Kajian Metal–Organic Frameworks (MOFS) sebagai Material Baru Pengantar Obat

Qonita Awliya Hanif, Reva Edra Nugraha, Witri Wahyu Lestari

Abstract

Metal–Organic Frameworks (MOFs) merupakan material berpori baru yang berpotensi sebagai pengantar dan pelepas lambat obat. Strukturnya yang fleksibel, ukuran pori kristalin yang teratur, dan sisi koordinasi yang beragam merupakan beberapa kelebihan dari MOFs yang mendukung dalam enkapsulasi berbagai obat. Metode yang dapat digunakan untuk sintesis MOFs diantaranya nanopresipitasi, solvothermal, reverse microemulsion, dan reaksi solvothermal dengan template surfaktan. Karakterisasi material hasil sintesis maupun profil setelah enkapsulasi (loading) dapat dilakukan menggunakan Scanning Electron Micrscope (SEM), Transmission Electron Microscope (TEM), Differential Scanning Calorymetry (DSC), Fourier Transform Infra Red Spectroscopy (FTIR), dan Powder X-Ray Diffraction (PXRD). Metode loading obat terdiri dari dua kategori, yakni penggabungan agen biomedis secara langsung dan loading secara post synthesis. Sebelum MOFs diaplikasikan, perlu dilakukan aktivasi dan penempelan material obat. Pengujian lepas lambat dapat dijalankan pada beberapa kondisi seperti dalam Simulated Body Fluid (SBF), Phosphate Buffer Saline (PBS), Bovine Serum Albumin (BSA) maupun simulasi menggunakan Grand Canonical Monte Carlo (GCMC). Pengujian secara in vivo dan in vitro juga dapat dilakukan untuk mengetahui dampaknya pada tubuh makhluk hidup dan aktivitasnya terhadap sel patogen. Kombinasi organik linker dan ion logam pusat yang berbeda akan menghasilkan ukuran pori, fleksibilitas, kapasitas loading, profil pelepasan obat, toksisitas, dan kemampuan menginhibisi yang berbeda pula. Pada review kali ini akan dibahas tentang kajian singkat terkait struktur dan desain MOFs, bio-MOFs, nano bio MOFs, strategi sintesis, dan strategi loading dan pelepasan obat untuk aplikasi dalam biomedis. Selanjutnya akan diberikan beberapa contoh aplikasi yang sudah dilakukan sejauh ini misalnya beberapa jenis MOFs yang sudah dienkapsulasi dengan beberapa material obat, seperti 5-fluoracil, ibuprofen, doxorubicin, dan dikaji waktu pelepasannya dan interaksinya dengan permodelan komputasi.

Study of Metal–Organic Frameworks (MOFs) as a Novel Material for Drug Delivery. Metal–Organic Frameworks (MOFs) are a novel class of porous material that has wide potential applications including in drug delivery and slow release. Its flexible structure, regular crystalline pore size, and various coordination sites are some of the advantages of supporting MOFs properties in the encapsulation of various drugs. Various methods can be used for the MOFs synthesis include nanoprecipitation, solvothermal, reverse micro emulsion, and surfactant-templated solvothermal. Both characterization for synthesized materials and profile after encapsulation can be done using Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infra-Red Spectroscopy (FTIR), and Powder X-Ray Diffraction (PXRD). The drug loading method consists of two categories, namely the direct incorporation of biomedical agents and post-synthesis method. Before MOFs are applied in biomedical application, activation and attachment of medicinal materials should be performed. Meanwhile, for slow release testing can be run on several conditions such as in Simulated Body Fluid (SBF), Phosphate Buffer Saline (PBS), Bovine Serum Albumin (BSA) and simulation using Grand Canonical Monte Carlo (GCMC). In vivo and in vitro testing can also be done to determine the impact on the body of living creatures and their activity on pathogen cells. Different organic linker and metal center combinations will result in pore size, flexibility, loading capacity, drug release profiles, toxicity, and different inhibiting ability. Herein, we will discuss a brief review of the structure and design of MOFs, bio-MOFs, nano-bio MOFs, synthesis, drug loading and release strategies for applications in biomedicine. Furthermore, there will be some examples of applications that have been done so far, e.g. some types of MOFs that have been encapsulated with some medicinal materials, such as 5-fluorouracil, ibuprofen, doxorubicin, and reviewed its release time and interaction with computational modeling.

