In Vitro and In Silico Study on the Molecular Encapsulation of α-Tocopherol in a Large-Ring Cyclodextrin.

α-tocopherol is the physiologically most active form of vitamin E, with numerous biological activities, such as significant antioxidant activity, anticancer capabilities, and anti-aging properties. However, its low water solubility has limited its potential use in the food, cosmetic, and pharmaceutical industries. One possible strategy for addressing this issue is the use of a supramolecular complex with large-ring cyclodextrins (LR-CDs). In this study, the phase solubility of the CD26/α-tocopherol complex was investigated to assess the possible ratios between host and guest in the solution phase. Next, the host-guest association of the CD26/α-tocopherol complex at different ratios of 1:2, 1:4, 1:6, 2:1, 4:1, and 6:1 was studied by all-atom molecular dynamics (MD) simulations. At 1:2 ratio, two α-tocopherol units interact spontaneously with CD26, forming an inclusion complex, as supported by the experimental data. In the 2:1 ratio, a single α-tocopherol unit was encapsulated by two CD26 molecules. In comparison, increasing the number of α-tocopherol or CD26 molecules above two led to self-aggregation and consequently limited the solubility of α-tocopherol. The computational and experimental results indicate that a 1:2 ratio could be the most suitable stoichiometry to use in the CD26/α-tocopherol complex to improve α-tocopherol solubility and stability in inclusion complex formation.

Cyclodextrin-Based Displacement Strategy of Sterigmatocystin from Serum Albumin as a Novel Approach for Acute Poisoning Detoxification.

This study demonstrates that sterigmatocystin (STC) interacts non-covalently with various cyclodextrins (CDs), showing the highest binding affinity for sugammadex (a γ-CD derivative) and γ-CD, and an almost order of magnitude lower affinity for ß-CD. This difference in affinity was studied using molecular modelling and fluorescence spectroscopy, which demonstrated a better insertion of STC into larger CDs. In parallel, we showed that STC binds to human serum albumin (HSA) (a blood protein known for its role as a transporter of small molecules) with an almost two order of magnitude lower affinity compared to sugammadex and γ-CD. Competitive fluorescence experiments clearly demonstrated an efficient displacement of STC from the STC-HSA complex by cyclodextrins. These results are a proof-of-concept that CDs can be used to complex STC and related mycotoxins. Similarly, as sugammadex extracts neuromuscular relaxants (e.g., rocuronium and vecuronium) from blood and blocks their bioactivity, it could also be used as first aid upon acute intoxication to encapsulate a larger part of the STC mycotoxin from serum albumin.

Cyclodextrin-enabled nepafenac eye drops with improved absorption open a new therapeutic window.

Nepafenac is a highly effective NSAID used for treating postoperative ocular inflammation and pain after cataract surgery and its advantage over conventional topical NSAIDs has been proved many times. However, Nevanac® is a suspension eye drop, which clearly lacks patient compliance causing irritation, blurred vision, foreign body sensation along with problematic dosage due to its sticky, inhomogeneous consistence. In this study, nepafenac containing eye drops were prepared using hydroxypropyl-ß-cyclodextrin to ensure complete dissolution of nepafenac, sodium hyaluronate to provide mucoadhesion and adequate viscosity and a preservative-free officinal formula, Oculogutta Carbomerae containing carbomer (just like Nevanac®), therefore providing a similar base for the new formulations. According to an experimental design, 11 formulations were tested in vitro including two reference formulations by measuring their viscosity, mucoadhesion, drug release and corneal permeability. Finally, two formulations were found promising and investigated further on porcine eyes ex vivo and corneal distribution of nepafenac was determined by RAMAN mapping. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose were ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.

A comparative study on inclusion complex formation between formononetin and ß-cyclodextrin derivatives through multiscale classical and umbrella sampling simulations.

