Abstract
The present study reports dual tetanus and diphtheria toxoids loaded stable chitosan–glucomannan nanoassemblies (sCh–GM-NAs) formulated using tandem ionic gelation technique for oral mucosal immunization. The stable, lyophilized sCh–GM-NAs exhibited ~152 nm particle size and ~85% EE of both the toxoids. The lyophilized sCh–GM-NAs displayed excellent stability in biomimetic media and preserved chemical, conformation and biological stability of encapsulated toxoids. The higher intracellular APCs uptake of sCh–GM-NAs was concentration and time dependent which may be attributed to the receptor mediated endocytosis via mannose and glucose receptor. The higher Caco-2 uptake of sCh–GM-NAs was further confirmed by ex vivo intestinal uptake studies. The in vivo evaluation revealed that sCh–GM-NAs posed significantly (p < 0.001) higher humoral, mucosal and cellular immune response than other counterparts by eliciting complete protective levels of anti-TT and anti-DT (~0.1 IU/mL) antibodies. Importantly, commercial ‘Dual antigen’ vaccine administered through oral or intramuscular route was unable to elicit all type of immune response. Conclusively, sCh–GM-NAs could be considered as promising vaccine adjuvant for oral mucosal immunization.
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