Multiple nanoemulsions

Abstract

The structural and chemical uniformity of traditional emulsions facilitates their production; however, this simplicity also limits the scope of their applications. Multiphase or ‘multiple’ emulsions have increased complexity and potentially broader utility than conventional emulsions, owing to their internalized phases, enabling chemical compartmentalization, control of active-ingredient release and complex particle templates. However, multiple-emulsion droplets prepared with conventional methods are too large for emerging applications. As a result, there has been increased research interest in the development of multiple nanoemulsions, whereby the nanoscale droplet size overcomes many of the limitations of more common, micrometre-scale multiple emulsions. Although numerous successful demonstrations of multiple-nanoemulsion production have emerged, there remain considerable challenges to improve stability, control over internal structure and characterization of multiphase nanodroplets. Overcoming these challenges provides unique opportunities to exploit the hierarchical structure, enhanced colloidal stability and multiphase chemical solubilization for applications, such as delivery vehicles, chemical sinks and particle templates, with functions that are otherwise inaccessible. In this Review, we summarize the techniques used to generate and characterize multiple nanoemulsions, theories to understand their formation and stability, and discuss current and future applications that are, or may be, enabled by their unique structures and chemistries.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Overview of different classes of emulsions.
Fig. 2: A design space of multiphase emulsions.
Fig. 3: Schematic illustration of the techniques used to generate multiple nanoemulsions.
Fig. 4: Potential mechanisms governing the instability of multiple nanoemulsions.
Fig. 5: Design features of multiple nanoemulsions.

References

  1. 1.

    Brummer, R. & Godersky, S. Rheological studies to objectify sensations occurring when cosmetic emulsions are applied to the skin. Colloids Surf. A 152, 89–94 (1999).

  2. 2.

    Gilbert, L., Picard, C., Savary, G. & Grisel, M. Rheological and textural characterization of cosmetic emulsions containing natural and synthetic polymers: relationships between both data. Colloids Surf. A 421, 150–163 (2013).

  3. 3.

    O’Toole, J. T. Kinetics of emulsion polymerization. J. Appl. Polym. Sci. 9, 1291–1297 (1965).

  4. 4.

    Wang, L., Li, X., Zhang, G., Dong, J. & Eastoe, J. Oil-in-water nanoemulsions for pesticide formulations. J. Colloid Interface Sci. 314, 230–235 (2007).

  5. 5.

    Hainey, P., Huxham, I. M., Rowatt, B., Sherrington, D. C. & Tetley, L. Synthesis and ultrastructural studies of styrene-divinylbenzene polyhipe polymers. Macromolecules 24, 117–121 (1991).

  6. 6.

    Pileni, M.-P. The role of soft colloidal templates in controlling the size and shape of inorganic nanocrystals. Nat. Mater. 2, 145–150 (2003).

  7. 7.

    Bhumgara, Z. Polyhipe foam materials as filtration media. Filtr. Sep. 32, 245–251 (1995).

  8. 8.

    Helgeson, M. E. Colloidal behavior of nanoemulsions: interactions, structure, and rheology. Curr. Opin. Colloid Interface Sci. 25, 39–50 (2016).

  9. 9.

    Jaiswal, M., Dudhe, R. & Sharma, P. K. Nanoemulsion: an advanced mode of drug delivery system. 3 Biotech 5, 123–127 (2015).

  10. 10.

    Donalisio, M. et al. Acyclovir-loaded chitosan nanospheres from nano-emulsion templating for the topical treatment of herpesviruses infections. Pharmaceutics 10, 46 (2018).

  11. 11.

    Mahmood, T., Akhtar, N. & Manickam, S. Interfacial film stabilized W/O/W nano multiple emulsions loaded with green tea and lotus extracts: systematic characterization of physicochemical properties and shelf-storage stability. J. Nanobiotechnol. 12, 20 (2014).

  12. 12.

    Datta, S. S. et al. Double emulsion templated solid microcapsules: mechanics and controlled release. Adv. Mater. 26, 2205–2218 (2014).

  13. 13.

    Silva, B. F. B., Rodríguez-Abreu, C. & Vilanova, N. Recent advances in multiple emulsions and their application as templates. Curr. Opin. Colloid Interface Sci. 25, 98–108 (2016).

  14. 14.

    Abate, A. R. & Weitz, D. A. High-order multiple emulsions formed in poly(dimethylsiloxane) microfluidics. Small 5, 2030–2032 (2009).

