Synthesis and characterization of rutin-loaded micelles for glioblastoma multiforme treatment: A computational and experimental study

Abstract

The current experiments aimed to develop an anti-glioblastoma multiforme (GBM) formulation based on rutin-loaded nanomicelles. First, the molecular structure of water, and ethanol was constructed using Material Studio software. Then, the structure of the molecules was optimized through the Forcite module in the software. In sequence, to set the temperature of the system the MD simulations were run under the NVT ensemble (constant number of particles, volume, and temperature) with velocity scale as a thermostat and total simulation time equal to 100 ps as the initialization step. We applied the hydrophobic-hydrophobic interactions and micellization process method to encapsulate rutin into micellar nanoparticles. The computational studies showed that in the first 30 ps of the simulation the system is unstable, but after that, the system reached a stable condition. Moreover, we observed that the density of the system rapidly decreased from 0.98 g/cm3 to a stable mean value equal to 0.95 g/cm3. The characterizations using DLS and SEM imaging showed that the synthesized NPs have a size lower than 100 nm. The hemolysis evaluation showed that the Rut-micelles are hemocompatible and induced lower than 10% hemolysis in all tested groups. The highest cell lethality was observed in the group treated with the synthesized Rut-micelles with a concentration of 400μM, which was statistically significant (p < 0.05) to the control and other test groups. The anti-metastatic effect of the Rut-micelles was confirmed via the cell monolayer wound scratch assay. These results illustrated that the synthesized rutin-loaded nanomicelles could be applied as a GBM treatment option to improve the treatment efficiency of glioblastoma multiforme.