Development of novel cationic microemulsion as parenteral adjuvant for influenza vaccine  

作　　者：Sakalanunt Lamaisakul Angkana Tantituvanont Vimolmas Lipipun Garnpimol Ritthidej 

机构地区：[1]Department of Pharmaceutics and Industrial Pharmacy,Faculty of Pharmaceutical Sciences,Chulalongkorn University,Bangkok 10330,Thailand [2]Department of Biochemistry and Microbiology,Faculty of Pharmaceutical Sciences,Chulalongkorn University,Bangkok 10330,Thailand

出　　处：《Asian Journal of Pharmaceutical Sciences》2020年第5期591-604,共14页亚洲药物制剂科学（英文）

基　　金：Research grant from the Office of Higher Education Commission via Chulalongkorn University,the fiscal year 2014–2015 is acknowledged。

摘　　要：Squalene-based oil-in-water(O/W)emulsions have been used as effective and safe adjuvants in approved influenza vaccines.However,there are concerns regarding the safety and side effects of increasing risk of narcolepsy.In present study,novel O/W microemulsions(MEs)containing wheat germ oil,D-alpha tocopheryl polyethylene glycol 1000 succinate(TPGS)and Cremophor EL(CreEL)or Solutol HS15 were formulated with/without a cationic surfactant,cetyltrimethylammonium bromide(CTAB)and then sterilized by autoclaving.Their physical properties and biological efficacies were evaluated.The results demonstrated that autoclaving reduced the droplet size to^20 nm with narrow size distributions resulting in monodisperse systems with good stability up to 3 years.Hemolytic activity,viscosity,pH,and osmolality were appropriate for parenteral use.Bovine serum albumin(BSA),a model antigen,after mixing with MEs retained the protein integrity,assessed by SDS-PAGE and CD spectroscopy.Greater percentages of 28 SC cell viability were observed from CreEL-based MEs.Uptake of FITC-BSA-MEs increased with the increasing concentration of CTAB confirmed by CLSM images.Furthermore,cationic CreEL-based MEs could induce Th1 cytokine synthesis with an increase in TNF-α and IL-12 levels and a decrease in IL-10 level.In vivo immunization study in mice of adjuvants admixed with influenza virus solution revealed that nonionic and selected cationic CreEL-MEs enhanced immune responses as measured by influenza-specific serum antibody titers and hemagglutination inhibition titers.Particularly,cationic CreEL-based ME showed better humoral and cellular immunity with higher IgG2 a titer than nonionic CreEL-based ME and antigen alone.No differences in immune responses were observed between mice immunized with selected cationic CreEL-based ME and marketed adjuvant.In addition,the selected ME induced antigen-sparing while retained immune stimulating effects compared to antigen alone.No inflammatory change in muscle fiber structure was observed.Accordingly,the develo

关 键 词：Cationic microemulsion ADJUVANT Influenza virus VACCINE 

分 类 号：R943[医药卫生—药剂学]