DFT insights into heteroatom-doped C60 nanocages as potential drug carriers for lorazepam

Abstract

Efficient delivery of lorazepam remains challenging due to its poor aqueous solubility, limited bioavailability, and delayed onset of action. In this work, a density functional theory (DFT) study was conducted to investigate the adsorption behavior of lorazepam on pristine C₆₀, SiC₅₉, and GeC₅₉ nanostructures as potential drug delivery systems. Various adsorption configurations were optimized to identify the most stable binding modes and interaction mechanisms. The calculated adsorption energies indicate that C₆₀ exhibits relatively weaker interactions compared to doped systems, while silicon and germanium doping significantly enhance the adsorption strength. In particular, the SiC₅₉ system shows the highest stability, with adsorption energies reaching approximately −6.1 eV, indicating strong binding suitable for drug loading applications. GeC₅₉ also demonstrates enhanced adsorption compared to C₆₀, although weaker than Si doping. Several analytical tools were employed, including reduced density gradient (RDG–NCI) analysis, partial density of states (PDOS), natural bond orbital (NBO) analysis, infrared (IR) spectroscopy, work function (φ), and HOMO–LUMO gap, which confirm significant electronic interaction and charge transfer between the drug and nanocarrier. Solvent effects further reveal that adsorption remains energetically favorable in aqueous environments. Importantly, protonation studies under acidic conditions demonstrate a significant weakening of the interaction, confirming the feasibility of a pH-responsive drug release mechanism. Overall, these findings highlight doped C₆₀ nanocages, especially SiC₅₉, as promising candidates for efficient and controlled lorazepam delivery.