Cationic polymer modified PLGA nanoparticles encapsulating Alhagi honey polysaccharides as a vaccine delivery system for ovalbumin to improve immune responses

Abstract

Adelijiang Wusiman,1,2 Pengfei Gu,1,2 Zhenguang Liu,1,2 Shuwen Xu,1,2 Yue Zhang,1,2 Yuanliang Hu,1,2 Jiaguo Liu,1,2 Deyun Wang,1,2 Xiaoyan Huang31Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine; 2MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, People’s Republic of China; 3Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of ChinaBackground: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and surface modified PLGA nanoparticles have been widely studied as antigens or drugs carriers due to their controlled release characteristics and biocompatibility. However, most PLGA nanoparticles have lower antigens loading efficiency and adjuvanticity.Purpose: The aim of this study was to improve the antigen loading efficiency and adjuvant activity of PLGA nanoparticles.Materials and methods: Surface cationic polymer modification can improve the antigens loading efficiency of PLGA nanoparticles by surface adsorption. Therefore, in this study, chitosan modified PLGA nanoparticles (CS-AHPP/OVA), polyethyleneimine modified PLGA nanoparticles (PEI-AHPP/OVA), and ϵ-Poly-L-lysine modified PLGA nanoparticles (ϵPL-AHPP/OVA) were prepared as antigen delivery carriers to investigate the characterization and stability of these nanoparticles. These nanoparticles were evaluated for their efficacies as adjuvants pre- and post-modification.Results: The AHP and OVA-loaded PLGA nanoparticles (AHPP/OVA) were positively charged after surface cationic polymers modification, and their structural integrity was maintained. Their antigen loading capacity and stability of nanoparticles were improved by the surface cationic polymers modification. Increased positive surface charge resulted in greater OVA adsorption capacity. Among AHPP/OVA and the three surface cationic polymers synthesized from modified PLGA nanoparticles, PEI-AHPP/OVA showed the highest antigen loading efficiency and good stability. AHPP/OVA, CS-AHPP/OVA PEI-AHPP/OVA, and ϵPL-AHPP/OVA formulations significantly enhanced lymphocyte proliferation and improved the ratio of CD4+/CD8+ T cells. In addition, AHPP/OVA, PEI-AHPP/OVA and ϵPL-AHPP/OVA formulations induced secretion of cytokines (TNF-α, IFN-γ, IL-4, and IL-6), antibodies (IgG) and antibody subtypes (IgG1 and IgG2a) in immunized mice. These results demonstrate that these formulations generated a strong Th1-biased immune response. Among them, PEI-AHPP/OVA induced the strongest Th1-biased immune response.Conclusion: In conclusion, PEI-AHPP/OVA nanoparticles may be a potential antigen delivery system for the induction of strong immune responses.Keywords: Alhagi honey polysaccharides, cationic polymer, poly(lactic-co-glycolic acid), nanoparticles, OVA

Keywords

• Alhagi honey polysaccharides
• Cationic polymer
• Poly(lactic-co-glycolic acid)
• Nanoparticles
• OVA