  15. 15.

    Allouche, J., Tyrode, E., Sadtler, V., Choplin, L. & Salager, J.-L. Single- and two-step emulsification to prepare a persistent multiple emulsion with a surfactant–polymer mixture. Ind. Eng. Chem. Res. 42, 3982–3988 (2003).

  16. 16.

    Kim, S., Kim, K. & Choi, S. Q. Controllable one-step double emulsion formation via phase inversion. Soft Matter 14, 1094–1099 (2018).

  17. 17.

    Min, J.-Y., Ahn, S.-I., Lee, Y.-K., Kwak, H.-S. & Chang, Y. H. Optimized conditions to produce water-in-oil-in-water nanoemulsion and spray-dried nanocapsule of red ginseng extract. Food Science Technol. 38, 485–492 (2018).

  18. 18.

    Mason, T. G., Graves, S. M., Wilking, J. N. & Lin, M. Y. Extreme emulsification: formation and structure of nanoemulsions. Condens. Matter Phys. 9, 193–199 (2006).

  19. 19.

    McClements, D. J. & Rao, J. Food-grade nanoemulsions: formulation, fabrication, properties, performance, biological fate, and potential toxicity. Crit. Rev. Food Sci. Nutr. 51, 285–330 (2011).

  20. 20.

    Mason, T. G., Wilking, J. N., Meleson, K., Chang, C. B. & Graves, S. M. Nanoemulsions: formation, structure, and physical properties. J. Phys. Condens. Matter 18, R635–R666 (2006).

  21. 21.

    Bilati, U., Allémann, E. & Doelker, E. Sonication parameters for the preparation of biodegradable nanocapsules of controlled size by the double emulsion method. Pharm. Dev. Technol. 8, 1–9 (2003).

  22. 22.

    Koroleva, M. Y. & Yurtov, E. V. Nanoemulsions: the properties, methods of preparation and promising applications. Russ. Chem. Rev. 81, 21–43 (2012).

  23. 23.

    Solans, C. & Solé, I. Nano-emulsions: formation by low-energy methods. Curr. Opin. Colloid Interface Sci. 17, 246–254 (2012).

  24. 24.

    Forgiarini, A., Esquena, J., González, C. & Solans, C. Formation of nano-emulsions by low-energy emulsification methods at constant temperature. Langmuir 17, 2076–2083 (2001).

  25. 25.

    Anton, N. & Vandamme, T. F. The universality of low-energy nano-emulsification. Int. J. Pharm. 377, 142–147 (2009). An adept description of the single, surfactant-driven mechanism through which spontaneous emulsification occurs, regardless of concentration or temperature driving force.

  26. 26.

    Gupta, A., Badruddoza, A. Z. M. & Doyle, P. S. A general route for nanoemulsion synthesis using low-energy methods at constant temperature. Langmuir 33, 7118–7123 (2017).

  27. 27.

    Izquierdo, P. et al. Formation and stability of nano-emulsions prepared using the phase inversion temperature method. Langmuir 18, 26–30 (2002).

  28. 28.

    Leitner, S., Solans, C., García-Celma, M. J. & Calderó, G. Low-energy nano-emulsification approach as a simple strategy to prepare positively charged ethylcellulose nanoparticles. Carbohydr. Polym. 205, 117–124 (2019).

  29. 29.

    Yang, Y., Marshall-Breton, C., Leser, M. E., Sher, A. A. & McClements, D. J. Fabrication of ultrafine edible emulsions: comparison of high-energy and low-energy homogenization methods. Food Hydrocoll. 29, 398–406 (2012).

  30. 30.

    McClements, D. J. Food Emulsions: Principles, Practices, and Techniques 2nd edn (CRC, 2005).

  31. 31.

    Para, G., Jarek, E., Warszyński, P. & Adamczyk, Z. Effect of electrolytes on surface tension of ionic surfactant solutions. Colloids Surf. A 222, 213–222 (2003).

  32. 32.

    Sainis, S. K., Germain, V., Mejean, C. O. & Dufresne, E. R. Electrostatic interactions of colloidal particles in nonpolar solvents: role of surface chemistry and charge control agents. Langmuir 24, 1160–1164 (2008).

  33. 33.