Keywords

biomedis; enkapsulasi; MOFs; obat; pelepas lambat

Full Text:

PDF

References

Abid, H. R., Tian, H., Ang, H. M., Tade, M. O., Buckley, C. E. and Wang, S., 2012. Nanosize Zr-Metal Organic Frameworks (UiO-66) for Hydrogen and Carbon Dioxide storage. Chemical Engineering Journal 187, 415-420.

Allendorf, M. D., Bauer, C. A., Bhakta, R. K. and Houk, R. J. T., 2009. Critical Review: Luminescent Metal Organic Frameworks. Chemical Society Reviews 38, 1330–1352.

Bangham, A. D. and Horne, R. W., 1964. Negative Staining of Phospholipids and Their Structural Modification by Surface-active Agents as Observed in the Electron Microscope. Journal of Molecular Biology 8, 660–668.

Bernini, M. C., Jimenez, D. F., Pasinetti, M., Pastor, A. J. R. dan Snurr, R. Q., 2014. Screening of Bio-Compatible Metal–Organic Frameworks as Potential Drug Carriers using Monte Carlo Simulations. Journal of Materials Chemistry B 2, 766-774

Cho, H. Y., Yang, D. A., Kim, J., Jeong, S. Y., and Ahn, W. S., 2012. CO2 Adsorption and Catalytic Application of Co-MOF-74 Synthesized by Microwave Heating. Catalysis Today 185, 35-40.

Eddaoudi, M., Kim, J. Rosi, N., Vodak, D., Wachter, J., O’Keeffe, M., and Yaghi, O. M. 2002. Systematic Design of Pore Size and Functionality in Isoreticular MOFs and Their Application in Methane Storage. Science 295, 469–472.

Fromm, K. M., 2008. Coordination Polymer Network with S-Block Metal Ions. Coordination Chemistry Reviews 252, 856-885.

Gordon, J., Kazemian, H., and Rohani, S., 2015. MIL-53(Fe), MIL-101, and SBA-15 Porous Materials: Potential Platforms for Drug Delivery. Materials Science and Engineering C 47, 172–179.

Goyer, R. A., 1996. Toxic Effects of Metals, In Casarett & Doull’s Toxicology, The Basic Science of Poisons. Klaassen, C. D., McGraw Hill Health Professions Division, ISBN 0071054766.

Hashemipour, S. and Panahi, H. A., 2017. Fabrication of Magnetite Nanoparticles Modified with Copper Based Metal Organic Framework for Drug Delivery System of Letrozole. Journal of Molecular Liquids, doi: 10.1016/j.molliq.2017.07.127.

He, Q. and Shi. J., 2011. Mesoporous Silica Nanoparticle based Nano Drug Delivery Systems: Synthesis, Controlled Drug Release and Delivery, Pharmacokinetics and Biocompatibility. Journal of Materials Chemistry 21, 5845-5855.

Hinks, N. J., McKinlay, A. C., Xiao, B., Wheatley, P. S., and Morris, R. E., 2010. Metal Organic Frameworks as NO Delivery Materials for Biological Applications. Microporous and Mesoporous Materials 129, 330 – 334.

Horcajada, P., Alvarez, C. M., Ramila, A., Pariente, J. P., and Regí, M. V., 2006. Controlled Release of Ibuprofen from Dealuminated Faujasites. Solid State Science 8 (12), 1459-1465.

Horcajada, P., Chalati, T., Serre, C., Gillet, B., Sebrie, C., Baati, T., Eubank, J. F., Heurtaux, D., Clayette P., Kreuz, C., Chang, J., Hwang, Y. K., Marsaud, V., Bories, P. N., and Cynober, L., 2010. Porous Metal-Organic Frameworks Nanoscale Carriers as Potential Platform for Drug Delivery and Imaging. Nat. Mat 9, 172-178.

