Search Results (14)

Metal–organic frameworks (MOFs) are a versatile class of hybrid crystalline materials that have emerged as promising candidates for a broad range of applications. γ-cyclodextrin MOFs (γ-CD-MOFs) represent an innovative subgroup of MOFs constructed from “edible” γ-CD ligands coordinated with biocompatible metal ions to form an extended porous structure. Owing to their unique characteristics such as their “green” origin, biodegradability, and biocompatibility they became a promising platform for drug delivery applications. Structurally, γ-CD-MOF possess a body-centered cubic structure with dual-mode porosity, enabling the simultaneous encapsulation of hydrophilic and hydrophobic drugs. Such structural features contribute to high loading capacity, tunable release behavior, and enhanced stability of incorporated drugs. In this review, we comprehensively discuss the structural features of γ-CD-MOF, synthesis strategies, crystals size and morphology control, activation and drying techniques, and drug encapsulation approaches. We further address computational and simulation approaches used to predict and optimize drug-framework interactions, as well as post- synthetic modifications aimed at enhancing stability and functionality. The diverse pharmaceutical applications of γ-CD-MOFs are examined, including the delivery of small molecules, macromolecules, multi-drug systems, and emerging pulmonary formulations. Additionally, we examine biocompatibility and safety considerations and current limitations related to aqueous stability, industrial-scale production, and reproducibility. Finally, this review highlights recent progress and underlines future perspectives, emphasizing innovations such as fast drug-loaded MOF formation via spray-drying, co-delivery strategies, and vaccine-oriented formulations. Together, these insights highlight the potential of γ-CD-MOFs to shape the next generation of multifunctional drug delivery systems across interdisciplinary fields. Full article

Background/Objectives: γ-Cyclodextrin metal–organic frameworks (γ-CD-MOFs) are biocompatible porous crystalline materials that combine the advantages of both γ-cyclodextrins (γ-CDs) and MOFs, making them promising carriers for drug delivery. However, drug loading efficiencies into γ-CD-MOFs achieved by impregnation method involves complex interactions that necessitate further systematic exploration. This study aimed to determine the impregnation conditions that significantly impact tenoxicam (TNX) loading into γ-CD-MOFs and its aqueous solubility, and to identify the optimal possible conditions for maximizing both. Methods: A three-factor, three-level (3³) Box–Behnken factorial design technique was utilized. Results: Statistical analysis showed that TNX/γ-CD-MOF molar ratio exerted a significant positive effect on drug loading, whereas loading temperature and time have an insignificant effect. Additionally, while loading TNX into γ-CD-MOFs increased its water solubility, variations in the loading parameters did not produce a significant effect on this solubility. The impregnation conditions obtained from the numerical optimization step were a drug/MOF molar ratio of 1.99:1 at 29 ± 0.5 °C for 6 h, which experimentally showed TNX loading of 12.2 ± 1.55%. A discrepancy between the predicted and experimental drug-loading results was observed suggesting that the fitted model does not fully capture the complexity of the system, highlighting the need for experimental verification. Conclusions: This work delivers new insights into the impregnation factors governing TNX loading into γ-CD-MOFs and establishes a foundational framework for the future optimization of CD-MOFs-based drug formulations. Full article

Linalyl acetate (LA), a key volatile component in essential oils, is extensively utilized in fragrance, food, and cosmetic industries. Nevertheless, its practical applications are constrained by rapid evaporation and physicochemical instability. This study developed novel cyclodextrin–metal–organic frameworks (CD-MOFs) crystallized from β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) with potassium hydroxide, demonstrating superior structural properties for LA encapsulation. Through comparative analysis with native CDs, the synthesized CD-MOFs exhibited highly ordered crystalline architectures and uniform morphological characteristics. The LA encapsulation capacity of the γ-CD-MOF was systematically evaluated under different conditions using a three-level factorial design via RSM. Optimization revealed maximum encapsulation efficiency (25.9%) under ideal conditions—an LA:γ-CD-MOF mass ratio of 3.8:1, 60.9 °C incubation temperature, and 49.3 min processing time—representing a 2.39-fold enhancement over conventional CD encapsulation. Thermal stability analysis demonstrated remarkable improvement, with LA-γ-CD-MOF complexes showing an onset decomposition temperature of 215 °C, 135 °C higher than that of free LA. Compared with LA-γ-CD, LA coated with γ-CD-MOFs still retained 55.7% at 80 °C for 75 min, with the release rate reduced by about 45.3%. These findings establish the potential of γ-CD-MOFs as effective carriers for thermolabile and volatile compounds in functional food and cosmetic industries. Full article