    Espinosa, C. E., Guo, Q., Singh, V. & Behrens, S. H. Particle charging and charge screening in nonpolar dispersions with nonionic surfactants. Langmuir 26, 16941–16948 (2010).

  34. 34.

    Tadros, T. F. Applied Surfactants: Principles and Applications (Wiley-VCH, 2005).

  35. 35.

    Luan, F. et al. Prediction of hydrophile–lipophile balance values of anionic surfactants using a quantitative structure–property relationship. J. Colloid Interface Sci. 336, 773–779 (2009).

  36. 36.

    Florence, A. T. & Whitehill, D. The formulation and stability of multiple emulsions. Int. J. Pharm. 11, 277–308 (1982).

  37. 37.

    Pal, R. Multiple O/W/O emulsion rheology. Langmuir 12, 2220–2225 (1996).

  38. 38.

    Carlotti, M. E., Gallarate, M., Sapino, S., Ugazio, E. & Morel, S. W/O/W multiple emulsions for dermatological and cosmetic use, obtained with ethylene oxide free emulsifiers. J. Dispers. Sci. Technol. 26, 183–192 (2005).

  39. 39.

    Morais, J. M., Santos, O. D. H., Nunes, J. R. L., Zanatta, C. F. & Rocha-Filho, P. A. W/O/W multiple emulsions obtained by one-step emulsification method and evaluation of the involved variables. J. Dispers. Sci. Technol. 29, 63–69 (2008).

  40. 40.

    Fryd, M. M. & Mason, T. G. Advanced nanoemulsions. Annu. Rev. Phys. Chem. 63, 493–518 (2012).

  41. 41.

    Pawar, A. B., Caggioni, M., Ergun, R., Hartel, R. W. & Spicer, P. T. Arrested coalescence in Pickering emulsions. Soft Matter 7, 7710–7716 (2011).

  42. 42.

    Chevalier, Y. & Bolzinger, M.-A. Emulsions stabilized with solid nanoparticles: Pickering emulsions. Colloids Surf. A 439, 23–34 (2013).

  43. 43.

    Vignati, E., Piazza, R. & Lockhart, T. P. Pickering emulsions: interfacial tension, colloidal layer morphology, and trapped-particle motion. Langmuir 19, 6650–6656 (2003).

  44. 44.

    Lee, Y.-T. et al. Ultrasound-based formation of nano-Pickering emulsions investigated via in-situ SAXS. J. Colloid Interface Sci. 536, 281–290 (2019).

  45. 45.

    Gañán-Calvo, A. M., González-Prieto, R., Riesco-Chueca, P., Herrada, M. A. & Flores-Mosquera, M. Focusing capillary jets close to the continuum limit. Nat. Phys. 3, 737–742 (2007).

  46. 46.

    Saleem, R. & Ahmad, R. Effect of ultrasonication on secondary structure and heat induced gelation of chicken myofibrils. J. Food Sci. Technol. 53, 3340–3348 (2016).

  47. 47.

    Zhang, M. et al. Controlling complex nanoemulsion morphology using asymmetric cosurfactants for the preparation of polymer nanocapsules. Langmuir 34, 978–990 (2018).

  48. 48.

    Helfrich, W. Elastic properties of lipid bilayers: theory and possible experiments. Z. Naturforsch. C 28, 693–703 (1973).

  49. 49.

    Malo de Molina, P., Zhang, M., Bayles, A. V. & Helgeson, M. E. Oil-in-water-in-oil multinanoemulsions for templating complex nanoparticles. Nano Lett. 16, 7325–7332 (2016).

  50. 50.

    Hanson, J. A. et al. Nanoscale double emulsions stabilized by single-component block copolypeptides. Nature 455, 85–88 (2008). This paper demonstrates the use of asymmetric co-surfactants to produce metastable core–shell double nanoemulsions.

  51. 51.

    Fryd, M. M. & Mason, T. G. Cerberus nanoemulsions produced by multidroplet flow-induced fusion. Langmuir 29, 15787–15793 (2013). This paper demonstrates the ability to form high-order structures by increasing the number of immiscible phases within dispersed droplets.

  52. 52.

    Patel, S. K., Zhang, Y., Pollock, J. A. & Janjic, J. M. Cyclooxgenase-2 inhibiting perfluoropoly (ethylene glycol) ether theranostic nanoemulsions—in vitro study. PLOS ONE 8, e55802 (2013). This paper highlights the development of a triphasic fluorocarbon-in-hydrocarbon-in-water core–shell double-nanoemulsion system and demonstrates its use for dual-mode imaging in vitro.

