The development of self-emulsifying oil-in-water emulsion adjuvant and an evaluation of the impact of droplet size on performance

J Pharm Sci. 2015 Apr;104(4):1352-61. doi: 10.1002/jps.24337. Epub 2015 Jan 19.

Abstract

Microfluidization is an established technique for preparing emulsion adjuvant formulations for use in vaccines. Although this technique reproducibly yields high-quality stable emulsions, it is complex, expensive, and requires proprietary equipment. For this study, we developed a novel and simple low shear process to prepare stable reproducible emulsions without the use of any proprietary equipment. We found this process can produce a wide range of differently sized emulsions based on the modification of ratios of oil and surfactants. Using this process, we prepared a novel 20-nm-sized emulsion that was stable, reproducible, and showed adjuvant effects. During evaluation of this emulsion, we studied a range of emulsions with the same composition all sized below 200; 20, 90, and 160 nm in vivo and established a correlation between adjuvant size and immune responses. Our studies indicate that 160-nm-sized emulsions generate the strongest immune responses.

Keywords: emulsion; formulation; particle size; physical characterization; self-emulsifying; squalene; vaccine adjuvants; vaccines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Antibodies / blood
  • Biomarkers / blood
  • Cells, Cultured
  • Chemistry, Pharmaceutical
  • Emulsions
  • Female
  • Immunity, Humoral / drug effects
  • Immunization
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / chemistry
  • Influenza Vaccines / immunology*
  • Injections, Intramuscular
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microfluidics
  • Nanoparticles
  • Oils / administration & dosage
  • Oils / chemistry
  • Oils / pharmacology*
  • Ovalbumin / administration & dosage
  • Ovalbumin / chemistry
  • Ovalbumin / immunology*
  • Particle Size
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Technology, Pharmaceutical / methods
  • Time Factors
  • Water / administration & dosage
  • Water / chemistry
  • Water / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Antibodies
  • Biomarkers
  • Emulsions
  • Influenza Vaccines
  • Oils
  • Water
  • Ovalbumin