Preparation, design for optimization and in vitro evaluation of insulin nanoparticles integrating thiolated chitosan derivatives

This study aims at the statistical optimization and in vitro characterization of insulin nanoparticles containing thiolatd N-diethyl methyl chitosan (DEMC-Cys) and N-dimethyl ethyl chitosan (DMEC-Cys) conjugates. Insulin nanoparticles containing these conjugates were prepared by polyelectrolyte complexation (PEG) method. Further optimization of nanoparticles was continued by Box-Behnken design. Morphological studies of optimized nanopaticles were performed by scanning electron microscopy (SEM). In vitro release study was carried out in phosphate buffer solution pH 6.8. Insulin nanoparticles composed of DMEC-Cys (35 % degree of quaternization and 155 mu mole thiol group/gram polymer) had more effect on minimizing particle size of insulin nanoparticles compared to DEMC-Cys (12 % degree of quaternization and 165 mu mole thiol group/gram polymer). Optimized nanoparticles were shown to have mean particle size diameter of 174 nm, zeta potential of 24.04 mV. PdI of 0.196 and EE of 98.35 %. In vitro release study of the optimized nanoparticles showed 71.29 % within 240 min.