Cyclodextrin-based Metal-organic Frameworks Research Articles

Sustained-Release Hydrogen-Powered Bilateral Microneedles Integrating CD-MOFs for In Situ Treating Allergic Rhinitis.

Glucocorticoids are widely used for treating allergic rhinitis, but conventional intranasal administration encounters unfavorable nasal cilia clearance and nasal mucosal barrier. Herein, a bilateral microneedle patch is fabricated for delivering cyclodextrin-based metal-organic frameworks (CD-MOF) encapsulating dexamethasone (DXMS) and paeonol (Pae), while NaH particles are mounted on the basal part of each microneedle. By intranasal administration, the microneedles are propelled into the nasal mucosa by NaH-generated hydrogen and then swell to form a hydrogel for sustainedly releasing drugs. The DXMS/Pae combination is demonstrated to be superior to more than the twofold dose of DXMS alone for improving allergic rhinitis in rats. It involves reducing mast cell degranulation and modulating Treg/Th17 cell homeostasis, whereas inhibiting Th1 to Th2 differentiation is associated with regulating the GATA3/T-bet pathway, as well as repairing epithelial barrier function by increasing MUC1 and downregulating periostin. In addition, this delivery system modulates the lipid metabolism of the nasal mucosa. Notably, the newly designed device significantly enhances the drug's therapeutic effect, and NaH-generated hydrogen may have the potential adjunctive therapeutic effect. Collectively, such an emerging microneedle-mediated nasal drug delivery creates a new form for alleviating immune inflammation and contributes a promising solution to reduce clinical glucocorticoid abuse.

Cyclodextrin Metal-Organic Frameworks as a Drug Delivery System for Selected Active Pharmaceutical Ingredients.

The cyclodextrin-based metal-organic frameworks (CD MOFs) are a suitable molecular platform for drug delivery systems of various active pharmaceutical ingredients (APIs). The low toxicity and cost-efficient synthesis make CD MOFs an attractive host for the encapsulation of APIs. In this study, we created a model system based on γCD-K MOFs with widely used drugs carmofur (HCFU), 5-fluorouracil (5-FU), and salicylic acid (HBA) to study host-guest encapsulation methods using different crystallization protocols. The host-guest complexes of API:CD MOF in an in-depth study were investigated by liquid chromatography-mass spectrometry (LC-MS), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and 19F- and 13C-detected solid-state NMR spectroscopy (ssNMR). These techniques confirmed the structure and interaction sites within the encapsulation product in the host-guest complex. We also evaluated the toxicity and biocompatibility of the API:CD MOF complex using in vitro and in vivo methods. The cytotoxicity, hepatotoxicity, and neurotoxicity were established with cell lines of fibroblasts (BJ), human liver cell line (HepG2), and human oligodendrocytic cells (MO3.13). Then, Danio rerio was used as an in vivo experimental model of ecotoxicity. The results showed the choice of γCD-K-5 as the most protective and safe option for drug encapsulation to decrease its toxicity level against normal cells.

Microneedle-mediated nose-to-brain drug delivery for improved Alzheimer's disease treatment

