Drug-Facilitated Crystallization of Spray-Dried CD-MOFs with Tunable Morphology, Porosity, And Dissolution Profile

Abstract

Metal–organic frameworks (MOFs) with versatile functionalities have applications in environmental science, sensor separation, catalysis, and drug delivery. In particular, MOFs used in drug delivery should be biodegradable and easy to control. In this study, spray-dried cyclodextrin-based MOFs (CD-MOFs) with tunable crystallinity, porosity, and dissolution properties were fabricated. The spray-drying precursor properties, such as ethanol volume ratio, incubation time, and precursor concentration, were optimized for controlled crystallization. On the basis of the morphology, X-ray diffraction peak intensity, and specific surface areas of the spray-dried CD-MOF products, they were categorized as amorphous, partially crystalline, and highly crystalline. An active pharmaceutical ingredient ketoconazole (KCZ) was introduced into the precursor to prepare KCZ-containing CD-MOFs. The surface areas of these products were greater by 3-fold (292 m2/g) than that of the plain CD-MOF (94.1 m2/g) prepared using the same parameters. The presence of KCZ in the hydrophobic cavity between the two γ-CD molecules was correlated to the CD-MOF crystal growth. Additionally, CD-MOF particles exhibited different dissolution behaviors on the basis of the position of KCZ in the MOF. These spray-dried CD-MOFs with tunable morphology, specific surface area, and dissolution could have potential applications in various fields.

Synergistic applications of cyclodextrin-based systems and metal–organic frameworks in transdermal drug delivery for skin cancer therapy

“…The articles catalogued in Table 3 primarily center on MOF-based transdermal systems as a potential remedy for melanoma and an array of wounds such as diabetic, chronic, and infected wounds. CD-MOFs have shown to be able to encapsulate various drugs and active compounds, including doxorubicin, 176,177 resveratrol, 140,178 epigallocatechin gallate, 179 vitamin A palmitate, 180 ascorbic acid derivatives, 181 myricetin, 182 ketoconazole, 183 salicylic acid, 140 ferulic acid, 140,163 different NSAIDs, 184 emodin and quercetin. 128…”

The antibacterial activity of three zeolitic-imidazolate frameworks and zinc oxide nanoparticles derived from them

“…Manipulating these parameters during their synthesis can result in MOFs with completely different characteristics. This has led many researchers to study MOFs due to their wide range of potential applications, such as catalysts, 11 electrochemical and chemical sensors, 12 encapsulating large molecules, 13 enzymes, 14,15 storing gas, 16,17 removal of hazardous heavy metals, 18 organic dyes and toxins, [19][20][21] water splitting, 22 exhibiting anti-bacterial and anti-cancer activities, [23][24][25][26] facilitating drug delivery [27][28][29][30] and etc. MOFs can be used as a source for releasing metal ions under controlled conditions.…”

“Wash-free” synthesis of cyclodextrin metal–organic frameworks

“…The cost of MOFs depends on the raw material costs (ligands, metal sources and solvents) and the manufacturing process (product recovery by filtration and other means, washing, drying, forming and processing), including capital investment, process energy, utilities and labor costs. 9,10 To address process simplification and cost reduction, various synthesis methods have been demonstrated, including solvothermal, hydrothermal, microwave-assisted, 11,12 sonochemical, 13,14 microfluidic, 15,16 aqueous solution, 17,18 spray-drying 19–22 and mechanochemical methods. 23–27 To date, the most conventional and common method for obtaining CD-MOF crystals is the vapor diffusion method.…”

“…It has already been reported that even if the structure of CD-MOF is amorphous, it has potential applications as a drug carrier. 21,22 The lack of potassium (especially under conditions of K + /CD < 1) causes defects in the CD bonds, resulting in reduced crystallinity, as shown in Scheme 1.…”

“…One of the reasons for this difference is that CD-MOF prepared by wash-free mechanochemical synthesis has a much larger BET area than that prepared by the spray-drying method (∼94.1 m 2 g −1 ). 21,22…”