Simulation of the Adsorption and Release of Large Drugs by ZIF-8

Abstract

The adsorption and release of two drugs 5FU (5fluorouracil) and CAF (caffeine) into and from the ZIF-8 framework were simulated by the Gibbs-ensemble Monte Carlo approach employing two models for representing the sorbent: one without surface (ZIF-8P) and another with surface (ZIF-8S). The inner pores of ZIF-8S were inaccessible to the drugs, but accessible to the solvents (methanol or water). The ZIF-8P model is not recommended to describe the actual sorption processes because it lacks surface and solvent effects, which are reflected in the poor quantitative agreement with experimental results. The ZIF-8S model yielded results for the sorption of CAF in very close agreement with the experimental loading from methanol solution and release of the drug into water. For 5FU, the computer simulations provided qualitative agreements, which suggests that the sorbent−5FU interaction potentials should be improved. The excellent performance of the ZIF-8S model is due to its adequate description of the surface and by exposing adsorption sites such as undercoordinated zinc ions to interactions with large molecules. This was achieved by applying periodic conditions to a ZIF-8 nanocrystal, instead of an elementary cell, which is easy to generalize and used to describe several surface defects. Furthermore, the combination of this ZIF-8S model with the Monte Carlo method provides a very simple and efficient approach to simulate the inaccessibility of the ZIF-8 inner porosity to large molecules. Namely, any trial moves that inserted the drug within the pore were disregarded. This is a quite simple and general approach that can be promptly applied to a large number of MOF sorbents and of drugs that cannot access the inner pores.

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“…Zeolitic imidazolate framework-8 (ZIF-8) is a porous crystalline material formed by the coordination of zinc ions and 2-methylimidazole that has excellent biocompatibility. Therefore, ZIF-8 is considered to be an ideal carrier for controlling the transportation and release of medicine that has excellent potential in biomedicine applications [ 71 , 72 ].…”

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“…It presents itself as a lamellar structure maintained through compensation between π–π stacking interaction and hydrogen bonds, resulting in a one-dimensional polymeric chain of densely interconnected lamellae. This conformation gives the coordination framework a central octahedral pattern shared by tetragonal and hexagonal faces, with cavities of about 11.6 Å and 0.4 nm 3 that contribute to a wide surface area and that can be used for the delivery of drugs and the use of the ZIF-8 as a carrier 25 – 30 .…”

“…Because it is the second most abundant metal in the human body and the imidazole group is found in the amino acid histidine, ZIF-8 has good biocompatibility and safety 26 . Thus, ZIF-8 has potential as a pharmaceutical adjuvant due to its adsorption capacity followed by the release of drugs, whether hydrophilic or hydrophobic given its organic–inorganic composition 28 – 30 . In addition, as it has a flexible structure, the ZIF-8 presents a phenomenon called breathing, which ends up promoting a modulated release of drugs.…”

Modelling drug adsorption in metal–organic frameworks: the role of solvent

“…64 The host-adsorbate energy (U HA ) can be a major contributing factor in determining the adsorption of adsorbate drug and solvent molecules in MOFs. 29 The total potential energy of drugs in a MOF (i.e., total sum of host-adsorbate and adsorbateadsorbate energy) regulates the drug entrapment and release mechanism. 24 Therefore, by using the production run of the last 500 000 GCMC cycles, we calculated U HA for all the systems at all simulated pressures as presented in Fig.…”