Replica exchange molecular dynamics simulation of chitosan for drug delivery system based on carbon nanotube

Chitosan is an important biopolymer in the medical applications because of its excellent biocompatibility. It has been recently highlighted in the targeted drug delivery system (DDS) by improvement of the carbon nanotube (CNT) solubility. To investigate the effect of chitosan length, the two targeted DDSs with 30 and 60 chitosan monomers were performed by replica-exchange molecular dynamics simulations at temperatures in the range of 300–455 K with three different combinations of force fields and implicit solvation models. Each DDS model contains the epidermal growth factor (EGF), chitosan (CS) of 30 (30CS) and 60 (60CS) monomers, single-wall CNT (SWCNT) and gemcitabine (Gemzar) as the model payload anticancer drug, called EGF/30CS/SWCNT/Gemzar and EGF/60CS/SWCNT/Gemzar, respectively. The SWCNT confines gemcitabine inside its cavity, while the outer surface is wrapped by chitosan in which one end is linked to the EGF. Even though the REMD results from different force fields and implicit solvation models are not exactly identical, all of them are in the same trend confirming that in the EGF/30CS/SWCNT/Gemzar DDS the 30CS chain was not long enough to wrap around the SWCNT, and consequently the EGF was located so close to the tube as to potentially cause steric inhibition of the binding of EGF to its receptor (EGFR), which is highly expressed on the surface of cancer cells. On the other hand, this phenomenon is not observed in the EGF/60CS/SWCNT/Gemzar DDS in which the 60CS was found to completely wrap over the CNT outer surface using only 50 chitosan units. The evidence suggested that a ratio of chitosan molecular weight per SWCNT surface area larger than 9.9 × 10−7 kg/m2 is suitable for application in targeted DDSs. Although an increase in the temperature is likely to influence the overall DDS structure, and especially the orbit of helical chitosan on the SWCNT and the EGF conformation, gemcitabine is still encapsulated inside the tube.

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► The behaviors of wrapped chitosan chain over SWCNT surface depend on temperature.
► The length of chitosan effect to the binding of EGF and it receptor (EGFR).
► A ratio of chitosan MW per SWCNT surface area suitable for targeted DDS is exposed.