  53. 53.

    Patel, S. K., Patrick, M. J., Pollock, J. A. & Janjic, J. M. Two-color fluorescent (near-infrared and visible) triphasic perfluorocarbon nanoemulsions. J. Biomed. Opt. 18, 101312 (2013).

  54. 54.

    Wu, S., Hung, Y. & Mou, C. Compartmentalized hollow silica nanospheres templated from nanoemulsions. Chem. Mater. 25, 352–364 (2013). This paper highlights the use of interfacial silica polymerization to form nested double nanoemulsions for the potential application of co-encapsulation of water-soluble and oil-soluble drugs.

  55. 55.

    van der Graaf, S., Schroën, C. G. P. H. & Boom, R. M. Preparation of double emulsions by membrane emulsification: a review. J. Membr. Sci. 251, 7–15 (2005).

  56. 56.

    Zambaux, M. F. et al. Influence of experimental parameters on the characteristics of poly(lactic acid) nanoparticles prepared by a double emulsion method. J. Control. Rel. 50, 31–40 (1998).

  57. 57.

    Tang, S. Y., Sivakumar, M. & Nashiru, B. Impact of osmotic pressure and gelling in the generation of highly stable single core water-in-oil-in-water (W/O/W) nano multiple emulsions of aspirin assisted by two-stage ultrasonic cavitational emulsification. Colloids Surf. B 102, 653–658 (2013).

  58. 58.

    Tang, S. Y., Sivakumar, M., Ng, A. M. & Shridharan, P. Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation. Int. J. Pharm. 430, 299–306 (2012).

  59. 59.

    Zhang, M. et al. Synthesis of oil-laden poly(ethylene glycol) diacrylate hydrogel nanocapsules from double nanoemulsions. Langmuir 33, 6116–6126 (2017). This work demonstrates the technique of sequential emulsification and one of the resulting applications enabled by core–shell nanoemulsions — templating of oil-laden hydrogel nanocapsules.

  60. 60.

    Nisisako, T., Okushima, S. & Torii, T. Controlled formulation of monodisperse double emulsions in a multiple-phase microfluidic system. Soft Matter 1, 23–27 (2005).

  61. 61.

    Chu, L.-Y., Utada, A. S., Shah, R. K., Kim, J. W. & Weitz, D. A. Controllable monodisperse multiple emulsions. Angew. Chem. Int. Ed. 46, 8970–8974 (2007).

  62. 62.

    Zhang, M.-Y., Zhao, H., Xu, J.-H. & Luo, G.-S. Controlled coalescence of two immiscible droplets for Janus emulsions in a microfluidic device. RSC Adv. 5, 32768–32774 (2015).

  63. 63.

    Park, J., Forster, J. D. & Dufresne, E. R. High-yield synthesis of monodisperse dumbbell-shaped polymer nanoparticles. J. Am. Chem. Soc. 132, 5960–5961 (2010).

  64. 64.

    Li, J. et al. A dewetting route to grow heterostructured nanoparticles based on thin film heterojunctions. Nanoscale 7, 19977–19984 (2015).

  65. 65.

    Lu, Y. et al. Asymmetric dimers can be formed by dewetting half-shells of gold deposited on the surfaces of spherical oxide colloids. J. Am. Chem. Soc. 125, 12724–12725 (2003).

  66. 66.

    Oh, C., Park, J., Shin, S. & Oh, S. O/W/O multiple emulsions via one-step emulsification process. J. Dispers. Sci. Technol. 25, 53–62 (2004).

  67. 67.

    Galindo-Alvarez, J., Sadtler, V., Choplin, L. & Salager, J.-L. Viscous oil emulsification by catastrophic phase inversion: influence of oil viscosity and process conditions. Ind. Eng. Chem. Res. 50, 5575–5583 (2011).

  68. 68.

    Liu, Y., Carter, E. L., Gordon, G. V., Feng, Q. J. & Friberg, S. E. An investigation into the relationship between catastrophic inversion and emulsion phase behaviors. Colloids Surf. A 399, 25–34 (2012).

  69. 69.

    Sigward, E. et al. Formulation and cytotoxicity evaluation of new self-emulsifying multiple W/O/W nanoemulsions. Int. J. Nanomed. 8, 611–625 (2013).

