Preparation, Evaluation and Optimization of Nanoparticles Composed of Thiolated Triethyl Chitosan: A Potential Approach for Buccal Delivery of Insulin Publisher



Rahbarian M¹ ; Mortazavian E¹ ; Dorkoosh FA¹ ; Rafiee Tehrani M¹ Show Affiliations
Source: Journal of Drug Delivery Science and Technology Published:2018

Abstract

In the present work, insulin nanoparticles composed of thiolated N-triethyl chitosan (TEC-Cys), as a new derivative, were synthesized and characterized by the 1H-NMR. Triethyl chitosan (TEC) was thiolated with L-Cysteine (Cys) by the formation of an amide bond between the residual primary amino group of quaternized chitosan and carboxylic group of Cys. Then, the nanoparticles were prepared by the polyelectrolyte complexation (PEC) method. The preparation of the nanoparticles was optimized using the Box-Behnken experimental design methodology. The independent factors were pH of the polymer solution, a concentration ratio of polymer/insulin and stirring rate, while the dependent factors were size, poly dispersity index (PdI), zeta potential and entrapment efficiency (EE%). The values of 126.9 nm, 0.26, 24.6 mV and 97.8% for the particle size, PdI, zeta potential and EE%, respectively, showed proper physicochemical properties for the TEC-Cys nanoparticles (19% degree of quaternization and 165 μmole thiol group/gram of polymer). Furthermore, the morphology of the nanoparticles was studied using scanning electron microscopy (SEM), which revealed separate, spherical, and non-aggregated nanoparticles. The in vitro release of insulin from the nanoparticles was carried out in phosphate buffer solution (PBS) with pH = 7.4 and showed 98% drug release within 480 min. Finally, the permeability of the insulin nanoparticles was done through rabbit buccal mucosa as an ex vivo study and represented that the permeability of insulin can reach 96% in 480 min. Tissue viability was assessed using a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) biochemical assay and showed no significant cytotoxic effect for rabbit buccal mucosa. According to our results, the TEC-Cys nanoparticulate system can be a good approach for buccal delivery of insulin. © 2017 Elsevier B.V.