Enhanced efficacy, cellular uptake, and antiangiogenic activity of the optimized imatinib mesylate-loaded proniosomal-derived nanovesicles

Abstract

This study was premeditated to elaborate an optimized imatinib mesylate (IM)–loaded proniosomal–derived nanovesicles to investigate its influence on IM effectiveness, cellular uptake, antiangiogenic and autophagic behavior. The influences of drug amount, surfactant and cholesterol ratios, on mean vesicle size (Y1), zeta potential (Y2), along with the percentages of entrapment efficacy (Y3), initial release (Y4), and cumulative release (Y5) were studied and optimized for the prediction of the optimized formula utilizing Box-Behnken design. Differential scanning calorimetry, Fourier-transform infrared, electron, and light microscope were also conducted and confirmed the vesicular formation. Besides, the noteworthy outcomes of the conducted stability study for both the suspension and lyophilized forms of the optimized formula revealed insignificant changes in zeta potential and drug retaining ability, which confirmed the sufficient retained stability over the three-months study period. The in vitro cytotoxicity studies of the optimized formulation revealed IC50 values of 1.5 and 3 folds less than the free drug values in HCT-116 and CaCo2 cell lines, respectively, along with the enhanced cellular uptake by the cancerous cells. The customized release profile of the optimized formulation is assumed to be involved in the improvement of the IM antiangiogenic activity. The autophagic activity was also observed from both the free IM and the optimized formulation. The optimized IM–loaded nanovesicles maximized the stability, efficacy, cellular uptake, and antiangiogenic activity of IM that increase its potential as efficient and promising cancer remediation.