Phosphate functionalized (4,4)-armchair CNTs as novel drug delivery systems for alendronate and etidronate anti-osteoporosis drugs.

The ability of (4,4)-armchair CNT and its three phosphate functionalized forms (CNT-nHPO, n=1-3) were evaluated as novel drug delivery systems (DDSs) for the two commercially well-known anti-osteoporosis drugs namely alendronate (AL) and etidronate (ET). For this purpose, the DFT calculations were accomplished at both B3LYP and B3PW91 levels using 6-31g(d) basis set. The binding energy was increased by increasing number of HPO moieties attached on the CNT with the most negative binding energy was measured for the carrier containing three phosphate groups. The dipole moments of all phosphate containing CNTs were much greater (∼2.2-4.4D) than that of pristine CNT (∼0D). The contour maps proved that when the CNT was functionalized by HPO groups, the symmetric distribution of electric charge was vanished with the charge distribution was the highest asymmetric for the CNT-2HPO while it was the lowest asymmetric for CNT-3HPO leading to the greatest dipole moment for the CNT-2HPO (4.177D) while the smallest dipole moment for the CNT-3HPO (1.614D). Among all compounds, those containing the CNT-3HPO exhibited the smallest band gap energy, chemical potential and hardness but the greatest electronegativity and electrophilicity index which were all suitable and effective for the attachment of drugs onto the bone surface (having partial positive charge due to the presence of Ca as CaCO) and therefore inhibiting the osteoporosis. Consequently, it was established that the drug-CNT-3HPO was the most appropriate drug-carrier compound for both of the AL and ET drugs and it could be used as the most effective drug vehicle. The attachment of AL, ET drugs as well as the AL-CNT-3HPO and ET-CNT-3HPO drug-carrier systems to the bone tissue was modelled by optimization of the structures of these compounds bonded to the hydroxyapatite (HA)-17water (w). It was found that among these four systems, the AL-CNT-3HPO could be suggested as the most suitable DDS for application in the treatment of osteoporosis.