Quantum chemical study of 2-hydroxypropyl-β-cyclodextrin and genipin-crosslinked chitosan nanocarriers functionalized with cytarabine anticancer drug

Abstract

Drug delivery systems based on ring-like nanocarriers such as 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and genipin-crosslinked chitosan (GCS) are increasingly used in the treatment of cancer. The ability of these carriers to deliver the cytarabine anticancer drug (Ara-C) was evaluated. For HP-β-CD and GCS, fifteen (HP-β-CD/Ara-C1-15) and nine (GCS/Ara-C1-9) configurations were optimized at B3LYP/6-31G(d,p) in aqueous solution. The energy of these configurations was also recalculated to account for dispersion correction at M06-2X/6-31G(d,p). The absolute value of the average binding energy for HP-β-CD/Ara-C1-15 was found to be higher than that of GCS/Ara-C1-9. However, these values were higher than 100 kJ mol−1 for both drug delivery systems, indicating that drug loading was acceptable. Quantum molecular descriptors demonstrated that the electronic properties of the drug remained almost unchanged in the HP-β-CD/Ara-C1-15 configurations and the toxicity of the drug was reduced in the GCS/Ara-C1-9 configurations. Quantum theory of atoms in molecules (QTAIM) revealed the essential role of hydrogen bonds in these drug delivery systems.