Background/Objectives: Mometasone furoate (MF) is a topical corticosteroid used to reduce allergic and inflammation symptoms. In this study, MF was incorporated into the hydrophobic cavities of γ-cyclodextrin metal-organic frameworks (CD-MOFs) to prepare MF@MOF powders for nasal delivery. Methods: MF@MOF particles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and thermogravimetry. A transparent biomimetic model of the human nasal cavity was produced by 3D printing and used to evaluate intra-nasal depositions patterns. Results: Drug loading was optimized by incubating MF with a CD-MOF at a ratio of 4% for 1 h at 40 °C, and the cubic morphology and particle size of the nanoparticles were not altered using an incubation method. PXRD and FTIR analyses confirmed the successful loading of MF into the CD-MOF. Using a 3D biomimetic nasal cavity model, a 30° administration angle was found to result in reduced drug accumulation in the nasal vestibule and enhanced deposition in the respiratory and olfactory regions, compared with administration at 45°. Approximately 51% of the drug reached the respiratory zone in the model of the nasal cavity from male subjects, while almost 60% of the drug reached this zone in the model associated with female subjects. Compared with nasal sprays, nasal powder sprays had less deposition in the nasal vestibule and more deposits in the middle and inferior nasal concha. Conclusions: MF@MOF is suitable for intranasal administration. Delivery of MF as a nasal powder shows potential in the treatment of chronic rhinosinusitis. Full article

Objective: Muscone (MUS), a primary active component of musk, is known for its significant pharmacological properties. However, its clinical application is limited due to poor water solubility and moderate stability. This study aims to address these limitations by encapsulating MUS within biodegradable γ-cyclodextrin metal–organic frameworks (γ-CD-MOFs) using a solvent-free method to enable oral MUS delivery by improving solubility and stability, pending in vivo validation. Methods: MUS was encapsulated into γ-CD-MOFs using a solvent-free method, achieving an optimal loading rate of 10.6 ± 0.7%. Comprehensive characterization was performed using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Biocompatibility was assessed using RAW264.7 cells, and molecular dynamics simulations were conducted to study the interactions between MUS and γ-CD-MOFs. Results: Characterization techniques confirmed the successful encapsulation of MUS into γ-CD-MOFs. Biocompatibility studies revealed no cytotoxicity, indicating that the system is safe for drug delivery. Molecular dynamics simulations showed that MUS preferentially occupies the large spherical cages of γ-CD-MOFs, driven by non-covalent interactions. Solubility tests and in vitro release studies demonstrated that the solubility of MUS was improved after encapsulation within γ-CD-MOFs. Stability assessments indicated that γ-CD-MOFs significantly enhanced the thermal and photostability of MUS, with high residual amounts remaining under various storage conditions. Conclusions: This study demonstrates the potential of γ-CD-MOFs to solidify MUS, enhance its solubility, and improve its storage stability, providing a foundation for its future use in pharmaceutical applications. Full article

Background/Objectives: Research on cyclodextrin-based metal-organic frameworks (CD-MOFs) is still in its infancy, but their potential for use in drug delivery—expressly in the lung—seems promising. We aimed to use the freeze-drying method to create a novel approach for preparing CD-MOFs. MOFs consisting of γ-cyclodextrin (γCD) and potassium cations (K⁺) were employed to encapsulate the poorly water-soluble model drug Ibuprofen (IBU) for the treatment of cystic fibrosis (CF). Methods: Using the LeanQbD^® software (v2022), we designed the experiments based on the Quality by Design (QbD) concept. According to QbD, we identified the three most critical factors, which were the molar ratio of the IBU to the γCD, incubation time, and the percentage of the organic solvent. light-, scanning electron microscope (SEM) and laser diffraction were utilized to observe the morphology and particle size of the samples. In addition, the products were characterized by Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Results: Based on characterizations, we concluded that a γCD-MOF/IBU complex was also formed using the freeze-drying method. Using formulations with optimal aerodynamic properties, we achieved 38.10 ± 5.06 and 47.18 ± 4.18 Fine Particle Fraction% (FPF%) based on the Andersen Cascade Impactor measurement. With these formulations, we achieved a fast dissolution profile and increased IBU solubility. Conclusions: This research successfully demonstrates the innovative use of freeze-drying to produce γCD-MOFs for inhalable IBU delivery. The method enabled to modify the particle size, which was crucial for successful pulmonary intake, emphasizing the need for further investigation of these formulations as effective delivery systems. Full article

