Adjuvant Activity of PLA Microspheres Regulated by Protamine Sulfate
LIU Yu-ying CHEN Xiao-ming WANG Lian-yan, YUAN Qi-peng MA Guang-hui
Key Laboratory of Bioprocess of Beijing, Beijing University of Chemical Technology Institute of Process Engineering, Chinese Academy of Sciences . State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences School of Life Science and Technology, Beijing University of Chemical Technology State Key Lab. Biochem. Eng., Inst. Process Eng., Chinese Academy of Sciences
Abstract:Polylactic acid (PLA) microspheres and protamine sulfate (PS) modified PLA microspheres were prepared with ethyl acetate (for 400 nm diameter) or dichloromethane (for 900 nm diameter) by premix membrane emulsification method. BALB/c mice were used to evaluate the adjuvanticity of as-prepared microparticles for HBsAg, and the effect of particles size on their adjuvanticity was investigated. The results indicated that PS modification significantly promoted the adsorption of HBsAg onto the microspheres, and the adsorption rate was increased to 8.16% from 2.07%. Compared with PLA microspheres, PS modified microspheres induced more potent immune response, the spot formation cells (SFCs) of IL-2 and IFN-g (Th1 type cytokine) were increased 261% and 139%, respectively. The SFCs of IL-4 secretion of Th2 type cytokine were also enhanced by 67%. Immune effect of different sizes of PLA-PS microspheres demonstrated that the secretion level of IL-2 for 400 nm microspheres was 1.68 times to the counterparts of 900 nm microspheres.
Key words: polylactic acid microsphere; protamine sulfate; adjuvant; membrane emulsification