.  Poly(Alkylcyanoacrylate) Nanocapsules: Physicochemical Characterization and Mechanism of Formation , 1994, Pharmaceutical Research.

[30]  Xuefei Sun,et al.  Preparation of polymer microspheres from solutions , 2003 .

[31]  K. Landfester Polyreactions in miniemulsions. , 2001 .

[32]  Yoshiaki,et al.  Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method. , 1999, International journal of pharmaceutics.

[33]  P. Legrand,et al.  Poly(D,L-lactide) nanocapsules prepared by a solvent displacement process: influence of the composition on physicochemical and structural properties. , 2000, Journal of pharmaceutical sciences.

[34]  E. Perrier,et al.  Synthesis and characterization of polyurethane and poly(ether urethane) nanocapsules using a new technique of interfacial polycondensation combined to spontaneous emulsification. , 2004, International journal of pharmaceutics.

[35]  J. Poupaert,et al.  Poly(diethyl methylidenemalonate) nanoparticles as a potential drug carrier: preparation, distribution and elimination after intravenous and peroral administration to mice. , 1991, Journal of pharmaceutical sciences.

[36]  M. Šen,et al.  Amphiphilic beta-cyclodextrins modified on the primary face: synthesis, characterization, and evaluation of their potential as novel excipients in the preparation of nanocapsules. , 2002, Journal of pharmaceutical sciences.

[37]  M. Antonietti,et al.  Polyaddition in miniemulsions: A new route to polymer dispersions. , 2000 .

[38]  P. Gramain,et al.  PREPARATION OF POLYURETHANE MICROCAPSULES BY INTERFACIAL POLYCONDENSATION , 1998 .

[39]  B. Vincent,et al.  Novel monodisperse silicone oil/water emulsions , 1994 .

[40]  P. Hémery,et al.  Anionic Polymerization of n-Butyl Cyanoacrylate in Emulsion and Miniemulsion , 2003 .

[41]  M. Lynch,et al.  Novel Process for Producing Cubic Liquid Crystalline Nanoparticles (Cubosomes) , 2001 .

[42]  M. Georges,et al.  Stable Free-Radical Emulsion Polymerization , 2004 .

[43]  H. Fessi,et al.  Physicochemical Parameters Associated with Nanoparticle Formation in the Salting-Out, Emulsification-Diffusion, and Nanoprecipitation Methods , 2004, Pharmaceutical Research.

[44]  K. Landfester,et al.  High Molecular Weight Polyurethane and Polymer Hybrid Particles in Aqueous Miniemulsion , 2003 .

[45]  Y. I. Kim,et al.  Preparation and characterization of nanoparticles containing an antihypertensive agent. , 1998, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[46]  J. Katz,et al.  Liquid Droplet Dispersions Formed by Homogeneous Liquid−Liquid Nucleation: “The Ouzo Effect” , 2003 .

[47]  Clarence A. Miller,et al.  Spontaneous Emulsification in Ternary Systems with Mass Transfer , 1972 .

[48]  R. Bodmeier,et al.  Spontaneous formation of drug-containing acrylic nanoparticles. , 1991, Journal of microencapsulation.

[49]  G. Giammona,et al.  Influence of the preparation conditions on poly(ethylcyanoacrylate) nanocapsule formation , 1995 .

[50]  E. Perrier,et al.  Nano-emulsion formulation using spontaneous emulsification: solvent, oil and surfactant optimisation. , 2004, International journal of pharmaceutics.

[51]  N. Zydowicz,et al.  Formation of aqueous core polyamide microcapsules obtained via interfacial polycondensation , 2001 .