Whether carbon nanotubes are suitable for delivering small drugs with aromatic rings through non-covalent adsorption?

Carbon Nanotubes (CNTs) have shown great prospect in the field of biomedicine. CNTs often act as vehi-cles to carry drugs through covalent attachment or noncovalent adsorption, due to their large surface area. Their hollow channels can also accommodate small drugs. However, the drugs may be trapped because of the great potential well of drugs in CNT, which is unfavorable to drug release. Whether CNTs are suitable for delivering small drugs especially those with aromatic rings is still unclear. In this work, we performed molecular dynamics simulations to study the transmembrane transport of drug car-ried by CNTs. Primidone (abbreviated as PRI) was selected as a model small drug, which has two aromatic rings that can interact with CNTs through 7C -7C stacking. Two patterns of drug loading were taken into consideration. One is that drugs are trapped in the CNTs and another is that drugs are adsorbed on outer CNT surface. The two formed CNT-PRI complexes are thermodynamically stable in the water. Potential of mean force calculations show that CNTs have a great potential well to trap PRI molecules, which is not beneficial for PRI release from CNTs into the membrane. When PRI adsorbed on CNT surface, the complex can readily permeate into the membrane. Only after entering the lipid bilayer, can PRI leave the CNT and then diffuse in the membrane. Our results demonstrate that CNT's inner space is not suitable to carry small drugs with aromatic rings, as 7C -7C stacking enhances the trap of drugs in CNT and drugs are hard to leave. However, using CNT outer space to carry and deliver small drugs with aromatic rings is theoret-ically feasible. These findings may provide new insights for the drug delivery using CNTs as vehicles.(c) 2023 Elsevier B.V. All rights reserved.