The Immunoenhancement Effects of Polyethylenimine-Modified Chinese Yam Polysaccharide-Encapsulated PLGA Nanoparticles as an Adjuvant

Int J Nanomedicine. 2020 Aug 5:15:5527-5543. doi: 10.2147/IJN.S252515. eCollection 2020.

Abstract

Background: Poly(lactic-co-glycolic acid) (PLGA) has been extensively applied for sustained drug delivery and vaccine delivery system. However, vaccines delivered by PLGA nanoparticles alone could not effectively activate antigen-presenting cells (APCs) to induce strong immune responses.

Purpose: The aim of the present study was to design polyethylenimine (PEI)-modified Chinese yam polysaccharide (CYP)-encapsulated PLGA nanoparticles (CYPP-PEI) as a vaccine delivery system and evaluate the adjuvant activities in vitro and in vivo.

Materials and methods: Cationic-modified nanoparticles exhibited high antigen absorption and could be efficiently taken by APCs to enhance the immune responses. Therefore, PEI-modified CYP-encapsulated PLGA nanoparticles (CYPP-PEI) were prepared. The storage stability and effective adsorption capacity for porcine circovirus-2 (PCV-2) antigen of these antigen-absorbed nanoparticles were measured for one month. Furthermore, the adjuvant activity of CYPP-PEI nanoparticles was evaluated on macrophages in vitro and through immune responses triggered by PCV-2 antigen in vivo.

Results: The PCV-2 absorbed CYPP-PEI nanoparticles showed excellent storage stability and high absorption efficiency of PCV-2 antigen. In vitro, CYPP-PEI nanoparticles promoted antigen uptake, enhanced surface molecular expressions of CD80 and CD86, and improved cytokine secretion of TNF-α, IFN-γ, and IL-12p70 in macrophages. After immunization with CYPP-PEI/PCV-2 formulation in mice, the expressions of surface activation markers on dendritic cells which located in draining lymph nodes were increased, such as MHCI, MHCII, and CD80. In addition, CYPP-PEI nanoparticles induced dramatically high PCV-2-specific IgG levels which could last for a long time and stimulated the secretion of subtype antibodies and cytokines. The results showed that CYPP-PEI could induce Th1/Th2 mixed but Th1-biased type immune responses.

Conclusion: Polyethylenimine-modified Chinese yam polysaccharide-encapsulated PLGA nanoparticle was a potential vaccine delivery system to trigger strong and persistent immune responses.

Keywords: Chinese yam polysaccharide; immune response; macrophages; nanoparticles; poly(lactic-co-glycolic acid); polyethylenimine.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Antigens / immunology
  • Antigens / pharmacology
  • Circovirus / immunology
  • Cytokines / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dioscorea / chemistry*
  • Drug Delivery Systems / methods*
  • Drug Stability
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice, Inbred ICR
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Polyethyleneimine / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Polysaccharides / chemistry*
  • Vaccines / administration & dosage
  • Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Cytokines
  • Polysaccharides
  • Vaccines
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyethyleneimine

Grants and funding

The project was supported by the National Natural Science Foundation of China (Grant No. 31872509, 31672596), the Fundamental Research Funds for the Central Universities (Grant No. KYZ201844), and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). We are grateful to all of the other staff members at the Institute of Traditional Chinese Veterinary Medicine of Nanjing Agricultural University for their assistance in this study.