APPLICATION OF CENTRAL COMPOSITE DESIGN AND RESPONSE SURFACE METHODOLOGY FOR OPTIMIZATION OF METAL ORGANIC FRAMEWORK: NOVEL CARRIER FOR DRUG DELIVERY
Objective: The aim of the present study is to optimize the synthesis method of metal-organic framework (MOF) for high yield and larger surface area with minimum size for efficient drug loading.
Materials and Methods: Materials of Institute Lavoisier (MIL)-101-NH2 was synthesized by microwave-assisted hydrothermal method. Central composite design (CCD) under response surface methodology (RSM) was used for optimization. Process optimization was done by validating the model to obtain maximum surface area, maximum yield, and minimum particle size. Final obtained formulation was characterized by particle size and zeta potential, scanning electron microscopy, powder X-ray diffraction, Fourier-transform infrared spectroscopy, Brunauer–Emmett–Teller, and thermogravimetric analysis. Furthermore, gemcitabine (GEM) was used as a model drug for encapsulation in these MOFs for drug delivery carriers.
Results: The results revealed that MIL-101-NH2 of average size-158 nm with high yield (70%) and high surface area (2347 m2/g) could be produced easily and reproducibly at a selected condition. This enhances the drug delivery application of the valuable MIL-101-NH2. Optimized values for these parameters were 170°C, 5.00, and 1:1:400 for temperature, pH, and reactant ratio, respectively. MIL-101-NH2 appeared as a promising carrier for GEM delivery with higher encapsulation (77.7±2%) and loading (22.6±2%).
Conclusion: The results conclude that processing parameters such as temperature pH and reactant concentration obtained from CCD-RSM significantly affect the main constraints, i.e., surface area, particle size, and yield. The faster encapsulation of GEM in MOF makes them a promising carrier for drug delivery application.
2. Agostoni V, Chalati T, Horcajada P, Willaime H, Anand R, Semiramoth N, et al. Towards an improved anti-HIV activity of NRTI via metal-organic frameworks nanoparticles. Adv Healthc Mater 2013;2:1630-7.
3. Férey G, Mellot-Draznieks C, Serre C, Millange F, Dutour J, Surblé S, et al. A chromium terephthalate-based solid with unusually large pore volumes and surface area. Science 2005;309:2040-2.
4. Agostoni V, Horcajada P, Noiray M, Malanga M, Aykaç A, Jicsinszky L, et al. A “green” strategy to construct non-covalent, stable and bioactive coatings on porous MOF nanoparticles. Nature 2015;5:7925-32.
5. di Nunzio MR, Agostoni V, Cohen B, Gref R, Douhal A. A “ship in a bottle” strategy to load a hydrophilic anticancer drug in porous metal organic framework nanoparticles: Efficient encapsulation, matrix stabilization, and photodelivery. J Med Chem 2014;57:411-20.
6. Huxford RC, Rocca JD, Lin W. Metal-organic frameworks as potential drug carriers. Curr Opin Chem Biol 2010;14:262-8.
7. Horcajada P, Serre C, Vallet-Regí M, Sebban M, Taulelle F, Férey G, et al. Metal-organic frameworks as efficient materials for drug delivery. Angew Chem Int Ed Engl 2006;45:5974-8.
8. Saghanejhad TM, Zare-DR. Highly efficient simultaneous ultrasonic-assisted adsorption of methylene blue and rhodamine B onto metal organic framework MIL-68(Al): Central composite design optimization. RSC Adv 2016;6:27416-25.
9. Horcajada P, Chalati T, Serre C, Gillet B, Sebrie C, Baati T, et al. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. Nat Mater 2010;9:172-8.
10. Jhung SH, Lee JH, Yoon JW, Serre C, Férey G, Chang JS. Microwave synthesis of chromium terephthalate MIL-101 and its benzene sorption ability. Adv Mater 2017;19:121-4.
11. Curi? A, Reul R, Möschwitzer J, Fricker G. Formulation optimization of itraconazole loaded PEGylated liposomes for parenteral administration by using design of experiments. Int J Pharm 2013;448:189-97.
12. Amir AS, Praveen DC, Sagar SH. A design of experiment approach for optimization and characterization of etodolac ternary system using spray drying. Int J Pharm Pharm Sci 2017;9:223-40.
13. Shekar P, Kumar KS, Jabasingh SA, Radhakrishnan M, Balagurunathan R. Optimization of medium components for antibacterial metabolite production from marine streptomyces sp. Pua2 using response surface methodology. Int J Pharm Pharm Sci 2014;6:475-80.
14. Khan NA, Kang IJ, Seok HY, Jhung SH. Facile synthesis of nano-sized metal-organic frameworks, chromium-benzenedicarboxylate, MIL- 101. Chem Eng J 2011;166:1152-7.
15. Agostoni V, Anand R, Monti S, Hall S, Maurin G, Horcajada P, et al. Impact of phosphorylation on the encapsulation of nucleoside analogues within porous iron(iii) metal-organic framework MIL-100(Fe)
nanoparticles. J Mater Chem B 2013;1:4231-42.
16. Jyoti K, Pandey RS, Kush P, Kaushik D, Jain UK, Madan J, et al. Inhalable bioresponsive chitosan microspheres of doxorubicin and soluble curcumin augmented drug delivery in lung cancer cells. Int J Biol Macromol 2017;98:50-8.
17. Sumithra S, Shanmugasundaram P, Ravichandiran V. Quality by design-based optimization and validation of new reverse phase-high-performance liquid chromatography method for simultaneous estimation of levofloxacin hemihydrate and ambroxol hydrochloride in bulk and its pharmaceutical dosage form. Asian J Pharm Clin Res 2016;9:190-6.
18. Chalati T, Horcajada P, Couvreur P, Serre C, Ben Yahia M, Maurin G, et al. Porous metal organic framework nanoparticles to address the challenges related to busulfan encapsulation. Nanomedicine (Lond) 2011;6:1683-95.
19. Kumar S, Varma M, Prakash R. Development and optimization of enzalutamide-loaded solid lipid nanoparticles using box-behnken design. Asian J Pharm Clin Res 2019;12:67-76.
20. Di Renzo F. Zeolites as tailor-made catalysts: Control of the crystal size. Catal Today 1998;41:37-40.
21. Jhung SH, Lee JH, Chang JS. Crystal size control of transition metal ion-incorporated aluminophosphate molecular sieves: Effect of ramping rate in the syntheses. Microporous Mesoporous Mater 2008;112:178-86.
22. Seetharaj R, Vandana PV, Arya P, Mathew S. Dependence of solvents, pH, molar ratio and temperature in tuning metal organic framework architecture. Arabian J Chem 2019;12:295-315.
23. Baes CF, Mesmer RE. The Hydrolysis of Cations. New York: John Wiley and Sons; 1976.
24. Yu Q, Zhang X, Bian H, Liang H, Zhao B, Yan S, et al. ph-Dependent Cu(II) coordination polymers with tetrazole-1-acetic acid: Synthesis, crystal structures, EPR and magnetic properties. Cryst Growth Des 2008;8:1140-6.
25. Wyszogrodzka G, Doro?y?ski P, Gil B, Roth WJ, Strzempek M, Marsza?ek B, et al. Iron-based metal-organic frameworks as a theranostic carrier for local tuberculosis therapy. Pharm Res 2018;35:144.
26. Wu B, Lin X, Ge L, Wu L, Xu T. A novel route for preparing highly proton conductive membrane materials with metal-organic frameworks. Chem Commun (Camb) 2013;49:143-5.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.