Conventional transnasal brain-targeted drug delivery strategies are limited by nasal cilia clearance and the nasal mucosal barrier. To address this challenge, we designed dissolving microneedles combined with nanocarriers for enhanced nose-to-brain drug delivery. To facilitate transnasal administration, a toothbrush-like microneedle patch was fabricated with hyaluronic acid-formed microneedles and tannic acid-crosslinked gelatin as the base, which completely dissolved in the nasal mucosa within seconds leaving only the base, thereby releasing the loaded cyclodextrin-based metal-organic frameworks (CD-MOFs) without affecting the nasal cilia and nasal microbial communities. As nanocarriers for high loading of huperzine A, these potassium-structured CD-MOFs, reinforced with stigmasterol and functionalized with lactoferrin, possessed improved physical stability and excellent biocompatibility, enabling efficient brain-targeted drug delivery. This delivery system substantially attenuated H2O2- and scopolamine-induced neurocyte damage. The efficacy of huperzine A on scopolamine- and D-galactose & AlCl3-induced memory deficits in rats was significantly improved, as evidenced by inhibiting acetylcholinesterase activity, alleviating oxidative stress damage in the brain, and improving learning function, meanwhile activating extracellular regulated protein kinases-cyclic AMP responsive element binding protein-brain derived neurotrophic factor pathway. Moreover, postsynaptic density protein PSD-95, which interacts with two important therapeutic targets Tau and β-amyloid in Alzheimer's disease, was upregulated. This fruitful treatment was further shown to significantly ameliorate Tau hyperphosphorylation and decrease β-amyloid by ways including modulating beta-site amyloid precursor protein cleaving enzyme 1 and a disintegrin and metalloproteinase 10. Collectively, such a newly developed strategy breaks the impasse for efficient drug delivery to the brain, and the potential therapeutic role of huperzine A for Alzheimer's disease is further illustrated.

Encapsulation Alleviates the Auto-browning of Epigallocatechin-3-gallate in Aqueous Solutions through Regulating Molecular Self-Aggregation Behavior.

Catechins are widely recognized for superb antioxidant capability, but their application as food antioxidants is hindered by susceptibility to auto-browning under high-moisture conditions. Here, we proposed a strategy of ordered encapsulation with cyclodextrin-based metal-organic frameworks (CD-MOFs) to alleviate the auto-browning phenomenon of catechins while preserving their antioxidant capability and demonstrated the feasibility of this strategy via selecting epigallocatechin-3-gallate (EGCG) as a model. Even in aqueous solutions, EGCG@CD-MOFs still possessed delayed browning, in contrast with pristine EGCG, characterized by suppressed efficiencies on the generation of oxidative dimers (theasinensin A) and semiquinone radicals. Mechanism insights revealed that ordered encapsulation brought dual regulations on the self-aggregation behavior of EGCG: EGCG@CD-MOFs exhibited a gradual structural collapse from the framework toward irregular aggregates as O-K bonds broke progressively, which restricted molecular mobility of EGCG, and EGCG molecular conformations became constrained by the structure of EGCG@CD-MOFs as well as rich intermolecular forces, even after structural collapse.

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

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.

In Situ Growth of Cyclodextrin‐Based Metal Organic Framework Air Filters for Reusable SO2 Adsorbent Applications

AbstractIn situ growth of cyclodextrin‐based metal‐organic frameworks (CD‐MOFs) is investigated for the effective fabrication of MOF composites through the vapor diffusion method combined with O2 plasma treatment. The growth rate of γ‐CD‐MOFs on poly(ethylene terephthalate) fibers (CD‐MOFs–PET) is determined for 136 h, and the CD‐MOFs‐PET with 24 h growth time shows the highest surface area without crystal deformation. The specific surface area of the CD‐MOFs‐PET with 24 h growth time is 142.88 m2 g−1, which is 235 times higher than the pristine PET fibers. The 24 h CD‐MOFs‐PET shows removal efficiencies higher than 99% for PM0.1 and higher than 95% for SO2 gas. The CD‐MOFs‐PET demonstrates high recovery of SO2 adsorption ability by the repeated adsorption‐desorption cycles, maintaining up to 90% of initial adsorption performance. This study intends to provide an informative discussion of the applicability of textile‐based CD‐MOFs and the development of reusable filters for the removal of SO2.

The Emerging Role of Cyclodextrin Metal–Organic Frameworks in Ostheotherapeutics

Metal–Organic Frameworks (MOFs) are a class of coordination compounds with high versatility of design and a high loading ability. These properties have made them increasingly attractive for drug delivery, with research focusing mostly on the preparation of biocompatible MOFs. A suitable strategy is the use of cyclodextrins, cyclic oligosaccharides with excellent biosafety profiles. This review summarises the early steps taken in the application of cyclodextrin-coated and cyclodextrin-based MOFs in the treatment of bone-related diseases divided into three categories: cyclodextrin-coated MOFs, cyclodextrin-based MOFs and cross-linked derivatives of CD-MOFs. Applications in the delivery of bisphosphonates, osteoporotic regulating drugs and non-steroidal anti-inflammatory drugs, for osteoarthritis management, are highlighted. Lastly, the use of these materials in dentistry is exemplified with a recent report.