  70. 70.

    Shakeel, F., Haq, N., Al-Dhfyan, A., Alanazi, F. K. & Alsarra, I. A. Double w/o/w nanoemulsion of 5-fluorouracil for self-nanoemulsifying drug delivery system. J. Mol. Liq. 200, 183–190 (2014).

  71. 71.

    Sigward, E. et al. Preparation and evaluation of multiple nanoemulsions containing gadolinium (III) chelate as a potential magnetic resonance imaging (MRI) contrast agent. Pharm. Res. 32, 2983–2994 (2015).

  72. 72.

    Pangeni, R., Choi, S. W., Jeon, O.-C., Byun, Y. & Park, J. W. Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation. Int. J. Nanomed. 11, 6379–6399 (2016).

  73. 73.

    Ding, S. et al. A new method for the formulation of double nanoemulsions. Soft Matter 13, 1660–1669 (2017). W/O/W double nanoemulsions are produced using an emulsification process involving a primary step of high-pressure homogenization to generate a W/O nanoemulsion, followed by spontaneous emulsification of the W/O nanoemulsion in water to stabilize W/O/W core–shell droplets.

  74. 74.

    Lee, H. S., Morrison, E. D., Frethem, C. D., Zasadzinski, J. A. & McCormick, A. V. Cryogenic electron microscopy study of nanoemulsion formation from microemulsions. Langmuir 30, 10826–10833 (2014).

  75. 75.

    Lee, H. S., Morrison, E. D., Zhang, Q. & McCormick, A. V. Cryogenic transmission electron microscopy study: preparation of vesicular dispersions by quenching microemulsions. J. Microsc. 263, 293–299 (2016). This study describes the technique of temperature-induced and concentration-induced microemulsion phase inversion to form core–shell and nested double nanoemulsions.

  76. 76.

    Zhao, Y., Zhang, J., Wang, Q., Li, J. & Han, B. Water-in-oil-in-water double nanoemulsion induced by CO2. Phys. Chem. Chem. Phys. 13, 684–689 (2011).

  77. 77.

    Tiarks, F., Landfester, K. & Antonietti, M. Preparation of polymeric nanocapsules by miniemulsion polymerization. Langmuir 17, 908–918 (2001). The demonstration that core–shell and lens-type droplets arise through dewetting of a monomer solution from polymerizing particles during nanoparticle synthesis.

  78. 78.

    Grundy, L. S. et al. Rapid production of internally structured colloids by flash nanoprecipitation of block copolymer blends. ACS Nano 12, 4660–4668 (2018).

  79. 79.

    Lin, T. J. Low-energy emulsification I: Principles and applications. J. Soc. Cosmet. Chem. 29, 117–125 (1978).

  80. 80.

    Komaiko, J. S. & McClements, D. J. Optimization of isothermal low-energy nanoemulsion formation: hydrocarbon oil, non-ionic surfactant, and water systems. J. Colloid Interface Sci. 425, 59–66 (2014).

  81. 81.

    Komaiko, J. S. & McClements, D. J. Low-energy formation of edible nanoemulsions by spontaneous emulsification: factors influencing particle size. J. Food Eng. 146, 122–128 (2015).

  82. 82.

    Komaiko, J. S. & McClements, D. J. Formation of food-grade nanoemulsions using low-energy preparation methods: a review of available methods. Compr. Rev. Food Sci. Food Saf. 15, 331–352 (2016).

  83. 83.

    Provencher, S. W. A constrained regularization method for inverting data represented by linear algebraic or integral equations. Comput. Phys. Commun. 27, 213–227 (1982).

  84. 84.

    Thomas, D. G. Transport characteristics of suspension: VIII. A note on the viscosity of Newtonian suspensions of uniform spherical particles. J. Colloid Sci. 20, 267–277 (1965).

  85. 85.

    Tadros, T. F., Izquierdo, P., Esquena, J. & Solans, C. Formation and stability of nano-emulsions. Adv. Colloid Interface Sci. 108–109, 303–318 (2004).

  86. 86.

    Gupta, A., Eral, H. B., Hatton, T. A. & Doyle, P. S. Nanoemulsions: formation, properties and applications. Soft Matter 12, 2826–2841 (2016).

  87. 87.

    McClements, D. J. Nanoemulsions versus microemulsions: terminology, differences, and similarities. Soft Matter 8, 1719–1729 (2012).

