Journal
PHARMACEUTICAL RESEARCH
Volume 35, Issue 5, Pages -Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-018-2381-x
Keywords
chemical modification; immune response; konjac glucomannan; nanoparticles; vaccine adjuvants
Funding
- Da BeiNong Group Promoted Project for Young Scholar of HZAU [2017DBN010]
- State Key Laboratory of Agricultural Microbiology [AMLKF201507]
- National Natural Science Foundation of China [21503085]
- Natural Science Foundation of Hubei Province [2015CFB233]
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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 complexmethod 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-gamma 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.
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