Formononetin, a naturally occurring isoflavone exhibits a wide range of therapeutic applications including antioxidant, anti-tumor, antiviral, anti-diabetic and neuroprotective activities. However, the low hydro-solubility of formononetin has limited its prospective use in cosmetic, neutraceutical and pharmaceutical industries. Cyclodextrins (CDs), especially ß-CD and its derivatives have emerged as promising agents to improve the water solubility of poorly hydrosoluble compounds by the formation of inclusion complexes. We employed multiscale (1000 ns) explicit solvent and umbrella sampling molecular dynamics (MD) simulations to study the interactions and thermodynamic parameters of inclusion complex formation between formononetin and five most commonly used ß-CD derivatives. Classical MD simulations revealed two possible binding conformations of formononetin inside the central cavity of hydroxypropyl-ß-CD (HP-ß-CD), randomly methylated-ß-CD (ME-ß-CD), and sulfobutylether-ß-CD (SBE-ß-CD). The binding conformation with the benzopyrone ring of formononetin inside the central cavity of ß-CD derivatives was more frequent than the phenyl group occupying the hydrophobic cavity. These interactions were supported by a variety of non-bonded contacts including hydrogen bonds, pi-lone pair, pi-sigma, and pi-alkyl interactions. Formononetin showed favorable end-state MD-driven thermodynamic binding free energies with all the selected ß-CD derivatives, except succinyl-ß-CD (S-ß-CD). Furthermore, umbrella sampling simulations were used to investigate the interactions and thermodynamic parameters of the host-guest inclusion complexes. The SBE-ß-CD/formononetin inclusion complex showed the lowest binding energy signifying the highest affinity among all the selected host-guest inclusion complexes. Our study could be used as a standard for analyzing and comparing the ability of different ß-CD derivatives to enhance the hydro-solubility of poorly soluble molecules.

Electrospinning of Cyclodextrin-Oligolactide Derivatives.

The materials used for the preparation of electrospun mats exhibit a large variety. Among them, cyclodextrins (CDs) and their derivatives have received thorough attention. Herein, we focus on the preparation of electrospun fibers based on biodegradable cyclodextrin-oligolactide (CDLA) derivatives, which may be qualified as polymer-free cyclodextrin. CDLA was prepared by ring opening of L-lactide initiated by the ß-cyclodextrin. A clear structural image of the high-purity CDLA product was proved by MALDI MS. Preparation of the electrospun mats was optimized by taking into consideration the electrospinning parameters such as applied voltage, needle-to-collector distance, flow rate, the concentration of cyclodextrin solutions, and solvent type. The obtained electrospun fibers were morphologically characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and small-angle X-ray scattering (SAXS). SEM allowed the optimization of the electrospinning process to obtain beadless fibers with submicronic diameters. Further analysis by TEM and SAXS revealed the inner structural features of the CDLA-based filaments. Our results showed that the high purity CDLA materials, structurally well-defined at the molecular level, are suitable for the preparation of electrospun mats by using dimethylformamide or a water/acetonitrile mixture as electrospinning solvents, similar to lower molecular weight commercial cyclodextrin derivatives.

Antibacterial drugs and cyclodextrin inclusion complexes: a patent review.

INTRODUCTION: Bacterial antibiotic resistance occurs when bacteria mutate and escape the effect of antibiotics, which makes the antibiotics no longer effective in treating infections. New solutions for bacterial infections are a persistent need including the identification of drugs with better pharmacological profiles, more potent, and safer. Cyclodextrins inclusion complexes have been able to improve the physicochemical and pharmacological properties of the formulation molecules, resulting in new alternatives with better efficacy. AREAS COVERED: The patents analyzed in the review used treatments based on antibiotics already on the market, natural products, and synthesized molecules composed of the formulation with cyclodextrins. The combination between cyclodextrin and nanostructures also were presented in the patents review process. Moreover, inclusion complexes have been an alternative in developing treatment mainly in China by the pharmaceutical industries in several countries such as Germany, Hungary, the United States of America, Japan and China. EXPERT OPINION: This review is broad and complete since it considers the first patent involving cyclodextrins and antibacterial drugs. Therefore, the various inclusion complexes and antibacterial drugs alternatives presented in this review offer therapeutic options to fight bacterial infections. If shown to be effective, these drugs may be extremely important in the current clinical practice.

