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Biomolecules Jan 2023The materials used for the preparation of electrospun mats exhibit a large variety. Among them, cyclodextrins (CDs) and their derivatives have received thorough...
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 β-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.
Topics: Cyclodextrins; Scattering, Small Angle; X-Ray Diffraction; Polymers; Solvents
PubMed: 36830572
DOI: 10.3390/biom13020203 -
Molecules (Basel, Switzerland) Feb 2022Amylomaltase is a well-known glucan transferase that can produce large ring cyclodextrins (LR-CDs) or so-called cycloamyloses via cyclization reaction. Amylomaltases... (Review)
Review
Amylomaltase is a well-known glucan transferase that can produce large ring cyclodextrins (LR-CDs) or so-called cycloamyloses via cyclization reaction. Amylomaltases have been found in several microorganisms and their optimum temperatures are generally around 60-70 °C for thermostable amylomaltases and 30-45 °C for the enzymes from mesophilic bacteria and plants. The optimum pHs for mesophilic amylomaltases are around pH 6.0-7.0, while the thermostable amylomaltases are generally active at more acidic conditions. Size of LR-CDs depends on the source of amylomaltases and the reaction conditions including pH, temperature, incubation time, and substrate. For example, in the case of amylomaltase from , LR-CD productions at alkaline pH or at a long incubation time favored products with a low degree of polymerization. In this review, we explore the synthesis of LR-CDs by amylomaltases, structural information of amylomaltases, as well as current applications of LR-CDs and amylomaltases.
Topics: Bacteria; Binding Sites; Cyclodextrins; Fungi; Glycogen Debranching Enzyme System; Models, Molecular; Molecular Structure; Protein Binding; Protein Conformation
PubMed: 35209232
DOI: 10.3390/molecules27041446 -
Molecules (Basel, Switzerland) May 2018Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and... (Review)
Review
Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and improve their physicochemical properties without molecular modifications. The stoichiometry of drug/CD complexes is most frequently 1:1. However, natural CDs have a tendency to self-assemble and form aggregates in aqueous media. CD aggregation can limit their solubility. Through derivative formation, it is possible to enhance their solubility and complexation capacity, but this depends on the type of substituent and degree of substitution. Formation of water-soluble drug/CD complexes can increase drug permeation through biological membranes. To maximize drug permeation the amount of added CD into pharmaceutical preparation has to be optimized. However, solubility of CDs, especially that of natural CDs, is affected by the complex formation. The presence of pharmaceutical excipients, such as water-soluble polymers, preservatives, and surfactants, can influence the solubilizing abilities of CDs, but this depends on the excipients' physicochemical properties. The competitive CD complexation of drugs and excipients has to be considered during formulation studies.
Topics: Chemical Phenomena; Chemistry, Pharmaceutical; Cyclodextrins; Solubility; Solvents
PubMed: 29751694
DOI: 10.3390/molecules23051161 -
International Journal of Molecular... Jan 2022Pseudopolyrotaxanes (PPRs) are supramolecular structures consisting of macrocycles able to thread on a linear polymer chain in a reversible, non-covalent way, often...
