Cyclodextrin Inclusion Compounds Research Articles

Comparative physicochemical investigation of the inclusion compounds of cyclodextrins with arginine and histidine stereoisomers

The inclusion complexes of α-, β-cyclodextrin and 2-hydroxypropyl-α-cyclodextrin with two amino acid stereoisomers (L-, D-arginine and L-, D-histidine) were studied by using differential scanning calorimetry, thermogravimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy methods. The solid inclusion compounds were prepared in a 1:1 molar ratio of the host and guest using the co-precipitation method. The pH measurements and structural visualization of complexes were carried out. The obtained results proved the formation of the complexes and revealed that the size and the symmetry of the cyclodextrin (CD) and also the structure and flexibility of the amino acid molecule had a significant influence on the complexation interaction. The correlation of the experimental data shows that βCD has a preference to form more stable complexes with levogir isomers of amino acid than αCD and 2-hydroxypropyl-α-cyclodextrin. The complexation of the amino acids isomers was accomplished by partial inclusion of the guest molecule in the CD cavity, and it was observed that CDs could better discriminate between histidine isomers than between arginine isomers.

Determination of Melting Parameters of Cyclodextrins Using Fast Scanning Calorimetry.

The first evidence of native cyclodextrins fusion was registered using fast scanning calorimetry (FSC) with heating rates up to 40,000 K s-1. The endothermal effects, detected at low heating rates, correspond to the decomposition processes. Upon the increase of the heating rate the onset of these effects shifts to higher temperatures, reaching a limiting value at high heating rates. The limiting temperatures were identified as the melting points of α-, β- and γ-cyclodextrins, as the decomposition processes are suppressed at high heating rates. For γ-cyclodextrin the fusion enthalpy was measured. The activation energies of thermal decomposition of cyclodextrins were determined by dependence of the observed thermal effects on heating rates from 4 K min-1 in conventional differential scanning calorimetry to 40,000 K s-1 in FSC. The lower thermal stability and activation energy of decomposition of β-cyclodextrin than for the other two cyclodextrins were found, which may be explained by preliminary phase transition and chemical reaction without mass loss. The obtained values of fusion parameters of cyclodextrins are needed in theoretical models widely used for prediction of solubility and solution rates and in preparation of cyclodextrin inclusion compounds involving heating.

Efficient Persistent Luminescence Tuning Using a Cyclodextrin Inclusion Complex as Efficient Light Conversion Materials

Developing an appropriate method to broaden the color of long persistent luminescence materials has important scientific significance and practical value but remains a great challenge. Herein, we have developed a unique strategy to fine-tune the persistent luminescence using the inclusion complex of rhodamine 6G with (2-hydroxypropyl)-β-cyclodextrin as efficient light conversion materials. The emitting color of the novel persistent luminescence material could be tuned from green to orange by changing the concentration of the light conversion agent. Furthermore, afterglow decay measurements showed that the initial afterglow brightness is 9.65 cd/m2, and the initial afterglow brightness gradually decreased as the cyclodextrin inclusion compound coating increased. This design concept introduces a new perspective for broadening the luminescence color of afterglow phosphors, which may open up new opportunities for persistent luminescence materials toward many emerging applications.

Preparation of gallic acid-hydroxypropyl-β-cyclodextrin inclusion compound and study on its effect mechanism on Escherichia coli in vitro

The purpose of this paper is to optimize the preparation process of gallic acid-hydroxypropyl-β-cyclodextrin inclusion compound and to study its antibacterial effect in vitro. Orthogonal test was used to screen the preparation method of the compound. The microscopic appearance of the compound was observed by microscope, and the solubility of the compound was detected by the dissolution method. The antibacterial activity of the compound was measured by the Oxford cup method. Under the transmission electron microscope, the microstructure of the cells and the intracellular ultrastructure changes were observed. The results showed that when the molar ratio of gallic acid and hydroxypropyl-β-cyclodextrin inclusion was 1:1, the ethanol concentration was 80%, the inclusion temperature was 30 °C, and the inclusion time was 0.5 h, the inclusion effect was the best with an inclusion rate of 99.45%; the solubility of gallic acid before the inclusion was (6.515 ±0.55) mg/mL, while after the inclusion, the solubility increased by more than 100 times to (710.048 ±1.08) mg/mL; gallic acid-hydroxypropyl-β-cyclodextrin inclusion compound could dissolve and destroy the cell membrane of Escherichia coli. The preparation process of gallic acid-hydroxypropyl-β-cyclodextrin inclusion compound was stable and feasible, and there was a good inclusion effect. After the inclusion, the solubility of gallic acid increased significantly; the prepared inclusion compound could inhibit the gram-negative bacteria Escherichia coli by destroying the integrity of the bacterial cell membrane, which could provide data support for the application and development of gallic acid.