Thiolated cyclodextrins: A comparative study of their mucoadhesive properties.

AIM: The aim of this study was the comparison of the mucoadhesive properties of nonionic, negatively, and positively charged thiolated cyclodextrins (CDs), including α-, ß-, and γ-CDs of low and high degree of thiolation. METHODS: Native α-, ß-, and γ-CDs were thiolated with phosphorous pentasulfide in sulfolane (CD-SH) (i), via reductive amination with cysteamine after oxidative ring opening (CD-Cya) (ii), and via esterification with mercaptosuccinic acid (CD-MSA) (iii). These thiolated CDs were characterized via 1H NMR and Ellman's test. Cytotoxicity was determined via resazurin and hemolysis assay. Mucoadhesive properties were evaluated via rheological studies with freshly isolated porcine mucus, as well as residence time studies on porcine small intestinal mucosa. RESULTS: The structure of thiolated CDs was confirmed via 1H NMR. The degree of thiolation was in the range of 594-1034 µmol/g for low and 1360-3379 µmol/g for high CD-SH, whereas thiolated CD-Cya and thiolated CD-MSA exhibited a degree of thiolation of 1142-3242 µmol/g and 243-1227 µmol/g, respectively. Just cationic CDs showed cytotoxicity. Nonionic highly thiolated α-CD-SH, α-CD-Cya, and α-CD-MSA exhibited with mucus 5.6-, 15.7- and 2.8-fold improved dynamic viscosity, while improvement was 7.7-, 6.1-, and 5.4-fold for the corresponding thiolated ß-CDs and 12.3-, 15.4- and 17.8-fold for the corresponding thiolated γ-CDs compared with native CDs, respectively. A prolonged mucosal residence time following the rank order γ > ß > α was observed for all thiolated CDs, whereby γ-CD-Cya, nonionic highly thiolated ß-CD-SH and α-CD-Cya showed the highest mucoadhesive properties. CONCLUSION: A high degree of thiolation and the introduction of cationic charges are mainly responsible for high mucoadhesive properties of CDs.

Self-Assembly of Cyclodextrin-Coated Nanoparticles:Fabrication of Functional Nanostructures for Sensing and Delivery.

In recent years, the bottom-up approach has emerged as a powerful tool in the fabrication of functional nanomaterials through the self-assembly of nanoscale building blocks. The cues embedded at the molecular level provide a handle to control and direct the assembly of nano-objects to construct higher-order structures. Molecular recognition among the building blocks can assist their precise positioning in a predetermined manner to yield nano- and microstructures that may be difficult to obtain otherwise. A well-orchestrated combination of top-down fabrication and directed self-assembly-based bottom-up approach enables the realization of functional nanomaterial-based devices. Among the various available molecular recognition-based "host-guest" combinations, cyclodextrin-mediated interactions possess an attractive attribute that the interaction is driven in aqueous environments, such as in biological systems. Over the past decade, cyclodextrin-based specific host-guest interactions have been exploited to design and construct structural and functional nanomaterials based on cyclodextrin-coated metal nanoparticles. The focus of this review is to highlight recent advances in the self-assembly of cyclodextrin-coated metal nanoparticles driven by the specific host-guest interaction.

Inclusions of Pesticides by ß-Cyclodextrin in Solution and Solid State: Chlorpropham, Monuron, and Propanil.

