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

阳离子聚合物修饰的 PLGA 纳米粒子包覆骆驼蜂多糖,作为卵清蛋白的疫苗输送系统,以改善免疫反应

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作者:Adelijiang Wusiman, Pengfei Gu, Zhenguang Liu, Shuwen Xu, Yue Zhang, Yuanliang Hu, Jiaguo Liu, Deyun Wang, Xiaoyan Huang

Background

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.

Conclusion

In conclusion, PEI-AHPP/OVA nanoparticles may be a potential antigen delivery system for the induction of strong immune responses.

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.

Purpose

The aim of this study was to improve the antigen loading efficiency and adjuvant activity of PLGA nanoparticles. Materials and

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.

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