Horcajada, P., Serre, C., Regí, M. V., Sebban, M., Taulelle, F. and Férey, G., 2006. Metal Organic Frameworks as Efficient Materials for Drug Delivery. Angewandte Chemie International Edition 45 (36), 5974-5978.

Horcajada, P., Serre, C., Regí, M. V., Sebban, M., Taulelle, F., and Férey, G., 2008. Porous Metal-Organic Frameworks for a Controlled Drug Delivery. Journal of the American Chemical Society 130, 6774–6780.

Joaristi, A. M., Juan-AlcanÞiz, J., Serra-Crespo, P., Kapteijn, F., and Gascon. J., 2012. Electrochemical Synthesis of some Archetypical Zn2+, Cu2+ and Al3+ Metal Organic Frameworks. Crystal Growth 12, 3489-3498.

Kathryn, M., Taylor, L., Jin, A., and Lin, W., 2008. Angewandte Chemie International Edition 47, 7722 –7725.

Ke, F., Yuan, Y. P., Qiu, L. G., Shen, Y. H., Xie, A. J., Zhu, J. F., Tianc, X. Y., and Zhang, L. D., 2011. Facile Fabrication of Magetic Metal-Organic Frameworks Nanocomposites for Potential Targeted Drug Delivery. Journal of Materials Chemistry 21, 3843-3848.

Keskin, S. and Kızılel, S., 2010. Review: Biomedical Applications of Metal Organic Frameworks. Industrial Engineering Chemistry Research 50, 1799-1812.

Kroncke, K. D. and Suschek, C.V., 2008. Addulterated Effects of Nitric Oxide-Generating Donors. Journal of Investigative Dermatology 128, 258-260.

Lee, J. Y., Farha, O. K., Roberts, J., Scheidt, K. A., Nguyen, S. T, and Hupp, J. T., 2009. Review: Metal Organic Frameworks as Catalysts. Chemical Society Reviews 38, 1450–1459.

Lestari, W. W., Arvinawati, M., Martien, and R., Kusumaningsih, T., 2018. Green and Facile Synthesis of MOF and Nano MOF Containing Zinc(II) and Benzen 1,3,5-Tri Carboxylate and Its Study in Ibuprofen Slow-Release. Materials Chemistry and Physics 204, 141-146.

Li, H., Eddaoudi, M., O’Keeffe, M. and Yaghi, O. M., 1999. Design and Synthesis of an Exceptionally Stable and Highly Porous Metal Organic Frameworks. Nature 402, 276-279.

Li, J-R., Kuppler, R. J. and Zhou, H. C., 2009. Review: Selective Gas Adsorption and Separation in Metal Organic Frameworks. Chemical Society Reviews 38, 1477–1504.

Li, L., Liu, Y., Sun, K., He, Y., Liu, L., 2017. One Step Synthesis of Magnetic Composite Fe3O4/Cu-BTC/GO. Materials Letters 197, 196–200

Li, L., Wu, Y. Q., Sun, K. K., Zhang, R., Fan, L., Liang, K. K., and Mao, L. B., 2016. Controllable Preparation and Drug Loading Properties of Core-Shell Microspheres Fe3O4@MOFs/GO. Materials Letters 162, 207-210

Liu, B., He, Y., Han, L., Singh, V., Xu, X., Guo, T., Meng, F., Xu, X., York,

P., Liu, Z., and Zhang, J., 2017. Microwave-Assisted Rapid Synthesis of γ-Cyclodextrin Metal–Organic Frameworks for Size Control and Efficient Drug Loading. Crystal Growth Design 17, 1654–1660

Lucena, F. R. Q. S, Larissa, C. C., Rodrigues, M. D., Silva, T. G., Pereira, V. R. A., Milita˜o, G. C. G., Fontes D. A. F., Pedro, J. R. N., Silva, F. F., and Nascimento, S. C., 2013. Induction of Cancer Cell Death by Apoptosis and Slow Release of 5-fluoracil from Metal-Organic Frameworks Cu-BTC. Biomedicine & Pharmacotherapy 67, 707–713.