Persistence and degradation are important factors in determining the safe use of such synthetic products, and numerous studies have been addressed to develop pesticide remediation methods aimed at ameliorating these features. In this frame, the use of different cyclodextrins (CDs) molecules has attracted considerable attention due to their well-known non-toxic nature, limited environmental impact, and capability to reduce the environmental and health risks of pesticides. CDs appear to be a valuable tool for the elimination of pesticides from polluted areas as well as for better pesticide formulations that positively influence their hydrolysis or degradation. The present work investigates the interaction between ß-cyclodextrins and three commonly used pesticides (i.e., chlorpropham, monuron, and propanil) both in solution and in the solid state by means of UV-Vis, FT-IR, and X-ray powder diffractometry. We show that such interactions result in all three cases in the formation of inclusion complexes with a 1:1 stoichiometry and binding constants (Kb) of 369.9 M-1 for chlorpropham, 292.3 M-1 for monuron, and 298.3 M-1 for propanil. We also report the energy-minimized structures in silico for each complex. Our data expand and complement the available literature data in indicating CDs as a low-cost and very effective tool capable of modulating the properties that determine the environmental fate of pesticides.

Templated Enzymatic Synthesis of δ-Cyclodextrin.

While α-, ß-, and γ-cyclodextrin (CD) are ubiquitous hosts employed by supramolecular chemists, δ-CD (formed from nine α-1,4-linked glucopyranose units) has received very little attention. α-, ß-, and γ-CD are the major products of the enzymatic breakdown of starch by cyclodextrin glucanotransferase (CGTase), but δ-CD forms only transiently in this reaction, as a minor component of a complex mixture of linear and cyclic glucans. In this work, we show how δ-CD can be synthesized in unprecedented yields by employing a bolaamphiphile template in an enzyme-mediated dynamic combinatorial library of cyclodextrins. NMR spectroscopy studies revealed that δ-CD can thread up to three bolaamphiphiles forming [2]-, [3]-, or [4]-pseudorotaxanes, depending on the size of the hydrophilic headgroup and the length of the alkyl chain axle. Threading of the first bolaamphiphile occurs in fast exchange on the NMR chemical shift time scale, while subsequent threading occurs in slow exchange. To extract quantitative information for 1:2 and 1:3 binding events occurring in mixed exchange regimes, we derived equations for nonlinear curve fitting that take into consideration both the chemical shift changes for species in fast exchange and the integrals for species in slow exchange to determine Ka1, Ka2, and Ka3. Template T1 could be used to direct the enzymatic synthesis of δ-CD due to the cooperative formation of a 1:2 complex─the [3]-pseudorotaxane δ-CD·T12. Importantly, T1 is recyclable. It can be readily recovered from the enzymatic reaction by precipitation and reused in subsequent syntheses enabling preparative-scale synthesis of δ-CD.

Cyclodextrin Conjugated α-Bisabolol Suppresses FAK Phosphorylation and Induces Apoptosis in Pancreatic Cancer.

BACKGROUND/AIM: α-Bisabolol is an essential oil component extracted from plants, such as chamomile. We have previously reported that α-bisabolol suppressed proliferation, invasion, and motility of pancreas cancer. Cyclodextrin improved the solubility of α-bisabolol, therefore it enabled to administer intravenously. The aim of this study was to clarify the effect of cyclodextrin conjugated α-bisabolol (CD-BSB) and the signals pathways associated with α-bisabolol for pancreatic cancer. MATERIALS AND METHODS: Human pancreatic cancer cell lines were treated with or without CD-BSB. Cytomorphology and apoptosis were assessed in these treated groups. In addition, several phosphorylated proteins were analyzed to clarify the signal pathway concerning CD-BSB. In subcutaneous xenograft model, tumor volume and Ki-67 expression were evaluated among Control (untreated), CD-BSB, or Gemcitabine (GEM). RESULTS: CD-BSB significantly changed cytomorphology and induced apoptosis in pancreatic cancer cells. CD-BSB suppressed phosphorylation of focal adhesion kinase (FAK). In addition, pFAK 397 was inhibited by CD-BSB in a concentration-dependent manner in cancer cells. In the subcutaneous xenograft models, the tumor volume in the CD-BSB groups was lower than Control groups. Ki67-positive cells in CD-BSB treated group were lower than the GEM-treated groups. CONCLUSION: We clarified the efficiency of CD-BSB in xenograft tumor using intravenous administration. α-Bisabolol suppresses phosphorylation of FAK 397 and impairs cytoskeletal polymerization in a pancreatic cancer cell line. Further investigations are required to reveal the precise mechanisms of the antitumor effects of solubilized α-bisabolol to facilitate its clinical application. Our data indicate that solubilized α-bisabolol has therapeutic potential and could improve the prognosis of cancer patients.