Conventionally, methanol is the solvent of choice in the synthesis of gamma-cyclodextrin metal-organic frameworks (γ-CD-MOFs), but using ethanol as a replacement could allow for a more food-grade synthesis condition. Therefore, the aim of the study was to compare the γ-CD-MOFs synthesised with both methanol and ethanol. The γ-CD-MOFs were characterised by scanning electron microscopy (SEM), surface area and pore measurement, Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction (PXRD). The encapsulation efficiency (EE) and loading capacity (LC) of the γ-CD-MOFs were also determined for curcumin, using methanol, ethanol and a mixture of the two as encapsulation solvent. It was found that γ-CD-MOFs synthesised by methanol and ethanol do not differ greatly, the most significant difference being the larger crystal size of γ-CD-MOFs crystallised from ethanol. However, the change in solvent significantly influenced the EE and LC of the crystals. The higher solubility of curcumin in ethanol reduced interactions with the γ-CD-MOFs and resulted in lowered EE and LC. This suggests that different solvents should be used to deliberately manipulate the EE and LC of target compounds for better use of γ-CD-MOFs as their encapsulating and delivery agents. Full article

The important role of gasotransmitters in physiology and pathophysiology suggest employing gasotransmitters for biomedical treatment. Unfortunately, the difficulty in storage and controlled delivery of these gaseous molecules hindered the development of effective gasotransmitters-based therapies. The design of a safe, facile, and wide-scale method to delivery multiple gasotransmitters is a great challenge. Herein, we use an ultrasonic assisted preparation γ-cyclodextrin metal organic framework (γ-CD-MOF) as a broad-spectrum delivery vehicle for various gasotransmitters, such as SO₂, NO, and H₂S. The release rate of gasotransmitters could be tuned by modifying the γ-CD-MOF with different Pluronics. The biological relevance of the exogenous gasotransmitters produced by this method is evidenced by the DNA cleavage ability and the anti-inflammatory effects. Furthermore, the γ-CD-MOF composed of food-grade γ-CD and nontoxic metal salts shows good biocompatibility and particle size (180 nm). Therefore, γ-CD-MOF is expected to be an excellent tool for the study of co-delivery and cooperative therapy of gasotransmitters. Full article

Metal-organic frameworks based on cyclodextrins (CDs) have been proposed as promising drug delivery systems due to their large surface area, variable pore size, and biocompatibility. In the current work, we investigated an incorporation of tolfenamic acid (TA), a representative of non-steroidal anti-inflammatory drugs (NSAIDs), in a metal-organic framework based on γ-cyclodextrin and potassium cations (γCD-MOF). Composites γCD-MOF/TA obtained by absorption and co-crystallization methods were characterized using powder X-ray diffraction, low temperature nitrogen adsorption/desorption, scanning electron microscopy, and FTIR spectroscopy. It was demonstrated that TA loaded in γCD-MOF has an improved dissolution profile. However, the inclusion of TA in γ-CD reduces the membrane permeability of the drug. A comparative analysis of the encapsulation of different NSAIDs in γCD-MOF was performed. The impact of NSAID structure on the loading capacity was considered for the first time. It was revealed that the presence of heterocycles in the structure and drug lipophilicity influence the loading efficiency of NSAIDs in γCD-MOF. Full article

Thymol is a phenol monoterpene with potential antifungal, antioxidant and antibacterial activities. Due to the low water solubility and high volatility of thymol, encapsulation serves as an effective tool during application. In the present study, cyclodextrin (CD)-based metal-organic-frameworks (MOFs) were synthesized using α-CD, β-CD, and γ-CD as organic building blocks, and further complexed with thymol to produce three CD-MOF-THY inclusion complexes (ICs). The encapsulation content, release kinetics and fruit preservation effect of ICs were analyzed. Results showed that thymol was well embedded in γ-CD-MOFs, with the highest encapsulation content of 286.7 ± 8.4 mg/g. Release kinetics revealed that CD-MOFs exhibited a controlled release effect toward thymol for 35 days. The release kinetics of three ICs fit the Rigter–Peppas model well, with γ-CD-MOF-THY showing the lowest release rate constant of 2.85 at 50 °C, RH 75%. Moreover, γ-CD-MOF-THY exhibited a remarkable preservation performance on cherry tomatoes with the lowest decay index (18.75%) and weight loss (5.17%) after 15 days of storage, suggesting this material as a potential fresh-keeping material for fruit and vegetable preservation. Full article

