Chitosan nanocomposite drug delivery systems designed for the ifosfamide anticancer drug using molecular dynamics simulations

Abstract

The capacity of chitosan (CS) nanocomposite systems containing graphene (G), N-doped graphene (GN) or P-doped graphene (GP) nanoparticles for the delivery of ifosfamide (IF) anticancer drug was examined by means of molecular dynamics (MD) simulations in order to find the most suitable drug delivery system (DDS). Moreover, the effect of temperature on the characteristics of these systems was investigated by running the MD simulations at four temperatures (298.15, 308.15, 318.15 and 328.15 K). The free volume (FV) and fractional free volume (FFV) values were increased by raising the temperature and the greatest FV and FFV were measured for the CS-GN-IF at 328.15 K equal to 11,751.73 Å3 and 40.9112%, respectively. The FV and FFV were changed in the order of CS-GN-IF > CS-GP-IF > CS-G-IF. The inter-chain distances at 328.15 K for the CS-G-IF, CS-GN-IF and CS-GP-IF were 0.9873, 0.8292 and 0.8856 Å, respectively, confirming the greatest intermolecular interactions in the CS-GN-IF due to formation of strong as well as weak hydrogen bonds among the polymer chains, GN NPs as well as IF molecules. The mean square displacement (MSD) and diffusion coefficient were enhanced by increasing the temperature. The greatest diffusion coefficient at 328.15 K (0.0693 × 10−5 cm2/s) was achieved for the CS-G-IF, a medium value was measured for the CS-GP-IF (0.0613 × 10−5 cm2/s) and the CS-GN-IF revealed the lowest diffusion coefficient (0.0565 × 10−5 cm2/s) approving the diffusion of drug in the CS-GN-IF was happened in the most controlled manner leading to the most efficient drug delivery.