Computational studies on the b12n12 as potential carriers in drug delivery systems for isoniazid drug

Mozhgan Sabzehzari,1,* Sepideh ahmadi-tabar,2



Recently, some efforts have been performed to find an appropriate carrier to deliver the drug, but it still needs much further studies. nanostructures have found numerous applications researches on the development of a drug carrier based on the nanostructures has been rapidly grown. boron nitride (bn) heterofullerenes have been already known as nanostructures with special physical and electronic properties. furthermore, bn heterofullerenes can be functionalized with various biological molecules. in 2009, chen et al. showed that bn nanostructures are noncytotoxic and can be functionalized for biological applications, and they used bn nanotubes as a carrier to deliver dna oligomers to the cells. these researches tempted us to investigate the ability of b12n12 fullerene as a carrier for isoniazid drug. isoniazid (iso) is always recommended as first-line anti-tuberculosis drugs, which has high effectivity and strong antibacterial action. however, drug resistance is a common problem during long-term therapy, which causes treatment failure leading to progressive disease. delivery of isoniazid drug directly to the target site using specific nanocarriers may be a potential strategy to reduce its side effects as well as toxicity. therefore, it is necessary to investigate the delivery of isoniazid drug using b12n12 in order to perform further pharmacological studies.


Our calculations are based on the ab initio density functional theory (dft) within three parameter m06/6-31+g** functional. the natural bond orbital (nbo) calculations and all calculations of homo-lumo gaps were also performed at the same level of theory. gaussian09 package was used for all calculations.


Results show that mainly the boron atom in b12n12 tends to have an interaction with the oxygen atoms of isoniazid. their structures have been optimized. we also calculated the change of enthalpy, gibbs free energy and entropy for the adsorption processes at 298 k and 1 atm. for our complexes, the calculated Δg values are less negative compared to the ead, indicating that upon the adsorption process the entropy is decreased because of a reduction of disorder of the system. the calculated negative values of Δs for complexes confirm this matter. the electric dipole moment of b12n12 is calculated to be zero but this value is non-zero for complexes which make them more soluble in polar solvents. the stretching vibrational mode of c-o bonds in the iso molecule is decreased in the complexes indicating that this bond is somewhat weakens upon the adsorption process because of a charge transfer. the values of homo, lumo and eg are also determined. the eg is a useful factor for determining the kinetic reactivity of materials and also its change upon the adsorption process indicates the sensitivity of an adsorbent to an adsorbate. the change of eg of adsorbent can help one to recognize the presence and attachment of the drug to the carrier. in one of the complexes, the interaction of bn nanocluster with the drug reduces intensively its eg which can help to detect the drug. in this structure, boron atom forms a chemical bond with o1 atom, and its adjacent nitrogen atom forms a hydrogen bond with the hydrogen atom of iso. therefore, there is a relatively strong interaction between iso and b12n12 molecules. the mep plot indicates that the electrostatic potential of n and b atom is largely negative and positive which makes the b sites proper for nucleophilic attack. after interaction with iso, the lumo of fullerene is shifted on the drug molecule in all complexes. the dos plot for b12n12 before and after interaction with iso shows that the lumo level sharply shifts which reduces the eg of the stablest complex. for the others, this decrease is larger and we predict a smaller eg. while there is no significant changes in homo level for b12n12 after the interaction with the iso molecule. moreover, the nbo analysis determines that the charge transfers from the iso to the b12n12 cage for all of complexes which are significant.


in the present research, dft calculations were performed to investigate the potential application of b12n12 as a carrier for drug delivery of isoniazid. our results indicated that the adsorption energy values of isoniazid on b12n12 were negative. moreover, the calculations showed that isoniazid was adsorbed on b12n12 in a thermodynamically favorable manner. the results of nbo analysis also revealed that the charge transfers from the iso to the b12n12 cage which are significant. finally, it was concluded that the b12n12 is potential carrier candidates to deliver the isoniazid drug into the target site.


Drug delivery, isoniazid drug, b12n12 fullerene, dft