Cyclodextrin-Based Metal-Organic Frameworks as Efficient Carriers for Trans-N-P-Coumaroyltyramine: Study of Solubilization Effect, Drug Stability and Inhibitory Activity on Α-Glucosidase

Cyclodextrin-Based Metal-Organic Frameworks as Efficient Carriers for Trans-N-P-Coumaroyltyramine: Study of Solubilization Effect, Drug Stability and Inhibitory Activity on Α-Glucosidase

Tunable arrangement of hydrogel and cyclodextrin-based metal organic frameworks suitable for drug encapsulation and release

The present study focused on the integration of beta-cyclodextrin based metal-organic frameworks (β-CDMOF) with polymer to obtain hybrid materials with advantageous properties compared to traditional single-component polymers or metal-organic frameworks (MOF) matrixes. We fabricated two complexes with different morphology and structure. During the in situ growth of β-CDMOF around the hydrogel, potassium ions on polysaccharides gradually dissociated to participate in the growth of crystals, while other potassium ions on the carboxylic acid groups provided bridges between crystals and hydrogel, forming a necklace-shaped complex (SHPs@β-CDMOF). Hydrogen bonding and coordination interactions between β-CDMOF and hydrogel are present in a dendritic sandwich-shaped complex (β-CDMOF@SHPs). Furthermore, using the hydrophobic molecule curcumin as a model drug, we have demonstrated that SHPs@β-CDMOF and β-CDMOF@SHPs hybrid materials stabilize the included drug and have potential for controlled drug release. Collectively, the integration of MOF with polymer holds a great promise for drug delivery applications.

Ru(bpy)32+ encapsulated cyclodextrin based metal organic framework with improved biocompatibility for sensitive electrochemiluminescence detection of CYFRA21-1 in cell

Metal-organic frameworks (MOFs) have attracted strong interest from researchers. Here, for the first time, we report a sandwich-type electrochemiluminescent biosensor as a signal probe prepared from cyclodextrin-based MOF (CD-MOF)-encapsulated Ru(bpy)32+. Due to the combination of the two materials, the obtained CD-MOF@Ru(bpy)32+ nanocomposites exhibited excellent biocompatibility and electrochemical performance. At the same time, CD-MOF@Ru(bpy)32+ adhered to the electrode surface closely because Ru(bpy)32+ was successfully encapsulated by the CD-MOF. In this paper, CD-MOF@Ru(bpy)32+ and glutaraldehyde were modified on a glassy carbon electrode (GCE) surface to provide excellent conductivity and to immobilize primary antibodies. Under the optimal experimental conditions, the established biosensor exhibited high sensitivity, a low limit of detection and a great linear range for cytokeratin 19 fragment antigen 21-1 (CYFRA21-1). Finally, this designed biosensor was further applied to the determination of CYFRA21-1 in A549 lung cancer cells. According to the results of the toxicity test, CD-MOF@Ru(bpy)32+ exhibited hypotoxicity to living bodies. These results all indicate that this biosensor has great potential for a promising approach to the evaluation of biomarkers.

Cyclodextrin Metal-Organic Frameworks and Their Applications.

