Modeling and optimization of the niosome nanovesicles using response surface methodology for delivery of insulin

Abstract

Niosome is a drug carrier with high stability and biocompatibility that provides higher drug availability, which results in improved therapeutic performance. Despite some promises that show the potential of using niosome for oral delivery of insulin, the effect of multiple factors such as the concentration of the ingredients, mechanical forces, and experimental conditions on final products make the synthesis of insulin-loaded niosomal particle with the proper characteristics very challenging. In this study, the effects of different factors including the concentration of cholesterol and surfactant, as well as duration of sonication, on zeta-potential, polydispersity index (PDI), and entrapment efficiency (EE%) of the insulin-loaded niosomal vesicles were evaluated and optimum condition was assessed in terms of cytocompatibility and in vitro drug release. The results show that the cholesterol concentration and sonication time have a significant influence on the zeta-potential, whereas the surfactant concentration plays no role. In addition, PDI increased with an increase in cholesterol and surfactant concentration but decreased with increase in the duration of sonication. Furthermore, increasing cholesterol concentration increased EE and increasing the duration of sonication decreased EE. Considering the effect of different factors, the optimum condition, which is defined as minimum PDI, maximum EE, and zeta potential >±30 mV, occurred while the concentration of the cholesterol and surfactant was 1 M and sonication time was 10 min. The zeta potential, PDI, and EE of the optimum insulin-loaded niosomal vesicles were 36.23 ± 1.04 mV, 0.53 ± 0.07 and 79 ± 2%, which were very close to the predicted values, with the prediction error below 5%. Finally, the optimum insulin-loaded niosomal vesicles were characterized in different aspects. They displayed a spherical morphology with a low tendency to be aggregated. In addition, they showed good biocompatibility with Caco-2 cells and slow release in simulated intestinal fluid.