title: The development of self-emulsifying oil-in-water emulsion adjuvant and an evaluation of the impact of droplet size on performance.
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.
authors.affiliation: Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, 02115.
authors.forename: Ruchi R
authors.initials: RR
authors.lastname: Shah
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dodd
authors.forename: Mary
authors.initials: M
authors.lastname: Schaefer
authors.forename: Mildred
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Gillis R
authors.initials: GR
authors.lastname: Otten
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
authors.forename: Luis A
authors.initials: LA
authors.lastname: Brito
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004655:Emulsions; D005260:Female; D056724:Immunity, Humoral / Q000187:drug effects; D007114:Immunization; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D007273:Injections, Intramuscular; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D044085:Microfluidics; D053758:Nanoparticles; D009821:Oils / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D010316:Particle Size; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014867:Water / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D015415:Biomarkers; D004655:Emulsions; D007252:Influenza Vaccines; D009821:Oils; D014867:Water; D010047:Ovalbumin
keywords: emulsion; formulation; particle size; physical characterization; self-emulsifying; squalene; vaccine adjuvants; vaccines