(198ag) Study of ZIF-8 MOF?s as Viable Drug Carriers

Metal-organic frameworks (MOFs) are compounds consisting of metal ions or clusters coordinated to organic ligands forming one-, two-, or three-dimensional structures. MOFs are considered a subclass of polymer clusters with reticular structures. There are more than. 20,000 different reported MOFs within the last decade, and their properties vary because of the nature of the metal compounds (ions or clusters) and ligands⁴.

The most common used ligands or organic units are ditopic or polytopic organic carboxylates, imidazoles, or other molecules with active heteroatoms. When linked to metal-containing units, yield architecturally robust crystalline MOF structures with a typical porosity of greater than 50% of the MOF crystal volume. The surface area values of MOFs typically range from 1000 to 10,000 m2/g, thus exceeding those of traditional porous materials such as zeolites and carbons⁴. To date, MOFs are more extensive in their variety and multiplicity than any other class of porous materials. Generally these frameworks are used for absorption or adsorption of different gases, such as methane, CO₂ and hydrogen. Taking advantage of their large contact area and chemical tuning, MOFs are also used for catalysis and as sensors or indicators for gases and disperse components in solution⁴.

Recent studies are facing to use MOFs in medical applications such as drug transportation. Target molecules can be stored, transported and delivered in a specific and controlled manner at precise locations without modifying or disrupting the purpose or function of the bioactive molecules. Reports show the use of MOFs and other nano-materials for direct drug administration, stabilization of the drug through encapsulation or surface attachment, aid in cellular internalization, targeting delivery to a specific cell population, and providing controlled release of the drug at the designated target³. Organic-based drug delivery systems (DDSs) including lipid- and polymer-based systems which are already approved for clinical use¹. The use of inorganic nanomaterials such as MOFs in biological research represents one of the fastest growing areas of interest. Some examples of the effective use of the MOFs in DDSs with reported viability are ZIF-6 in anticancer drugs delivery and transport. Such as MOFs MIL-100 and MIL-101 achieving absorption of ibuprofen and the MOFs ZJU-101, MOF-74-FE(III) and Bio-MOF-1 tested to load diclofenac and deliver it to specific inflamed areas^2,3.

In this work zinc-2-methylimidazole framework (ZIF-8) is used as encapsulation system for different bioactive molecules. Stability of the clusters was analyzed in acid media⁶. ZIF-8 is a nontoxic molecule built from a salt of zinc and 2-methylimidazolate as organic ligand. This MOF has pores of 3.4 Å of diameter and a cavity of 11.6 Å of diameter. This material is stable under physiological conditions that gives it the potential of being an effective storage for bio-active molecules³.

The bio-active molecules were provided by the “Bioactive Molecule Synthesis Research Group” of the La Salle University Mexico. The molecules comprise a family of derivatives of Pyrazino[2,3-b]quinoline-10(5H)-one (PZQ) with different functional groups. Zinc nitrate hexa-hydrated and 2-methylimidazole were purchased from chemical distributors and used without further purification. Encapsulation is performed using one-pot synthesis⁴ by mixing a solution of the Bio-active molecule and 2-methylimidazole in methanol whit the solution of zinc nitrate hexahydrate in methanol at room temperature. The solution is mixed for 30 minutes and then centrifuged at 1500 RPM for 10 minutes to remove the supernatants. The material is washed with DI water in three consecutive cycles and dried in the oven at 50°C for 3 hours.

The efficiency of encapsulation has been determined by measuring the bioactive molecules in the supernatant of the reaction mixtures using UV-Vis spectrophotometry and FT-IR. Solid structures have been characterized by FT-IR and X-ray diffraction. No important difference in microstructure is observed between ZIF-8 alone and the MOF with the encapsulated bioactive molecule; which we assume there is no chemical interaction between cages and encapsulated molecules.

Stability of the cages has been analyzed in different pH systems observing the MOF disintegrates in strong base and acid media which implies that biomolecules can be delivered in the gastric system. Studies of biocompatibility and acute toxicity are being carried out to determine the viability of the use of these materials as drug delivery systems.

References:

[1] Emmanuel N. Koukaras, Tamsyn Montagnon,Pantelis Trikalitis, Dimitrios Bikiaris, Aristides D. Zdetsis, and George E. Froudakis. «Toward Efficient Drug Delivery through Suitably Prepared Metal−Organic Frameworks: A First-Principles Study.» The journal of Physical Chemistry, 2014: 8885-8990.

[2] Jia Zhuang, Chun-Hong Kuo, Lien-Yang Chou, De-Yu Liu, Eranthie Weerapana, and Chia-Kuang Tsung. «Optimized Metal-Organic-Framework Nanospheres for Drug Delivery: Evaluation of Small-Molecule Encapsulation.» ACSNANO, 2014: 2812-2819.

[3] Kyo Sung Park, Zheng Ni, Adrien P. Cöté, Jae Yong Choi, Rudan Huang, Fernando J. Uribe-Romo, Hee K. Chae,. «Exceptional chemical and thermal stability of zeolitic imidazolate frameworks.» PNAS, 2006: 10186-10191.

[4] Paolo Falcaro, Raffaele Ricco, Cara M. Doherty, Kang Liang, Anita J. Hillb and. «MOF positioning technology and device fabrication.» Royal Society of Chemistry, 2014: 49.

[5] Patricia Horcajada, Christian Serre, Guillaume Maurin, Naseem A. Ramsahye,Francisco Balas, Marı´a Vallet-Regí, Muriel Sebban, Francis Taulelle, and Gérard Férey. «Flexible Porous Metal-Organic Frameworks for a Controlled Drug Delivery.» JACS articleas, 2008: 6774-6780.

[6] Yanyu Yang, Quan Hu, Qi Zhang, Ke Jiang, Wenxin Lin, Yu Yang, Yuanjing Cui, and Guodong Qian. «A Large Capacity Cationic Metal-Organic Framework Nanocarrier for Physiological pH Responsive Drug Delivery.» American Chemical Society, 2016: 17.