Molecular mechanism of drug transport and release through zeolitic imidazole framework nanospheres for versatile drug delivery applications

Adsorption and release of doxorubicin (DOX) anticancer drug on two bio-compatible zeolitic imidazolate frameworks (ZIFs), namely ZIF7 and ZIF8, are studied using molecular dynamics (MD) simulation. Furthermore, the diffusion of the studied system into the cell membrane (POPC) is investigated. The obtained results reveal that ZIF7 is favorable for DOX adsorption compared to ZIF8 due to the formation of strong binding with DOX. Furthermore, the low diffusion coefficient value for drug molecules in both ZIFs suggests that they can be interesting candidates for controlled release of the doxorubicin anticancer drug. Moreover, the study of drug release in acidic pH shows that the electrostatic energy in the protonated system is weaker than those in the neutral systems. Our results indicate that DOX remains bound to the ZIFs in its neutral state, yet it is readily released in acidic conditions. Finally, the behavior of the DOX-ZIF7 system near the membrane cell is studied. It is found that the DOX tends to stay near the head of the lipids and cannot be inserted into the POPC bilayer during simulation time while ZIF7 moves away from the lipid membrane. The obtained results from the MD simulation reveal that ZIF7 can deliver the drug to the top of the lipid bilayer.