Pseudopolyrotaxanes (PPRs) are supramolecular structures consisting of macrocycles able to thread on a linear polymer chain in a reversible, non-covalent way, often referred to in the literature as "molecular necklaces". While the synthesis and reaction mechanisms of these structures in solution have been widely described, their solvent-free production has received little attention, despite the advantages that this route may offer. We propose in this work a kinetic mechanism that describes the PPR formation in the solid phase as a process occurring in two consecutive stages. This mechanism has been used to investigate the spontaneous formation of a PPR that occurs when grinding α-Cyclodextrin (α-CD) with polyethylene glycol (PEG). In the threading stage, the inclusion of the polymer and subsequent release of the water molecules lodged in the cavity of the macrocycle cause vibrational changes that are reflected in the time-dependence of the FTIR-ATR spectra, while the further assembly of PPRs to form crystals produces characteristic reflections in the XRD patterns, due to the channel-like arrangement of CDs, that can be used to track the formation of the adduct in crystalline form. The effects that working variables have on the kinetics of the reaction, such as temperature, feed ratio, molar mass of the polymer and the introduction of an amorphous block in the polymer structure, have been investigated. The rate constants of the threading step increase with the temperature and the activation energy of the process increases at lower proportions of CD to PEG. This is attributed to the lower degree of covering of the polymer chain with CDs that reduces the hydrogen-bonding driven stabilization between adjacent macrocycles. The formation of crystalline PPR, which takes place slowly at room temperature, is markedly promoted at higher temperatures, with lower proportions of CD favoring both the formation and the growth of the crystals. The molar mass of the polymer does not modify the typical channel-like arrangement of packed PPRs but the conversion into crystalline PPR diminishes when using PEG1000 instead of PEG400. At a microscopic level, the crystals arrange into lamellar structures, in the order of hundreds of nm, embedded in an amorphous-like matrix. The introduction of a polypropylene oxide block in the structure of the polymer (Pluronic L62) renders poorer yields and a considerable loss of crystallinity of the product of the reaction. The methodology here proposed can be applied to the general case of inclusion complexes of CDs with drugs in the solid phase, or to multicomponent systems that contain polymers as excipients in pharmaceutical formulations along with CDs.
Topics: Crystallization; Cyclodextrins; Kinetics; Poloxamer; Polyethylene Glycols; Rotaxanes; Solvents; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction; alpha-Cyclodextrins
PubMed: 35054867
DOI: 10.3390/ijms23020685 -
International Journal of Pharmaceutics Oct 2017Cyclodextrin-based nanosponges (CD-NSs) are insoluble, highly cross-linked 3D network polymers used in several scientific and technological fields, the main area of... (Review)
Review
Cyclodextrin-based nanosponges (CD-NSs) are insoluble, highly cross-linked 3D network polymers used in several scientific and technological fields, the main area of investigation concerns the pharmaceutical applications, in which CD-NSs have been mostly employed as drug delivery systems. CD-NSs can be generally grouped into four consecutive generations, taking into account their chemical composition and properties. The 1st generation of NSs are plain nanosponges, subdivided into four main types: urethane, carbonate, ester and ether NSs, depending on the chemical nature of the functional group connecting the CD to the cross-linker. The 2nd generation of NSs are modified nanosponges characterized by specific properties, such as fluorescence and electric charge. The 3rd generation of NSs is represented by stimuli-responsive CD polymers, which are able to modulate their behavior according to external variations in the environment, such as pH and temperature gradients, oxidative/reducing conditions, and finally the 4th generation of NSs, a new family of molecularly imprinted CD polymers (MIPs), exhibiting a high selectivity towards specific molecules. The following review focuses on the evolution of cyclodextrin nanosponges, listing some examples of each generation.
Topics: Cyclodextrins; Drug Delivery Systems; Hydrogen-Ion Concentration; Nanoparticles; Polymers; Temperature
PubMed: 28645630
DOI: 10.1016/j.ijpharm.2017.06.072 -
Molecules (Basel, Switzerland) Aug 2022Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited....
Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, and in silico molecular dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Quantum mechanical calculations showed the formation of hydrogen bonds between QUE with 2HP-β-CD and 2,6Μe-β-CD. Six hydrogen bonds are formed ranging between 2 to 2.8 Å with 2HP-β-CD and four hydrogen bonds within 2.8 Å with 2,6Μe-β-CD. Calculations of absolute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluorescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M) and 2,6Me-β-CD (770 M). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in biological studies.
Topics: Cyclodextrins; Humans; Hydroxyl Radical; Molecular Dynamics Simulation; Quercetin; Solubility; beta-Cyclodextrins
PubMed: 36080258
DOI: 10.3390/molecules27175490 -
Molecules (Basel, Switzerland) Nov 2020Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides consisting of multiple glucose subunits. CDs are widely used in host-guest chemistry and biochemistry... (Review)
Review
Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides consisting of multiple glucose subunits. CDs are widely used in host-guest chemistry and biochemistry due to their structural advantages, biocompatibility, and ability to form inclusion complexes. Recently, CDs have become of high interest in the field of medical imaging as a potential scaffold for the development of a large variety of the contrast agents suitable for magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, positron emission tomography, single photon emission computed tomography, and computed tomography. The aim of this review is to summarize and highlight the achievements in the field of cyclodextrin-based contrast agents for medical imaging.