Modified γ-cyclodextrin metal organic frameworks (γ-CD-MOFs) are a promising eco-friendly sorbents for post-combustion CO₂ capture. Polyethyleneimine (PEI) has been widely used for modifying MOFs to enhance their CO₂ sorption capacity and selectivity through the introduction of CO₂ selective amine groups. The main objective of this study was to determine the optimal PEI molecular weight and arrangement (linear or branched) to enhance γ-CD-MOF’s CO₂ sorption capacity. γ-CD-MOFs were impregnated with linear as well as branched PEI with molecular weights of 600, 1200 or 10,000. The CO₂ sorption capacity of the PEI-impregnated γ-CD-MOFs was determined using a quartz crystal microbalance assembly at CO₂ partial pressures from 0.35–1.0 atm. Impregnation with 600 g/mole branched PEI achieved the highest CO₂ sorption capacity of 0.9 mmole/g CO₂ at 1 atm, followed by the linear PEI (0.12 mmol/g). Modification with the other branched PEI molecular weights did not achieve detectable CO₂ sorption, likely because of pore blockage with the relatively larger PEI molecular weights, as demonstrated by molecular docking simulations. Furthermore, the control γ-CD-MOFs did not sorb CO₂, likely because of the lower attraction forces between CO₂ and the large pore volume of the unmodified MOFs. Full article

Cyclodextrin-based metal–organic frameworks-1 (CD-MOF-1) prepared using potassium hydroxide, ethanol, and γ-cyclodextrin (γ-CD) has been reported as a new type of MOF for the development of pharmaceutical formulations. The present study aimed to investigate the physicochemical properties of ascorbic acid derivatives (L-ascorbyl 6-palmitate (ASCP); L-ascorbyl 2,6-palmitate (ASCDP)) complexed with CD-MOF-1 by a solvent evaporation method. Powder X-ray diffraction revealed that the crystal diffraction pattern of CD-MOF-1 changed from α-type to β-type when prepared by a solvent evaporation method. For ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4 evaporated samples, the crystal diffraction peaks derived from ASCP and ASCDP disappeared, indicating a β-like behavior. Differential scanning calorimetry results revealed that the endothermic peaks of evaporated samples (ASCP/CD-MOF-1 = 1/2 and ASCDP/CD-MOF-1 = 1/4) were not detected due to melting. Furthermore, intermolecular interactions were observed in the hydrogen bonds between the CH groups of the side chains of ASCP and ASCDP and the OH group of CD-MOF-1 in (ASCP/CD-MOF-1 = 1/2) and EVP (ASCDP/CD-MOF-1 = 1/4), based on the near-infrared absorption spectroscopy analysis. CD-MOF-1 did not form inclusion complexes with the lactone rings of ASCP and ASCDP, but with the lipophilic side chains. These results suggested that CD-MOF-1 may be useful in preparing novel drug carriers for ASCP and ASCDP. Full article

Recently developed, nanoscale metal-organic frameworks (nanoMOFs) functionalized with versatile coatings are drawing special attention in the nanomedicine field. Here we show the preparation of core–shell MIL-100(Al) nanoMOFs for the delivery of the anticancer drug doxorubicin (DOX). DOX was efficiently incorporated in the MOFs and was released in a progressive manner, depending on the initial loading. Besides, the coatings were made of biodegradable γ-cyclodextrin-citrate oligomers (CD-CO) with affinity for both DOX and the MOF cores. DOX was incorporated and released faster due to its affinity for the coating material. A set of complementary solid state nuclear magnetic resonance (ssNMR) experiments including ¹H-¹H and ¹³C-²⁷Al two-dimensional NMR, was used to gain a deep understanding on the multiple interactions involved in the MIL-100(Al) core–shell system. To do so, ¹³C-labelled shells were synthesized. This study paves the way towards a methodology to assess the nanoMOF component localization at a molecular scale and to investigate the nanoMOF physicochemical properties, which play a main role on their biological applications. Full article

Cyclodextrin (CD) has been used to prepare biocompatible and nontoxic metal-organic frameworks (MOFs) suitable for biomedical applications as drug carriers. In this study, γ-CD/K-based MOF (γ-CD-MOF-1-α) was synthesized and its stability in various solvents was explored by single-crystal X-ray diffractometry (SCXRD) and powder X-ray diffractometry (PXRD). As a result of solvent-induced phase transformations, two novel crystalline phases of γ-CD-MOF-1 were discovered. The newly formed ε- and δ-phases crystallize in orthorhombic and tetragonal symmetry, respectively. In ε-phase, toluene was determined as a guest molecule by SCXRD. Interactions between γ-cyclodextrin and solvent molecules in ε-phase were evaluated using Hirshfeld surface analysis. The thermal stability of the new crystal forms of γ-CD-MOF-1 was analyzed by differential scanning calorimetry and thermogravimetric analysis. Full article