Assessment of solvent effects on the inclusion behavior of pyrazinamide drug into cyclic peptide based nanotubes as novel drug delivery vehicles

In the present work, the encapsulation process of Pyrazinamide drug into the cyclic peptide nanotubes with the different numbers of cyclic peptides as novel drug carriers is investigated using density functional theory calculations in the aqueous medium. The negative computed binding energies for all inclusion complexes reveal the stabilization of Pyrazinamide molecule inside the cavities of the nanotubes. Moreover, our computational results indicate that the interaction between Pyrazinamide molecule and the cyclic peptide nanotubes is weak; so that, the drug encapsulation process is typically physisorption. The formation of more number of conventional hydrogen bonds between the Pyrazinamide drug molecule and the active sites of the cyclic peptide nanotube's backbone facilitates the enhancement of binding affinity of the drug molecule into the nanotube with two cyclic peptides and further more stability of the inclusion complex. To characterize the nature of the intermolecular interactions through the topological parameters, the values of electron densities and their Laplacian have been analyzed using the Bader's theory of atoms in molecules. The origin charge transfer during orbital interactions within the encapsulation process of Pyrazinamide drug into cyclic peptide nanotubes is evaluated by the natural bond orbital method. The encapsulation process of Pyrazinamide in the cavity of the nanotubes imparts significant impact on the solvation energy of the drug molecule as well as cyclic peptide nanotubes which introduces the cyclic peptide nanotubes as efficient carriers for delivery of Pyrazinamide drug in nanomedicine domain.