Cyclodextrin-based metal-organic frameworks (CD-MOFs), derived from γ-cyclodextrin (γ-CD) and alkali metal cations, constitute a class of porous, renewable, and edible MOFs that can be synthesized from a naturally occurring carbohydrate on a large scale. γ-CD is a C8-symmetrical cyclic oligosaccharide composed of eight asymmetric α-1,4-linked d-glucopyranosyl residues that possesses a bucket-shaped cavity with an inner diameter of ∼1 nm and a depth of ∼0.8 nm. Upon combination of 1 equiv of γ-CD with 8 equiv of potassium hydroxide in an aqueous solution, followed by vapor diffusion of MeOH (or EtOH) into this solution during several days, CD-MOF-1 is obtained as cubic crystals. This carbohydrate-based MOF, which was discovered serendipitously in 2010, was the first highly crystalline CD-MOF to be obtained. X-ray crystallography of a single crystal reveals that it adopts the space group I432 with unit cell dimensions of approximately 31 × 31 × 31 Å3. Other CD-MOFs, namely, CD-MOF-2 and CD-MOF-3, can be obtained when potassium ions are replaced by rubidium and cesium ions, respectively. CD-MOFs comprise extended body-centered frameworks of (γ-CD)6 cubic units, which contain spherical pores that reside at the center of the cubes, interconnected by alkali metal cations, forming both cylindrical and triangular channels.During the past decade, CD-MOFs have emerged as a useful class of multifunctional materials based on porous frameworks with extended structures displaying robust crystallinity, permanent porosity, and excellent biocompatibility. The family of CD-MOFs has been joined by a growing collection of metal nodes involving alkali metal cations (Li+, Na+, K+, Rb+, Cs+) and γ-CD as well as its derivatives. As a result of the ability of their extended porous frameworks to absorb guest molecules, including gases, drugs, metal-based nanoclusters, and nanoparticles, CD-MOFs have potential applications in areas as disparate as templating syntheses of metal-based nanoparticles and gels, adsorption and separation, trapping highly reactive intermediates, catalyst supports, sensing, electrical memory, and drug delivery.In this Account, we tell the story of CD-MOFs, a scientific discovery made in our research laboratory at Northwestern University, and the opportunities to use these environmentally friendly porous materials across different fields of science and technology. The story includes representative synthetic protocols for the preparation of CD-MOFs, along with an overview of their structural features, functionalization, and chemical modification aimed at increasing their stabilities in aqueous environments, and finally, a summary of their applications. The examples we will discuss, however, are only illustrative, and there is a significant body of additional findings emanating from our laboratory and others, especially in the realm of developing new synthetic strategies, tuning the framework stabilities, and exploring the guest inclusion and emergent properties of CD-MOFs. We refer readers to the original communications, papers, and reviews cited herein. We hope that, in the telling of the story of CD-MOFs, this Account may promote new scientific discoveries and further development of CD-MOF-based technologies in the future.

Cyclodextrin-based metal-organic frameworks for pulmonary delivery of curcumin with improved solubility and fine aerodynamic performance.

Pulmonary drug delivery has attracted considerable attention in recent years. However, it is still a major challenge to deliver poorly water-soluble drugs to lungs with good solubility and fine aerodynamic performance. In this study, curcumin was loaded into cyclodextrin-based metal-organic frameworks (CD-MOFs) for pulmonary delivery. Compared with micronized curcumin prepared by jet milling, curcumin-loaded CD-MOFs (Cur-CD-MOFs) exhibited excellent aerodynamic performance, which was attributed to the unique porous structure and lower density of CD-MOFs. The dissolution test showed that the drug release rate of Cur-CD-MOFs was much faster than that of micronized curcumin. The all-atom molecular dynamic simulation showed that curcumin molecules were loaded into the hydrophobic cavities of CD-MOFs or entered into the large hydrophilic cavities to form nanoclusters. The elevated wettability of Cur-CD-MOFs and the unique spatial distribution feature of curcumin in porous interior of CD-MOFs might be favorable for the improved dissolution rate. The DPPH radical scavenging test showed that Cur-CD-MOFs had prominent antioxidant activities. Therefore, CD-MOFs were expected to be promising carriers for pulmonary delivery of poorly water-soluble drugs.

Improvement of the stabilities and antioxidant activities of polyphenols from the leaves of Chinese star anise (Illicium verum Hook. f.) using β-cyclodextrin-based metal-organic frameworks.

