Abstract
Chitosan is a natural polysaccharide, mainly derived from the shell of marine organisms. At present, chitosan has been widely used in the field of biomedicine due to its special characteristics of low toxicity, biocompatibility, biodegradation and low immunogenicity. Chitosan nanoparticles can be easily prepared. Chitosan nanoparticles with positive charge can enhance the adhesion of antigens in nasal mucosa and promote its absorption, which is expected to be used for intranasal vaccine delivery. In this study, we prepared chitosan nanoparticles by a gelation method, and modified the chitosan nanoparticles with mannose by hybridization. Bovine serum albumin (BSA) was used as the model antigen for development of an intranasal vaccine. The preparation technology of the chitosan nanoparticle-based intranasal vaccine delivery system was optimized by design of experiment (DoE). The DoE results showed that mannose-modified chitosan nanoparticles (Man-BSA-CS-NPs) had high modification tolerance and the mean particle size and the surface charge with optimized Man-BSA-CS-NPs were 156 nm and +33.5 mV. FTIR and DSC results confirmed the presence of Man in Man-BSA-CS-NPs. The BSA released from Man-BSA-CS-NPs had no irreversible aggregation or degradation. In addition, the analysis of fluorescence spectroscopy of BSA confirmed an appropriate binding constant between CS and BSA in this study, which could improve the stability of BSA. The cell study in vitro demonstrated the low toxicity and biocompatibility of Man-BSA-CS-NPs. Confocal results showed that the Man-modified BSA-FITC-CS-NPs promote the endocytosis and internalization of BSA-FITC in DC2.4 cells. In vivo studies of mice, Man-BSA-CS-NPs intranasally immunized showed a significantly improvement of BSA-specific serum IgG response and the highest level of BSA-specific IgA expression in nasal lavage fluid. Overall, our study provides a promising method to modify BSA-loaded CS-NPs with mannose, which is worthy of further study.
Highlights
A vaccine seems to be the most effective strategy to manage the pandemic of COVID-19 [1,2]
Man has no significant influence on the size/Polydispersity index (PDI)/zeta potential of Man-Bovine Serum Albumin (BSA)-CS nanoparticles (CS-NPs), which indicates a large prescription adjustment range
The optimized Man-BSA-CS-NPs were near-spherical with uniform density and dispersion
Summary
A vaccine seems to be the most effective strategy to manage the pandemic of COVID-19 [1,2]. Amidi et al [26] developed N-trimethyl CS (TMC) NPs loaded with influenza subunit antigen for intranasal vaccination, which had good immunogenicity in a mouse model. It has been reported [27] that the PEGylated CS microspheres loaded with Bordetella bronchiseptica dermonecrotoxin (BBD) antigens were physically more stable and stimulated more cytokines from macrophage cells in vitro as compared to BBD-loaded CS microspheres. In this study, Man-modified CS-NPs were synthesized by a facile ionic gelation method without organi3cofr2e1agents or highly toxic catalysts. IInn aaddddiittiioonn,, TTEEMM mmiiccrrooggrraapphhss ccoonnfifirrmmeedd tthhee nnaannoossiizzee ooff ddrriieedd CCSS--NNPPss,, aanndd tthheetthhiirrddddiimmeennssiioonnaall atathshspaaptetectcththtsesemmddarariyieyedcdcaacucurrsosoesessasa--lslsiminmnkakaelelldldeerrNNddPPiiasasmm((66ee00tte––er22r8o8o0f0fCnCnmSmS--)N)NooPPbbsss.s.eeIIrtrtvvhheeaaddssbabayllyssoToTEbEbMeeMeennhhpapavrvreeeevvaiaioossuummsslalayyllllrereeerrppssooiizrzrteteeedadann[[d3d355a]a] nnaarrrroowweerrssiizzeeddiissttrriibbuuttiioonntthhaanntthheesswwoolllleennNNPPss((227700––337700nnmm))ddeetteecctteeddbbyyDDLLSS
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