Encapsulation and Release of Drug Molecule Pregabalin Based on Ultrashort Single-Walled Carbon Nanotubes

Carbon nanotubes (CNTs) have been regarded as one of the most hopeful candidates for transporting drugs to target cells because of their huge surface area, hollow structure, and enhanced cellular uptake. The idea of using their hollow channels as containers to load and unload small drug molecules has been proposed for many years. However, the encapsulation of drugs into CNTs, the internalization of CNT-drug conjugates in the cell membrane, and the successive drug release at the atomic level remain unclear. In this work, we performed molecular dynamics simulations to investigate the potential application of CNTs as a nanocarrier to transport and deliver drug molecules. Pregabalin (PRE) was selected as a model drug, as its size and polarity are suitable for transporting through CNT hollow channels. The simulation can be divided into three stages. First, PRE was encapsulated into the optimized CNT in the water solution and the PRE–CNT complex was formed, then this complex readily entered the lipid bilayer and finally PRE released one by one from CNTs into the membrane. Compared with the direct insertion of PRE in the membrane, the PRE–CNT complex can reduce the energy barrier to enter the membrane and pass the bilayer center. The fast release of PRE from CNTs benefits from its amphipathicity. The electrostatic interaction between its polar groups and lipid headgroups pull the PRE molecules out of the CNT. The results indicate that both the loading and unloading of PRE based on CNTs are energetically favorable. CNTs exhibit great potential as nanovehicles to carry and deliver particular drug molecules