Calcite nano-structure as a novel drug carrier for 5-Fluorouracil chemotherapy agent: A computational study using DFT and AIMD

Abstract

Calcium carbonate (${\mathrm{CaCO}}_3$) is regarded as a promising next-generation drug delivery technology owing to its biocompatibility, pH-sensitive properties, nontoxicity, and cost-effectiveness. Calcite, one of the thermodynamically stable anhydrous polymorphic forms of ${\mathrm{CaCO}}_3$, has been utilized in drug delivery systems in various laboratory-based studies. However, no ab initio studies have been conducted on the use of three-dimensional nanostructures of calcite as drug carriers. This work examines a unit cell of calcite as a novel drug delivery system for the chemotherapy drug 5-Fluorouracil (5-FU), utilizing density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations. The results indicate a significant interaction between calcite and 5-FU, with no alterations observed in the molecular geometry. The interaction occurred as a result of charge transfer from the calcite to the molecule. The density of states and absorption spectra of calcite and the 5-FU+calcite complex are studied. The results indicate that calcite exhibits semiconductor characteristics, whereas the complex displays metallic characteristics. In addition, the stability of the complex at human body temperature is investigated using AIMD simulations. The findings indicate that the interaction persists at 310 K and elevated temperatures, with no significant increase in the distance between 5-FU and calcite. The dissolution of calcite in the presence of hydrogen ions ($H^{+}$) ions, indicative of the acidic environment surrounding tumors, facilitates the release of the 5-FU molecule without alterations to its geometry. Ultimately, the results indicate that calcite effectively bonds with 5-FU, maintaining interaction at human body temperature and facilitating release through dissolution in proximity to tumors.