A Review of Applications of Solid-State Nuclear Magnetic Resonance (ssNMR) for the Analysis of Cyclodextrin-Including Systems.

Cyclodextrins, cyclic oligosaccharides composed of five or more α-D-glucopyranoside units linked by α-1,4 glycosidic bonds, are widely used both in their native forms as well as the components of more sophisticated materials. Over the last 30 years, solid-state nuclear magnetic resonance (ssNMR) has been used to characterize cyclodextrins (CDs) and CD-including systems, such as host-guest complexes or even more sophisticated macromolecules. In this review, the examples of such studies have been gathered and discussed. Due to the variety of possible ssNMR experiments, the most common approaches have been presented to provide the overview of the strategies employed to characterize those useful materials.

Cyclodextrin-metal-organic frameworks in molecular delivery, detection, separation, and capture: An updated critical review.

Metal-organic frameworks (MOFs) are coordination compounds with tuneable structures and controllable functions. However, the biological toxicity of traditional MOFs materials is often inevitable, making their application in the biological field have many limitations. Therefore, frontier research increasingly focuses on developing biocompatible MOFs materials. Cyclodextrins (CDs), derived from starch, are favored by various biomaterials due to their good biosafety and are often seen in the preparation and application of MOFs materials. This review describes the features of MOFs materials, and the various preparation methods of CD-MOFs are analyzed in detail from the perspective of CD classification. Additionally, the promising applications of CD-MOFs materials for delivery, detection, separation, and capture of active molecules in recent studies are systematically discussed and summarized. In terms of safety, the CD-MOFs materials are meticulously summarized. Finally, this review presents the challenges and future prospects regarding the current CD-MOFs-based materials, which will shed new light on the application of such materials in various fields.

Nanosponges- Versatile Platform as Drug Carrier.

BACKGROUND: Recently, nano-drug delivery systems have become an integral part of the most novel drug delivery systems and have gained considerable importance owing to various advantages such as carriers for poorly soluble drugs, targeting molecules at the desired site, protection from degradation etc. Objective: One of the most studied areas of nanotechnology is nanosponges. The objective of this review was to extensively summarize the various strategies for the preparation, characterization and applications of nanosponges. METHODS: In the current mini-review, we conducted a systemic search of the literature and patent inventions focusing on nanosponges. The summary of the search was inclusive of various aspects of nanosponges, such as drug characteristics to be considered while incorporating in nanosponges, other crucial additives during formulation of nanosponges, methods of preparation, characterization and applications of nanosponges in pharmaceuticals. RESULTS: Nanosponges are nanocarriers for both lipophilic and hydrophilic drugs. These are prepared by different methods such as emulsion-solvent evaporation, solvent method, melting method, ultrasound assisted method etc., and all these methods were less time consuming, more economical and evaluated by sophisticated techniques available for routine analysis. These are among the most feasible alternative to address several formulation difficulties associated with the physicochemical properties of the drug. The porous nature and small particle size are vital properties of the nanosponges that contribute crucially to correcting the drawbacks of the drug. The properties of the nanosponges can be enhanced when combined with cyclodextrins. Extensive research work has been carried out in past to explore cyclodextrin based nanosponges. Besides, it is also used for smart targeting of tumors and for drug release in a sustainable pattern. Nanosponges can be prepared by simple methods. These can be tuned to release the drug by different routes so as to achieve the maximum benefits of the drug. CONCLUSION: Huge amount of research has been carried out on nanosponges as drug carrier. The method of preparation and characterization of nanosponges are quite economical and routinely available. Owing to potential benefits and probable applications, these can be used as efficient carriers for certain drugs. The authors expect that the current review will guide the investigation of the nanosponges as nanodrug delivery systems.

