How do carbon nanotubes serve as carriers for gemcitabine transport in a drug delivery system?

Aiming at understanding the molecular properties of the encapsulation of the anticancer drug gemcitabine in the single-walled carbon nanotube (SWCNT), molecular dynamics (MD) simulations were applied to the two scenarios; that of gemcitabine filling inside the SWCNT, and that of the drug in the free state. Inside the SWCNT, the cytosine ring of gemcitabine was found to form a π–π stacking conformation with the SWCNT surface, and this movement is not along the centerline of the tube from one end to the other of the tube where the distance from the center of gravity of the molecule to the surface is 4.7 Å. A tilted angle of 19° was detected between the cytosine ring of gemcitabine and the inner surface of SWCNT. In comparison to its conformation in the free form, no significant difference was observed on the torsion angle between the five- (ribose) and the six- (cytosine) membered rings. However, gemcitabine inside the SWCNT was found to have a lower number of solvating water molecules but with a stronger net solvation than the drug in the free state. This is due to the collaborative interactions between gemcitabine and the surface of the SWCNT. In addition, the steered molecular dynamics simulation (SMD) approach was employed to investigate the binding free energy for gemcitabine moving from one end to another end throughout the SWCNT. In excellent agreement with that yielded from the classical MD, the SMD energy profile confirms that the drug molecule prefers to locate inside the SWCNT.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (155 K)Download as PowerPoint slideResearch highlightsSince the discovery of carbon nanotubes (CNTs) in 1991, they have been considered as the ideal material for a variety of applications owing to their unique properties. These properties include their potential biocompatibility in pharmaceutical drug delivery systems and their excellent role as drug carriers with a highly site-selective delivery and sensitivity. To accelerate the optimal development of CNT as a new effective drug transporter, it is required to better understand the structural properties of the drug–CNT complex. In this work, the structure, orientation, conformation, solvation and movement of the anticancer drug gemcitabine inside a pristine zigzag (18,0) singlewalled carbon nanotube (SWCNT) in aqueous solution are examined using a molecular dynamics simulation approach. The properties of gemcitabine in the free form (without SWCNT bound) in aqueous solution were also studied and compared. Such information is primarily required in the drug delivery technology in order to bring drug molecule to the specific targets, tumor cells.