Topics: Animals; Contrast Media; Cyclodextrins; Diagnostic Imaging; Humans
PubMed: 33261035
DOI: 10.3390/molecules25235576 -
Drugs in R&D Jun 2016According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins,... (Review)
Review
BACKGROUND
According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg.
OBJECTIVES AND METHODS
The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-β-cyclodextrin (HPβCD) and progesterone/HPβCD associations.
RESULTS
The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPβCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPβCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the new formulation of progesterone was shown to be safe and not inferior to other products already on the market, with the exception of progesterone administered vaginally.
CONCLUSIONS
As shown by the results of clinical studies presented in this review, the newly approved medicines containing cyclodextrins have been found to be as effective and as well-tolerated as other medicinal products that do not contain cyclodextrins. Moreover, the newly approved lower dose of diclofenac associated with cyclodextrins is consistent with the European Medicines Agency recommendations reported in the revision of the Assessment Report for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Cardiovascular Risk. Finally, the use of cyclodextrins led to significant increases in solubility and bioavailability of drugs, such as diclofenac and progesterone, and improvement in the efficacy and safety of these drugs.
Topics: 2-Hydroxypropyl-beta-cyclodextrin; Biological Availability; Cyclodextrins; Diclofenac; Drug Compounding; Drug Therapy, Combination; Female; Humans; Male; Pain; Permeability; Pregnancy; Progesterone; Solubility; Treatment Outcome; beta-Cyclodextrins
PubMed: 26939533
DOI: 10.1007/s40268-016-0123-2 -
Biomedicine & Pharmacotherapy =... May 2022Bioactive phytochemicals from natural source have gained tremendous interest over several decades due to their wide and diverse therapeutic activities playing key role... (Review)
Review
Bioactive phytochemicals from natural source have gained tremendous interest over several decades due to their wide and diverse therapeutic activities playing key role as functional food supplements, pharmaceutical and nutraceutical products. Nevertheless, their application as therapeutically active moieties and formulation into novel drug delivery systems are hindered due to major drawbacks such as poor solubility, bioavailability and dissolution rate and instability contributing to reduction in bioactivity. These drawbacks can be effectively overcome by their complexation with different cyclodextrins. Present article discusses complexation of phytochemicals varying from flavonoids, phenolics, triterpenes, and tropolone with different natural and synthetic cyclodextrins. Moreover, the article summarizes complexation methods, complexation efficiency, stability, stability constants and enhancement in rate and extent of dissolution, bioavailability, solubility, in vivo and in vitro activities of reported complexed phytochemicals. Additionally, the article presents update of published patent details comprising of complexed phytochemicals of therapeutic significance. Thus, phytochemical cyclodextrin complexes have tremendous potential for transformation into drug delivery systems as substantiated by significant outcome of research findings.
Topics: Biological Availability; Cyclodextrins; Pharmaceutical Preparations; Phytochemicals; Solubility
PubMed: 35339826
DOI: 10.1016/j.biopha.2022.112862 -
Molecules (Basel, Switzerland) Feb 2021Cyclodextrins (CDs) are a series of cyclic oligosaccharides formed by amylose under the action of CD glucosyltransferase that is produced by Bacillus. After being... (Review)
Review
Cyclodextrins (CDs) are a series of cyclic oligosaccharides formed by amylose under the action of CD glucosyltransferase that is produced by Bacillus. After being modified by polymerization, substitution and grafting, high molecular weight cyclodextrin polymers (pCDs) containing multiple CD units can be obtained. pCDs retain the internal hydrophobic-external hydrophilic cavity structure characteristic of CDs, while also possessing the stability of polymer. They are a class of functional polymer materials with strong development potential and have been applied in many fields. This review introduces the research progress of pCDs, including the synthesis of pCDs and their applications in analytical separation science, materials science, and biomedicine.
Topics: Biomedical Technology; Cellulose; Cyclodextrins; Drug Delivery Systems; Materials Science; Models, Molecular; Research
PubMed: 33669556
DOI: 10.3390/molecules26041090