Cyclodextrin-Based Arsenal for Anti-Cancer Treatments.

Anti-cancer drugs are mostly limited in their use due to poor physicochemical and biopharmaceutical properties. Their lower solubility is the most common hurdle limiting their use upto their potential. In the recent years, the cyclodextrin (CD) complexation have emerged as existing approach to overcome the problem of poor solubility. CD-based nano-technological approaches are safe, stable and showed well in vivo tolerance and greater payload for encapsulation of hydrophobic drugs for the targeted delivery. They are generally chosen due to their ability to get self-assembled to form liposomes, nanoparticles, micelles and nano-sponges etc. This review paper describes a birds-eye view of the various CD-based nano-technological approaches applied for the delivery of anti-cancer moieties to the desired target such as CD based liposomes, niosomes, niosoponges, micelles, nanoparticles, monoclonal antibody, magnetic nanoparticles, small interfering RNA, nanorods, miscellaneous formulation of anti-cancer drugs containing CD. Moreover, the author also summarizes the various shortcomings of such a system and their way ahead.

Evaluation of polyanionic cyclodextrins as high affinity binding scaffolds for fentanyl.

Cyclodextrins (CDs) have been previously shown to display modest equilibrium binding affinities (Ka ~ 100-200 M-1) for the synthetic opioid analgesic fentanyl. In this work, we describe the synthesis of new CDs possessing extended thioalkylcarboxyl or thioalkylhydroxyl moieties and assess their binding affinity towards fentanyl hydrochloride. The optimal CD studied displays a remarkable affinity for the opioid of Ka = 66,500 M-1, the largest value reported for such an inclusion complex to date. One dimensional 1H Nuclear Magnetic Resonance (NMR) as well as Rotational Frame Overhauser Spectroscopy (2D-ROESY) experiments supported by molecular dynamics (MD) simulations suggest an unexpected binding behavior, with fentanyl able to bind the CD interior in one of two distinct orientations. Binding energies derived from the MD simulations work correlate strongly with NMR-derived affinities highlighting its utility as a predictive tool for CD candidate optimization. The performance of these host molecules portends their utility as platforms for medical countermeasures for opioid exposure, as biosensors, and in other forensic science applications.

Voriconazole Eye Drops: Enhanced Solubility and Stability through Ternary Voriconazole/Sulfobutyl Ether ß-Cyclodextrin/Polyvinyl Alcohol Complexes.

Voriconazole (VCZ) is a broad-spectrum antifungal agent used to treat ocular fungal keratitis. However, VCZ has low aqueous solubility and chemical instability in aqueous solutions. This study aimed to develop VCZ eye drop formulations using cyclodextrin (CD) and water-soluble polymers, forming CD complex aggregates to improve the aqueous solubility and chemical stability of VCZ. The VCZ solubility was greatly enhanced using sulfobutyl ether ß-cyclodextrin (SBEßCD). The addition of polyvinyl alcohol (PVA) showed a synergistic effect on VCZ/SBEßCD solubilization and a stabilization effect on the VCZ/SBEßCD complex. The formation of binary VCZ/SBEßCD and ternary VCZ/SBEßCD/PVA complexes was confirmed by spectroscopic techniques and in silico studies. The 0.5% w/v VCZ eye drop formulations were developed consisting of 6% w/v SBEßCD and different types and concentrations of PVA. The VCZ/SBEßCD systems containing high-molecular-weight PVA prepared under freeze-thaw conditions (PVA-H hydrogel) provided high mucoadhesion, sustained release, good ex vivo permeability through the porcine cornea and no sign of irritation. Additionally, PVA-H hydrogel was effective against the filamentous fungi tested. The stability study revealed that our VCZ eye drops provide a shelf-life of more than 2.5 years at room temperature, while a shelf-life of only 3.5 months was observed for the extemporaneous Vfend® eye drops.