Ma, L. Q., Falkowski, J. M., Abney, C., and Lin, W. B., 2010. A Series of Isoreticular Chiral Metal-Organic Frameworks as a Tunable Platform for Asymmetric Catalysis. Nat. Chem. 2, 838–846.

Ma, L., Jin, A., Xie, Z., and Lin, W., 2009. Freeze Drying Significantly Increases Permanent Porosity and Hydrogen Uptake in 4,4-Connected Metal Organic Frameworks. Angewandte Chemie International Edition 48, 9905–9908.

McKinlay, A.C., B. Xiao, D.S. Wragg, P.S. Wheatley, I.L. Megson, dan R.E. Morris, 2008. Exceptional Behavior Over the Whole Absorption-Storage-Delivery Cycle for NO in Porous Metal Organic Frameworks. Journal of the American Chemical Society, 130, 10440-10444.

Miller, S. R., Heurtaux, D., Baati, T., Horcajada, P., Grene`che, J. M., and Serre., 2010. Biodegradable Therapeutic MOFs for the Delivery of Bioactive Molecules. C. Chemical Communication 46, 4526-4528.

Mueller, U., Schubert, M., Teich, F., Puetter, H. Schierledantt, K., and Pastre, J., 2006. Application: Metal Organic Frameworks Prospective Industrial Applications. Journal of Materials Chemistry 16, 626-636.

Parzuchowski, P. G., Frost, M. C., and Meyerhoff, M. E., 2002. Synthesis and Characterization of Polymethacrylate based Nitric Oxide Donors. Journal of the American Chemical Society 124 (41), 12182-12191.

Qiu, L. G., Li, Z. Q., Wu, Y., Wang, W., Xu, T., and Xia Jiang 2008, Facile Synthesis of Nanocrystals of a Microporous Metal–Organic Framework by an Ultrasonic Method and Selective Sensing of Organoamines. Chemical Communications, 3642–3644

Riehemann, K., Schneider, S. W., Luger, T. A., Godin, B., Ferrari, M., and Fuchs, H. 2009. Review: Nanomedicine-Challenge and Perspective. Angewandte Chemie International Edition 48, 872–897.

Rieter, W. J., Pott, K. M., Taylor, K. M. L., and Lin, W., 2008. Nanoscale Coordination Polymers for Platinum-Based Anticancer Drug Delivery. Journal of the American Chemical Society 130, 11584–11585.

Rieter, W. J., Taylor, K. M. L., An, H., Lin, W., and Lin, W., 2006. Nanoscale Metal-Organic Frameworks as Potential Multimodal Contrast Enhancing Agents. Journal of the American Chemical Society 128, 9024–9025.

Rocca, J. D., Liu, D., and Lin, W., 2011. NMOFs for Biomedical Imaging dan Drug Delivery. Accounts of Chemical Research 44 (10), 957–968.

Rosi, N. L., Eckert, J., and Eddaodi, M., 2003. Hydrogen Storage in Microporous Metal Organic Frameworks. Science 300 , 1127–1129.

Seo, Y. K., Hundal, G., Jang, I. T., Hwang, Y. K., Jun, C. H. and Chang, J. S., 2009. Microwave Synthesis of Hybrid Anorganic-Organic Materials Including Porous Cu3(BTC)2 from Cu(III)-Trimesat Mixture. Microporous Mesoporous Materials 119 (1), 331-337.

Shi, J., Votruba, A. R., Farokhzad, O. C., and Langer, R., 2010. Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications. Nano Letter 10, 3223–3230.

Shin, J. H. and Schoenfisch, M. H., 2008. Inorganic/Organic Hybrid Silica Nanoparticles as a Nitric Oxide Delivery Scaffold. Chemistry of Materials 20, 239-249.

Sindoro, M., Yanai, N., Jee, A., dan Granick, S., 2014. Colloidal-Sized Metal-Organic Frameworks: Synthesis and Application. Accounts of Chemical Research 47 (2), 459–469.

