Preparation of Modified Konjac Glucomannan Nanoparticles and their Application as Vaccine Adjuvants to Promote Ovalbumin-Induced Immune Response in Mice

Pharm Res. 2018 Mar 20;35(5):105. doi: 10.1007/s11095-018-2381-x.

Abstract

Purpose: Herein, we reported a facile strategy for synthesis of two types of modified konjac glucomannan nanoparticles (NPs). The goal of this project was to explore the potential of the NPs as vaccine adjuvants.

Methods: Firstly, anionic carboxymethylated konjac glucomannan (CKGM) and cationic quaternized konjac glucomannan (QKGM) were synthesized by chemical modification of konjac glucomannan (KGM). Subsequently, two types of NPs, CKGM/QKGM and sodium tripolyphosphate (TPP)/QKGM, were prepared through polyelectrolyte complex method and ionic cross-linking method, respectively. The thus-synthesized NPs were then loaded with ovalbumin (OVA) to further evaluate the effect of NPs on immune response in mice.

Results: The encapsulation efficiency of OVA for CKGM/QKGM/OVA and TPP/QKGM/OVA NPs could be 49.2% and 67.7%, respectively, while the drug loading capacity could reach 10.9% and 60%. The NPs showed irregular spherical shape and exhibited good sustained-release properties. In vitro cytotoxicity assay revealed that both the blank and OVA-loaded NPs were not toxic to cells. The OVA-specific IgG, splenocytes proliferation and cytokine levels indicated that the OVA-induced humoral and cellular immune responses were up-regulated by OVA-loaded NPs. What's more, CKGM/QKGM/OVA NPs elicited both higher IL-2 and IFN-γ production, while TPP/QKGM/OVA NPs elicited both higher IL-4 and IL-10 production.

Conclusions: These results suggest that TPP/QKGM and CKGM/QKGM NPs are promising to be used as vaccine adjuvants. The TPP/QKGM/OVA NPs could induce stronger humoral immune response, while CKGM/QKGM/OVA NPs could enhance the cellular immune response more effectively.

Keywords: chemical modification; immune response; konjac glucomannan; nanoparticles; vaccine adjuvants.

MeSH terms

  • Adjuvants, Immunologic / chemistry*
  • Animals
  • Drug Compounding / methods
  • Female
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Immunogenicity, Vaccine
  • Mannans / chemistry*
  • Mannans / immunology
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Nanoparticles / chemistry*
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Vaccines / administration & dosage
  • Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Mannans
  • Vaccines
  • (1-6)-alpha-glucomannan
  • Ovalbumin