Polyphenols extracted from plants are usually highly unstable and rapidly transformed into various reaction products during food and drug processing, thus limiting their applications. To improve the stability and solubility of polyphenols from the leaves of Chinese star anise (Illicium verum Hook. f.), and hence to expand their application to food and medicine, the extracted anise leaf polyphenols (ALPs) were microencapsulated using β-cyclodextrin (β-CD) and cyclodextrin-based metal-organic frameworks (β-CD-MOFs). The optimum inclusion rate of ALP/β-CD-MOFs was 97.80% at a core-wall ratio of 1:10. Meanwhile, the stabilities, solubilities and antioxidant activities of the polyphenols before and after inclusion were compared. The results showed both the stabilities and solubilities of ALP/β-CD-MOFs were significantly improved compared with those of ALPs and ALP/β-CD, suggesting the potential of β-CD-MOFs as newer and better carriers than β-CD for polyphenols in food industry applications. The free radical (including superoxide, hydroxyl and DPPH radicals) scavenging activities were also improved by microencapsulation. Superoxide radical scavenging reaction also showed slow-release property of ALP/β-CD-MOFs. The formation of the inclusion complex was further confirmed using Fourier transform infrared spectral characterization. Microencapsulation with β-CD-MOFs could expand the application scope of ALPs, and it is more effective than encapsulation with β-CD. This is important for a better understanding and application of this useful traditional Chinese plant. As a new material with high efficiency and edibility, β-CD-MOFs are not limited to the chemical field, but also have potential in new areas of food, medicine and healthcare products. © 2020 Society of Chemical Industry.

Biocompatible Cyclodextrin-Based Metal–Organic Frameworks for Long-Term Sustained Release of Fragrances

The encapsulation of volatile fragrances within porous materials is capable of increasing their stability for long-term controlled release; however, the introduction of low biocompatible carrier ma...

Glutathione responsive cubic gel particles cyclodextrin metal-organic frameworks for intracellular drug delivery

Novel cubic gel particles (ssCGP) with Glutathione (GSH) triggered drug release features were prepared by crosslinking the cyclodextrin based metal-organic frameworks (CD-MOFs) templets with a newly synthesized biodegradable disulfide bond-bearing linker and removing of the potassium ion in sequence. The morphology and size of ssCGP were investigated by field emission scanning electron microscope (FESEM) and dynamic light scattering. Energy dispersive x-ray spectroscopy (EDX), fourier transform infrared spectroscopy (FT-IR), powder x-ray diffraction (PXRD) and Brunauer-Emmett-Teller (BET) were employed to characterize the structure of ssCGP. ssCGP have regular hexahedron shape with edge length about 200–400 nm. Excellent ability of drug adsorption was achieved by using doxorubicin (DOX) as a model drug. The GSH triggered drug release of ssCGP was observed both in GSH contained solutions and intracellular environments. ssCGP have been demonstrated as a biocompatible porous nanocarrier, particular for intracellular drug delivery.

Synergistic antioxidant activity and anticancer effect of green tea catechin stabilized on nanoscale cyclodextrin-based metal–organic frameworks

Green tea catechins have received significant attention due to their potent antioxidant activity as well as diverse biological properties. Stabilizing and protecting catechins from degradation is very important but challenging. In this work, a nanosized edible γ-cyclodextrin-based metal–organic framework (CD-MOF) was designed and fabricated by a facile vapor diffusion route and applied for the encapsulation of a model green tea catechin, (-)-epigallocatechin gallate (EGCG) for the first time. Downsizing CD-MOF to the nanoscale is a suitable method to tackle down new applications. Significantly, the antioxidant activity results show that the CD-MOF-EGCG can remarkably enhance the antioxidant activity in alkaline solutions, as compared to that of free EGCG. Furthermore, the prepared CD-MOF-EGCG showed strong cancer cell growth inhibitory effects on C6 cells as confirmed by the cell viability assay. This work demonstrates that such safe and nontoxic nanoscale CD-MOF-based porous materials hold great promise for applications in the field of stabilization of catechins for biomedical applications.

