Abstract
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.
Highlights
Metal-organic frameworks (MOFs) are a new class of highly tunable hybrid materials coordinated by metal and organic bridging ligand, have emerged as promising drug delivery system
The results revealed that Materials of Institute Lavoisier (MIL)-101-NH2 of average size-158 nm with high yield (70%) and high surface area (2347 m2/g) could be produced and reproducibly at a selected condition
The results conclude that processing parameters such as temperature pH and reactant concentration obtained from Central composite design (CCD)-response surface methodology (RSM) significantly affect the main constraints, i.e., surface area, particle size, and yield
Summary
Metal-organic frameworks (MOFs) are a new class of highly tunable hybrid materials coordinated by metal and organic bridging ligand, have emerged as promising drug delivery system. It was found that drugs with polar complexing groups bind eventually to the coordinative unsaturated iron Lewis acid sites (CUS), leading to high encapsulation efficiencies, high payloads, and controlled release [4,5]. Their tunable pore sizes, shapes large surface area to volume ratio (3100–5900 m2/g), intrinsic biodegradability [6], and tailored functionalities have provided a good choice in various applications such as gas storage, catalysis, and chemical sensing, molecular transport, adsorption of organic and inorganic molecules, and luminescence and electrode material [7]. These properties are beneficial in efficient drug delivery [8]
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