Enhance the efficiency of 5-fluorouracil targeted delivery by using a prodrug approach as a novel strategy for prolonged circulation time and improved permeation

Publication date: Available online 2 July 2019Source: International Journal of PharmaceuticsAuthor(s): Samaneh Pasban, Heidar Raissi, Majid Pakdel, Farzaneh FarzadAbstractDue to the toxicity and resistance to treatment with anticancer drugs, various methods are used to improve their efficacy in cancer treatment. In this present study, in order to overcome the limitation of 5-Fluorouracil (5-FU), prodrug strategy has been pursued with using density functional theory (DFT) and molecular dynamics simulation (MDs). The main objective of this study is to examine the mechanisms of drug release from its prodrug form by using the intrinsic reaction coordinate (IRC) calculations. The reaction mechanisms of 5-FU prodrug (EMC-5-FU) in the presence of lactic acid (LA) and water molecule were theoretically studied. The IRC calculations were carried out at the M06-2X/6-311G** level in the aqueous phase through the mechanism of ester hydrolysis to obtain energies, the geometry optimization of all stationary points along the potential energy surfaces (PES), and also to determine the harmonic vibrational frequencies. The results herein presented suggest that three reaction pathways and transition states TS1 to TS2 are involved along the calculated potential energy surface. We found that the drug molecule is released in the third step and this occurs by separation CH2O group in the presence of water molecule with the highest energy barrier about 25.9 kcal/mol. Since the carbon nanotubes (CNTs)...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research