Oral Methylated N-Aryl Chitosan Derivatives for Inducing Immune Responses to Ovalbumin
AbstractPurpose: To investigate different structures of modified chitosan containing different chain lengths and aromatic moieties for vaccine delivery capacity.
Methods: The characteristics of the modified chitosan, namely, methylated N-(4-N,Ndimethylaminobenzyl) chitosan (TM-Bz-CS), methylated N-(4-N,N-dimethylaminocinnamyl) chitosan (TM-CM-CS) and methylated N-(4-pyridinylmethyl) chitosan (TM-Py-CS), with Eqiva degree (equivalent
degree) were studied by in vitro absorption enhancement on the transepithelial electrical resistance (TEER) in Caco-2 cell monolayers as well as by in vivo adjuvant activity against ovalbumin (OVA), a model antigen, via oral administration to BALB/c mice.
Results: At the same concentration and pH (0.1 mg/ml, pH 7.4), TM65CM50CS exhibited the highest in vitro enhancing paracellular permeability and also the highest in vivo adjuvant activity following oral
administration to mice. OVA-specific serum immunoglobulin G (IgG) antibody levels of mice that received OVA in TM65CM50CS were significantly (p < 0.05) higher than those that received OVA in
TM65CS, TM56Bz42CS and TM53Py40CS. On the other hand, TM65CS and TM56Bz42CS exhibited in vitro enhancing paracellular permeability but showed no immune responses, while TM53Py40CS failed to enhance paracellular permeability and did not elicit immune responses as well.
Conclusion: This study demonstrates that addition of hydrophobic moiety (dimethylaminocinnamyl) to CS backbone can increase both its absorption enhancing property and adjuvant activity. The chemical structure and the positive charge location play an important role for binding affinity, absorption enhancement and immune responses.
Keywords: Chitosan derivatives; Absorption enhancement; Oral vaccine delivery; Immunoadjuvants; Ovalbumin.
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