Interactions between Sodium Hyaluronate and ß-Cyclodextrin as Seen by Transport Properties.

Knowledge of mass transport parameters, diffusion, and viscosity of hyaluronic acid (HA) in the presence of cyclodextrins is of considerable importance for areas such as food packaging and drug delivery, among others. Despite a number of studies investigating the functionalization of HA or the corresponding sodium salt by cyclodextrins, only a few studies have reported the effect of cyclodextrins on the mass transport of HA in the presence of these oligosaccharides. Here, we report the tracer binary and ternary interdiffusion coefficients of sodium hyaluronate (NaHy) in water and aqueous ß-cyclodextrin solutions. The diffusion behavior of sodium hyaluronate was dependent on the reduced viscosity of NaHy, which, in turn, presented a concave dependence on concentration, with a minimum at approximately 2.5 g dm-3. The significant decrease in the limiting diffusion coefficient of NaHy (at most 45%) at NaHy concentrations below 1 g dm-3 in the presence of ß-cyclodextrin, taking water as the reference, allowed us to conclude that NaHy strongly interacted with the cyclodextrin.

The Role of Cyclodextrins in COVID-19 Therapy-A Literature Review.

Coronavirus disease-19 (COVID-19) emerged in December 2019 and quickly spread, giving rise to a pandemic crisis. Therefore, it triggered tireless efforts to identify the mechanisms of the disease, how to prevent and treat it, and to limit and hamper its global dissemination. Considering the above, the search for prophylactic approaches has led to a revolution in the reglementary pharmaceutical pipeline, with the approval of vaccines against COVID-19 in an unprecedented way. Moreover, a drug repurposing scheme using regulatory-approved antiretroviral agents is also being pursued. However, their physicochemical characteristics or reported adverse events have sometimes limited their use. Hence, nanotechnology has been employed to potentially overcome some of these challenges, particularly cyclodextrins. Cyclodextrins are cyclic oligosaccharides that present hydrophobic cavities suitable for complexing several drugs. This review, besides presenting studies on the inclusion of antiviral drugs in cyclodextrins, aims to summarize some currently available prophylactic and therapeutic schemes against COVID-19, highlighting those that already make use of cyclodextrins for their complexation. In addition, some new therapeutic approaches are underscored, and the potential application of cyclodextrins to increase their promising application against COVID-19 will be addressed. This review describes the instances in which the use of cyclodextrins promotes increased bioavailability, antiviral action, and the solubility of the drugs under analysis. The potential use of cyclodextrins as an active ingredient is also covered. Finally, toxicity and regulatory issues as well as future perspectives regarding the use of cyclodextrins in COVID-19 therapy will be provided.

Immobilization of Enzymes on Cyclodextrin-Anchored Dehiscent Mesoporous TiO2 for Efficient Photoenzymatic Hydroxylation.

A three-in-one heterogeneous catalyst (UPO@dTiO2-CD) was fabricated by grafting cyclodextrins (CDs) on the dehiscent TiO2 (dTiO2) surface and subsequently immobilizing unspecific peroxygenase (rAaeUPO), which exhibited double enhanced electron/mass transfer in photo-enzymatic enantioselective hydroxylation of the C-H bond. The tunable anatase/rutile phase ratio and dehiscent mesoporous architectures of dTiO2 and the electron donor feature and hydrophobic inner cavity of the CDs are independently responsible for accelerating both electron and mass transfer. The coordination of the photocatalytic and enzymatic steps was achieved by structural and compositional regulation. The optimized UPO@dTiO2-CD not only displayed high catalytic efficiency (turnover number and turnover frequency of rAaeUPO up to >65,000 and 91 min-1, respectively) but also exhibited high stability and reusability.