Properties of Hydrophobized Chitosan-Insulin Nanoparticles with different hydrophobic chain sizes.

E. Robles, E. Villar, J. Juárez, P. Taboada, M.-G. Burboa, M. Alatorre, V. Mosquera, M.-A. Valdez
Universidad de Sonora, MX

Keywords: chitosan, insulin, nanoparticle, ITC, hydrophobic interaction, zeta potential

Summary:

In this work, we investigate the influence of hydrophobization of chitosan on the properties of chitosan-insulin nanoparticles for drug delivery. By a reductive amination method, we use an alkylation procedure to insert 8, 10 and 12 carbons on the chitosan molecule with 5, 10 and 50 % substitution degree along the chain. Infrared and magnetic resonance spectroscopy was used to demonstrate the chitosan–insulin and chitosan-hydrophobic chains interactions. Isothermal titration calorimetry was also used to demonstrate the insulin-hydrophobic chitosan interactions. Dynamic light scattering and zeta potential measurements demonstrated that nanoparticles made with hydrophobic chitosan were smaller and with a higher positive charge than nanoparticles with unmodified chitosan. Transmission and atomic force microscopy observations demonstrated that the influence of hydrophobicity on chitosan and chitosan-insulin nanoparticles was the appearance of more elongated nanoparticles. The influence of pH on the association efficiency and loading capacity of insulin was also investigated. Our results showed that hydrophobic chitosans built nanoparticles with higher association efficiency and higher loading capacity of insulin at pH 6 in comparison with unmodified chitosan. In vitro liberation analysis at pH 5, 6.4 and 7.4 demonstrated that insulin is released more slowly for nanoparticles with hydrophobic chitosans than nanoparticles with unmodified chitosan.