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.
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 epsilon-Poly-L-lysine modified PLGA nanoparticles (epsilon PL-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 epsilon PL-AHPP/OVA formulations significantly enhanced lymphocyte proliferation and improved the ratio of CD4+/CD8+ T cells. In addition, AHPP/OVA, PEI-AHPP/OVA and epsilon PL-AHPP/OVA formulations induced secretion of cytokines (TNF-alpha, IFN-gamma, 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.
[1]Nanjing Agr Univ, Coll Vet Med, Inst Tradit Chinese Vet Med, Nanjing 210095, Jiangsu, Peoples R China.
[2]Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Nanjing 210095, Jiangsu, Peoples R China.
[3]Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai 201203, Peoples R China.
(8.0+极速模式)