Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and carbon nanotubes) to assess drug delivery to the CNS: a molecular docking study

S. Shityakov, C. Förster
University of Würzburg, DE

Keywords: nanoparticles, drug delivery, CNS


P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain chemical balance in the central nervous system (CNS) for endogenous and exogenous chemical compounds. However, despite the extensive characterization of P-gp potential interaction with drug-like molecules, the mechanism of nanoparticles is poorly understood. Thus in the present study we analyzed nanoparticles, such as buckminsterfullerenes (C20, C60, C70), capped single-walled carbon nanotube (SWCT, C168), and P-gp interactions using molecular docking technique based on the molecular shape and hydrophobic forces to estimate the binding affinities between these structures. The theoretical results represented in this work show that the hydrophobic residues of P-gp interact with lipophilic lattices of nanoparticles (π-π-stacking), and provide the possible evidence for their substrate or inhibitor specificity/non-specificity for P-gp. Further, the obtained data draw the conclusion that nanocapsules, such as SWCN might be promising drug delivery vehicles to administer and assess drug-like chemical compound to the CNS, since organisms have not evolved evolutionary to detect this type of nanostructures.