  88. 88.

    Matalanis, A., Jones, O. G. & McClements, D. J. Structured biopolymer-based delivery systems for encapsulation, protection, and release of lipophilic compounds. Food Hydrocoll. 25, 1865–1880 (2011).

  89. 89.

    Qian, J. & Law, C. K. Regimes of coalescence and separation in droplet collision. J. Fluid Mech. 331, 59–80 (1997).

  90. 90.

    Leal, L. G. Flow induced coalescence of drops in a viscous fluid. Phys. Fluids 16, 1833–1851 (2004).

  91. 91.

    Baldessari, F. & Leal, L. G. Effect of overall drop deformation on flow-induced coalescence at low capillary numbers. Phys. Fluids 18, 013602 (2006).

  92. 92.

    Rother, M. A. & Davis, R. H. The effect of slight deformation on droplet coalescence in linear flows. Phys. Fluids 13, 1178–1190 (2001).

  93. 93.

    Voorhees, P. W. The theory of Ostwald ripening. J. Stat. Phys. 38, 231–252 (1985).

  94. 94.

    Taylor, P. Ostwald ripening in emulsions. Adv. Colloid Interface Sci. 75, 107–163 (1998).

  95. 95.

    Lifshitz, I. M. & Slyozov, V. V. The kinetics of precipitation from supersaturated solid solutions. J. Phys. Chem. Solids 19, 35–50 (1961).

  96. 96.

    Roger, K., Olsson, U., Schweins, R. & Cabane, B. Emulsion ripening through molecular exchange at droplet contacts. Angew. Chem. Int. Ed. 54, 1452–1455 (2015).

  97. 97.

    Ficheux, M.-F., Bonakdar, L., Leal-Calderon, F. & Bibette, J. Some stability criteria for double emulsions. Langmuir 14, 2702–2706 (1998).

  98. 98.

    Pays, K., Giermanska-Kahn, J., Pouligny, B., Bibette, J. & Leal-Calderon, F. Double emulsions: How does release occur? J. Control. Rel. 79, 193–205 (2002).

  99. 99.

    Pays, K., Giermanska-Kahn, J., Pouligny, B., Bibette, J. & Leal-Calderon, F. Coalescence in surfactant-stabilized double emulsions. Langmuir 17, 7758–7769 (2001).

  100. 100.

    Jiao, J., Rhodes, D. G. & Burgess, D. J. Multiple emulsion stability: pressure balance and interfacial film strength. J. Colloid Interface Sci. 250, 444–450 (2002).

  101. 101.

    Schmidts, T., Dobler, D., Nissing, C. & Runkel, F. Influence of hydrophilic surfactants on the properties of multiple W/O/W emulsions. J. Colloid Interface Sci. 338, 184–192 (2009).

  102. 102.

    Zeeb, B., Saberi, A. H., Weiss, J. & McClements, D. J. Retention and release of oil-in-water emulsions from filled hydrogel beads composed of calcium alginate: impact of emulsifier type and pH. Soft Matter 11, 2228–2236 (2015).

  103. 103.

    Muschiolik, G. Multiple emulsions for food use. Curr. Opin. Colloid Interface Sci. 12, 213–220 (2007).

  104. 104.

    Sapei, L., Naqvi, M. A. & Rousseau, D. Stability and release properties of double emulsions for food applications. Food Hydrocoll. 27, 316–323 (2012).

  105. 105.

    Kawasaki, J., Kosuge, H., Egashira, R. & Asawa, T. Mechanical entrainment in W/O/W emulsion liquid membrane. Sep. Sci. Technol. 44, 151–168 (2009).

  106. 106.

    Chakraborty, M. & Bart, H.-J. Emulsion liquid membranes: role of internal droplet size distribution on toluene/n-heptane separation. Colloids Surf. A 272, 15–21 (2006).

  107. 107.

    Gupta, S., Chakraborty, M. & Murthy, Z. V. P. Removal of mercury by emulsion liquid membranes: studies on emulsion stability and scale up. J. Dispers. Sci. Technol. 34, 1733–1741 (2013).

  108. 108.

    Hamidi, M., Azadi, A. & Rafiei, P. Hydrogel nanoparticles in drug delivery. Adv. Drug. Deliv. Rev. 60, 1638–1649 (2008).

  109. 109.

