Immunoenhancement effects of chitosan-modified ginseng stem-leaf saponins-encapsulated cubosomes as an ajuvant

Abstract

Nanoparticle delivery of functional molecules and vaccine is a promising method for enhancing the immune response. The objective of this study was to design chitosan (CS)-modified ginseng stem-leaf saponins (GSLS)-encapsulated cubosomes (Cub-GSLS^CS) as a vaccine delivery system and explore its immunologic activity and adjuvanticity. In this study, CS-modified GSLS-encapsulated cubosomes (Cub-GSLS^CS) were prepared. The storage stability of GSLS and that of ovalbumin (OVA) were measured. Additionally, the immunopotentiation of Cub-GSLS^CS were assessed on potentiating macrophage in vitro, and the adjuvant activity was evaluated through immune response triggered by OVA model antigen. The encapsulation efficiency of optimized Cub-GSLS^CS was about 65 % with Im3m nanostructure. The Cub-GSLS^CS showed excellent stability and sustained release for up to 28 days. In vitro, Cub-GSLS^CS nanoparticles improved cellular uptake, stimulated cytokines secretion of IL-6, IL-12, TNF-α, and generated more inducible nitric oxide synthase (iNOS) to produce higher levels of nitric oxide (NO) compared with other groups. Furthermore, the immunoadjuvant effects of OVA encapsulated Cub-GSLSCS nanoparticles (Cub-GSLS^CS-OVA) were observed through immunized mice. Results showed that the ratio of CD4+/CD8 + T lymphocytes was increased in Cub-GSLS^CS-OVA group. In addition, Cub-GSLS^CS-OVA nanoparticles induced dramatically high OVA-specific IgG, IgG1, and IgG2a levels and stimulated the secretion of cytokines. Cub-GSLS^CS may be a potential vaccine delivery system and induce a long-term sustained immunogenicity.

Keywords: Adjuvant; Chitosan; Cubosomes; Ginseng stem-leaf saponins; Macrophage.