Uniform and directional growth of centimeter-sized single crystals of cyclodextrin-based metal organic frameworks

Although macroscopically-sized MOF crystals have proven of interest for efficient chromatographic separations, information processing, or optoelectronic devices, growing really large crystals has proven problematic. A growth-and-reseeding method can now produce MOF monocrystals ca. 1 cm3 in volume vs. at most ca. 0.025 cm3 by prior methods.

Recent progress in the synthesis, structural diversity and emerging applications of cyclodextrin-based metal-organic frameworks.

Inorganic-organic hybrid materials, especially metal-organic frameworks (MOFs) composed of metals and organic linkers, have emerged as a new class of versatile materials owing to their tunable structure and controllable functionality. As typical biocompatible MOFs, cyclic oligosaccharide cyclodextrin-based carbohydrate metal-organic frameworks (CD-MOFs) have recently attracted considerable attention due to their edible, renewable and biodegradable nature. Herein, we focus on the latest advances concerning these materials. First, the synthesis methods and structural diversity of CD-MOFs are introduced and summarized. Besides, the synthetic strategies of moisture-resistant CD-MOFs are also emphasized. Moreover, their applications, including gas adsorption, separation, sensing, memristor fabrication, as templates in nanoparticle synthesis, light emission and especially drug delivery, are systematically discussed and highlighted. Finally, to conclude the review, some insights and current challenges that need to be addressed for the further development of these materials are proposed. We anticipate that this review will result in a better understanding of CD-MOFs and will help maximize the potential functions of these materials.

Cyclodextrin-Based Metal-Organic Frameworks (CD-MOFs) in Pharmaceutics and Biomedicine.

Metal-organic frameworks (MOFs) show promising application in biomedicine and pharmaceutics owing to their extraordinarily high surface area, tunable pore size, and adjustable internal surface properties. However, MOFs are prepared from non-renewable or toxic materials, which limit their real-world applications. Cyclodextrins (CDs) are a typical natural and biodegradable cyclic oligosaccharide and are primarily used to enhance the aqueous solubility, safety, and bioavailability of drugs by virtue of its low toxicity and highly flexible structure, offering a peculiar ability to form CD/drug inclusions. A sophisticated strategy where CD is deployed as a ligand to form an assembly of cyclodextrin-based MOFs (CD-MOFs) may overcome real-world application drawbacks of MOFs. CD-MOFs incorporate the porous features of MOFs and the encapsulation capability of CD for drug molecules, leading to outstanding properties when compared with traditional hybrid materials. This review focuses on the inclusion technology and drug delivery properties associated with CD-MOFs. In addition, synthetic strategies and currently developed uses of CD-MOFs are highlighted as well. Also, perspectives and future challenges in this rapidly developing research area are discussed.

Characterization and Mechanisms of Novel Emulsions and Nanoemulsion Gels Stabilized by Edible Cyclodextrin-Based Metal-Organic Frameworks and Glycyrrhizic Acid.

In this study, a novel emulsion stabilized by nano-cyclodextrin-based metal-organic frameworks and glycyrrhizic acid (CD-MOF/GA) was successfully fabricated, exhibiting long-term storage stability. The characterization and mechanisms for the emulsion formation with CD-MOF/GA were studied. The phase change of the emulsions from sol to gel could be controlled using different oil fractions and mass ratios of CD-MOF and GA. The rheological results showed that the emulsions were transformed from liquid emulsions to emulsion gels when the oil fractions were higher than 0.3 and the mass ratio of CD-MOF and GA was 1:3. The low-field nuclear magnetic resonance results revealed that the T22 relaxation time of emulsions decreased from 403.702 to 231.013 ms when the oil fractions increased from 0.1 to 0.6, indicating that movable water was converted to constructal water. The emulsions showed good stability, even in high-alkaline pH and high-temperature conditions.