Singco, B., Liu, L.H., Chen, Y. T., Shih, Y. H., Huang, H. Y., Lin, C. H., 2015. Approaches to Drug Delivery: Confinement of Aspirin In MIL-100(Fe) and Aspirin in The De Novo Synthesis of Metal-Organic Frameworks. Microporous and Mesoporous Materials, doi: 10.1016/j.micromeso.2015.08.017.

Sun, C. Y., Qin, C., Wang, X. L., and Su, Z. M., 2013. Review: Metal Organic Frameworks as Potential Drug Delivery Systems. Expert Opinion on Drug Delivery 10 (1), 89-101.

Sun, K., Li, L., Yu, X. L., Liu, L., Meng, Q., Wang, F., and Zhang, R., 2017. Functionalization of mixed ligand metal organic frameworks as the transport vehicles for drugs. Journal of Colloid and Interface Science 486, 128–135

Taylor, K. M. L., Della, R. J., Xie, Z., Tran, S., and Lin, W., 2009. Postsynthetic Modifications of Iron-Carboxylate Nanoscale Metal Organic Frameworks for Imaging and Drug Delivery. Journal of the American Chemical Society 131, 14261 –14263.

Taylor, K. M. L., Rieter, W. J., and Lin, W., 2008. Manganese-based Nanoscale Metal-Organic Frameworks for Magnetic Resonance Imaging. Journal of the American Chemical Society 130, 14358–14359.

Taylor, K. M. L., Rocca, J. D., Huxford, R. C., Lin, W., 2010. Feature Article: Hybrid Nanomaterials for Biomedical Applications. Chemical Communication 46, 5832-5849.

Tranchemontagne, D. J., Cortes, J. L. M., O'Keeffe, M., and Yaghi, O. M., 2009. Review: Secondary Building Units, Nets and Bonding in the Chemistry of Metal-Organic Frameworks. Chemical Society Reviews 38 1257–1283.

Vasconcelos, I.B., Wanderley, K.A., Rodrigues, N.M., da Costa Jr., N.B., Freire, R.O., Junior, S.A., 2016. Host-guest interaction of ZnBDC-MOF + doxorubicin: A theoretical and experimental study. Journal of Molecular Structure, doi: 10.1016/j.molstruc.2016.11.034

Vimont, A., Goupil, J. M., Lavelley, J. C., Daturi, M., Surble, S., Serre, C., Millange, F., Ferrey, G., and Audebrand, N., 2006. Investigation of Acid Sites in Zeotypic Giant Pores Chromium(III) Carboxylate. Journal of the American Chemical Society 128, 3218–3227.

Wagner, V., Dullaart, A., Bock, A. K., and Zweck, A., 2006. The Emerging Nanomedicine Landscape. Nature Biotechnology 24 (10), 1211–1217.

Wheatley, P. S., Butler, A. R., Crane, M. S., Fox, S., Xiao, B., Rossi, A. G., Megson, I. L., and Morris, R. E., 2006. NO-Releasing Zeolite and their Antithrombotic Properties. Journal of the American Chemical Society 128 (2), 502-509.

Xie, Z. Y., Huang, X., Wang, Z., Niu, L., Teng, M., and Li, J., 2007. Rational Design of MOFs Constructed from Modified Aromatic Amino Acids. Chemistry A European Journal 13, 9399 – 9405.

Yang, D. A., Cho, H. Y., Kim, J., Yang, S. T. and Ahn, W. S., 2012. CO2 Capture and Conversion Using Mg-MOF-74 Prepared by a Sonochemical Method. Energy Environmental Science 5, 6465-6473.

Zhang, J., Kuo, C. H., Chou, L. Y., Liu, D. Y., Weerapana, E., and Tsung, C. K., 2014. Optimized Metal-Organic Framework Nanospheres for Drug Delivery: Evaluation of Small-Molecule Encapsulation. American Chemical Society 8, (3), 2812–2819.

Zhu, H. F., Ka, B., and Murad. F., 2007. Nitric Oxide Accelerates the Recovery from Burns Wounds. World Journal of Surgery 31 (4), 624-631.

Refbacks

  • There are currently no refbacks.