Characterization of drug–chitosan interaction by 1H NMR, FTIR and isothermal titration calorimetry

Electrostatic interaction between opposite charge of drugs (insulin and benzoic acid) and chitosan was studied by 1H NMR, FTIR and isothermal titration calorimetry (ITC). No ionic interaction between the carboxyl group of benzoic acid and the amine group of chitosan could be detected. There was a minor change in the FTIR spectra of insulin–chitosan microparticles made of different concentrations of insulin. Exothermic heat of reaction between insulin and chitosan was obtained by ITC. However, the measured interaction enthalpy change (ΔH) was possibly due to the conformational changes and the adsorption phenomena of insulin onto the surfaces of the particles but not to a binding interaction. The binding of tripolyphosphate, a widely used cross-linking agent, to pH 3.3 and pH 5 chitosan was also studied by ITC. The interaction enthalpy change of the binding between tripolyphosphate and chitosan indicated that tripolyphosphate provided a stronger interaction to pH 5 chitosan than to pH 3.3 chitosan. However, it can be stated that the electrostatical interaction forces between the tested molecules insulin, benzoic acid, and tripolyphosphate and chitosan are found to be very weak.