Enhancement of immune responses using ovalbumin-conjugated Eucommia ulmoides leaf polysaccharides encapsulated in a cubic liquid-crystalline phase delivery system

J Sci Food Agric. 2022 Nov;102(14):6757-6770. doi: 10.1002/jsfa.12043. Epub 2022 Jun 16.

Abstract

Background: To improve the adjuvant activity of polysaccharides from Eucommia ulmoides leaves (PsEUL) in inducing an effective immune response against ovalbumin (OVA), PsEUL were conjugated to OVA using the N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) method. The synthesized PsEUL-OVA was encapsulated using phytantriol and F127 to produce PsEUL-OVA cubosomes (Cubs), a novel delivery system. The physicochemical properties and immune modulation effects of this novel delivery system were explored.

Results: In vitro, PsEUL-OVA/Cubs carrying large amounts of OVA were rapidly phagocytized by macrophages and upregulated macrophage proliferation, thereby stimulating cytokine production (interleukin (IL)-6 and IL-4). In vivo, PsEUL-OVA/Cubs increased the titer of OVA-specific antibodies (immunoglobulin (Ig)G, IgG2b, IgG2a and IgG1) and cytokine levels (IL-2, IL-6, IL-4 and interferon-γ). In addition, the cubosomes promoted the differentiation of CD8+ and CD4+ T cells in the spleen and the maturation of dendritic cells (DCs). These results indicated that PsEUL-OVA/Cubs stimulated both cellular and humoral immune responses by enhancing the phagocytic activity of DCs and macrophages and increasing the antigen presentation efficiency.

Conclusion: Collectively, the findings demonstrate that PsEUL-antigen/Cubs can be a useful delivery vehicle with immune response-promoting effects. Therefore, this study lays the foundation for the development of novel adjuvant-antigen delivery systems with potential applications in vaccine design. © 2022 Society of Chemical Industry.

Keywords: cubosomes; delivery system; immune response; polysaccharides from Eucommia ulmoides.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Antigens
  • Cytokines
  • Eucommiaceae*
  • Immunity, Humoral
  • Immunoglobulin G
  • Interferon-gamma
  • Interleukin-2
  • Interleukin-4
  • Interleukin-6
  • Ovalbumin / chemistry
  • Plant Leaves
  • Polysaccharides / chemistry
  • Vaccines*

Substances

  • Adjuvants, Immunologic
  • Antigens
  • Cytokines
  • Immunoglobulin G
  • Interleukin-2
  • Interleukin-6
  • Polysaccharides
  • Vaccines
  • Interleukin-4
  • Interferon-gamma
  • Ovalbumin