    Gawande, M. B. et al. Core–shell nanoparticles: synthesis and applications in catalysis and electrocatalysis. Chem. Soc. Rev. 44, 7540–7590 (2015).

  110. 110.

    Schleich, N. et al. Dual anticancer drug/superparamagnetic iron oxide-loaded PLGA-based nanoparticles for cancer therapy and magnetic resonance imaging. Int. J. Pharm. 447, 94–101 (2013).

  111. 111.

    Matsushita, H. et al. Multifunctional core–shell silica nanoparticles for highly sensitive 19F magnetic resonance imaging. Angew. Chem. Int. Ed. 53, 1008–1011 (2014).

  112. 112.

    Schwarz, J. C. et al. Optimisation of multiple W/O/W nanoemulsions for dermal delivery of aciclovir. Int. J. Pharm. 435, 69–75 (2012).

  113. 113.

    Helgeson, M. E., Moran, S. E., An, H. Z. & Doyle, P. S. Mesoporous organohydrogels from thermogelling photocrosslinkable nanoemulsions. Nat. Mater. 11, 344–352 (2012).

  114. 114.

    An, H. Z., Helgeson, M. E. & Doyle, P. S. Nanoemulsion composite microgels for orthogonal encapsulation and release. Adv. Mater. 24, 3838–3844 (2012).

  115. 115.

    Anton, N., Mojzisova, H., Porcher, E., Benoit, J. & Saulnier, P. Reverse micelle-loaded lipid nano-emulsions: new technology for nano-encapsulation of hydrophilic materials. Int. J. Pharm. 398, 204–209 (2010).

  116. 116.

    Vilanova, N., Kolen’ko, Y. V., Solans, C. & Rodríguez-Abreu, C. Multiple emulsions as soft templates for the synthesis of multifunctional silicone porous particles. J. Colloid Interface Sci. 437, 235–243 (2015).

  117. 117.

    Arriaga, L. R., Amstad, E. & Weitz, D. A. Scalable single-step microfluidic production of single-core double emulsions with ultra-thin shells. Lab Chip 15, 3335–3340 (2015).

  118. 118.

    Abbaspourrad, A., Carroll, N. J., Kim, S.-H. & Weitz, D. A. Polymer microcapsules with programmable active release. J. Am. Chem. Soc. 135, 7744–7750 (2013).

  119. 119.

    Kim, S.-H. et al. Formation of polymersomes with double bilayers templated by quadruple emulsions. Lab Chip 13, 1351–1356 (2013).

  120. 120.

    Hwang, T.-L., Fang, C.-L., Chen, C.-H. & Fang, J.-Y. Permeation enhancer-containing water-in-oil nanoemulsions as carriers for intravesical cisplatin delivery. Pharm. Res. 26, 2314–2323 (2009).

  121. 121.

    de Jonge, N. & Ross, F. M. Electron microscopy of specimens in liquid. Nat. Nanotechnol. 6, 695–704 (2011).

  122. 122.

    Evans, J. E., Jungjohann, K. L., Browning, N. D. & Arslan, I. Controlled growth of nanoparticles from solution with in situ liquid transmission electron microscopy. Nano Lett. 11, 2809–2813 (2011).

  123. 123.

    Yuk, J. M. et al. High-resolution EM of colloidal nanocrystal growth using graphene liquid cells. Science 336, 61–64 (2012).

  124. 124.

    Shum, H. C. et al. Droplet microfluidics for fabrication of non-spherical particles. Macromol. Rapid Commun. 31, 108–118 (2010).

  125. 125.

    Glotzer, S. C. & Solomon, M. J. Anisotropy of building blocks and their assembly into complex structures. Nat. Mater. 6, 557–562 (2007).

Download references

Acknowledgements

T.P. was financially supported by the California Research Alliance by BASF. T.S. and M.E.H. were financially supported by the National Science Foundation under award no. CBET 1351371.

Author information

T.P. researched and prepared the sections on nanoemulsions and multiple nanoemulsions. T.S. researched and prepared the sections on characterizing structure and stability. S.S. researched and prepared the section on applications. M.E.H. prepared the outlook section. All authors revised the manuscript.

Correspondence to Matthew E. Helgeson.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sheth, T., Seshadri, S., Prileszky, T. et al. Multiple nanoemulsions. Nat Rev Mater 5, 214–228 (2020). https://doi.org/10.1038/s41578-019-0161-9

Download citation