In vivo antinociceptive and anti-inflammatory potential of hesperidin and its cyclodextrin inclusion compounds

Introduction. This study aims to evaluate the antinociceptive activity on inflammatory and non-inflammatory nociception models, as well as the anti-inflammatory action of hesperidin and its inclusion compounds with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin. Material and method. For these experiments, we employed nociception models using thermal, chemical and pressure stimuli and an inflammation model for the evaluation of inflammatory edema by plethysmometer test. Results and discussions. The obtained results demonstrate that the HES-βCD inclusion compounds exhibited antinociceptive action predominantly on experimental non-inflammatory nociception models, while HES-HP-βCD exhibited anti-inflammatory and antinociceptive activities predominantly in inflammatory nociception models. Conclusions. This research may be the starting point for future studies regarding the improvement of biopharmaceutical qualities of HES by encapsulation in cyclodextrins. Keywords: hesperidin, cyclodextrin inclusion compunds, antinociceptive, anti-inflammatory activity,

Inclusion of Hydroxycinnamic Acids in Methylated Cyclodextrins: Host-Guest Interactions and Effects on Guest Thermal Stability

There is ongoing interest in exploiting the antioxidant activity and other medicinal properties of natural monophenolic/polyphenolic compounds, but their generally low aqueous solubility limits their applications. Numerous studies have been undertaken to solubilize such compounds via supramolecular derivatization with co-crystal formation with biocompatible coformer molecules and cyclodextrin (CD) complexation being two successful approaches. In this study, eight new crystalline products obtained by complexation between methylated cyclodextrins and the bioactive phenolic acids (ferulic, hydroferulic, caffeic, and p-coumaric acids) were investigated using thermal analysis (hot stage microscopy, thermogravimetry, differential scanning calorimetry) and X-ray diffraction. All of the complexes crystallized as ternary systems containing the host CD, a phenolic acid guest, and water. On heating each complex, the primary thermal events were dehydration and liberation of the respective phenolic acid component, the mass loss for the latter step enabling determination of the host-guest stoichiometry. Systematic examination of the X-ray crystal structures of the eight complexes enabled their classification according to the extent of inclusion of each guest molecule within the cavity of its respective CD molecule. This revealed three CD inclusion compounds with full guest encapsulation, three with partial guest inclusion, and two that belong to the rare class of ‘non-inclusion’ compounds.

Sugammadex

There are a large number of publications which describe the use of cyclodextrins (CDs) in numerous fields, including biomedicine, cosmetics, food industry, wastewater remediation and catalysis. These drugs contain a number of glucose monomers in a ring, creating a cone shape: α (alpha), β (beta), and γ (gamma) cyclodextrins with 6, 7 and 8 glucose subunits respectively. With a hydrophobic interior and hydrophilic exterior, they can form complexes with hydrophobic compounds often conferring solubility and stability to other drugs. The inclusion compounds of cyclodextrins with hydrophobic molecules are able to penetrate body tissues; these can be used to release biologically active compounds under specific conditions. Sugammadex is a unique, selective relaxant binding agent (SRBA) which reverses aminosteroid-induced neuromuscular blockade. It is an alternative to anticholinesterases in anaesthesia and allows use and reversal of rocuronium as a substitute for suxamethonium for rapid sequence induction (RSI).

Novel Trends in Drug Delivery and Application of Curcumin in Dentistry

The frequent use and misuse of the currently used therapeutic agents have led to the evolution of resistantstrains of common pathogens as well as increased incidence of adverse effects associated with their usage.Hence, the search for phytochemicals isolated from plants is considered as a good alternative source. Theminimum number of plant species worldwide has been phytochemically investigated until date, there isa great potential for discovering novel bioactive compounds and drugs. The design and development ofherbal nanoparticles have become frontier research in the nanoformulation arena. Curcumin, a hydrophobicpolyphenol (diferuloylmethane) is a potent Phyto molecule obtained from turmeric (Curcuma longa, FamilyZingiberaceae) has a wide range of biological activities in chronic diseases and a large number of in-vitroand invivo studies in both humans and animals reported that curcumin has provoked properties like antiinflammatory, antioxidant, antimicrobial, antiseptic, antimutagenic, hepatoprotective and immunostimulant.Due to these properties, it is quite useful in dentistry. It has a role in the treatment of periodontal diseasesand oral cancers. But the clinical application of curcumin was limited due to its poor oral bioavailability,which may result from its poor water solubility, its poor pharmacokinetic profile, rapid metabolism, andrapid elimination which ultimately results in poor bioavailability upon oral administration. Therefore theintroduction of novel drug delivery technologies gained the importance to achieve modified delivery ofherbal drugs by increasing the therapeutic value and provides a solution towards increased bioavailabilityof curcumin. However, there is a scarcity of research and information in this field and much work is neededto further investigate the pharmacokinetics, enhance the delivery at the target tissue, the bioavailability, andthe medicinal value of curcumin. In this review, various nanoparticles, micellar formulations, cyclodextrininclusion compounds, and liposomes have been reported in order to improve the bioavailability, solubility,and efficacy of curcumin.

Delivery of pharmaceuticals and other active ingredients with their crystalline cyclodextrin inclusion compounds

In honor of Prof. Thorsteinn Loftsson's 70th birthday, we offer this personal review of our work using cyclodextrins (CDs) complexed with a variety of active ingredients, including pharmaceuticals, for the purpose of improving their delivery to polymer materials, e.g., fibers, films, hydrogels, etc. Using the affinity of CDs to host and form non-covalent inclusion complexes (ICs) with guest molecules, including a variety of high molecular weight polymers, it is possible to readily deliver these guest molecules into polymer materials via either melt or solution processing of their crystalline or soluble guest molecule-CD-ICs or -rotaxanes. This provides the following advantages: i. CDs are non-toxic, implantable, and biodegradable and have earned the GRAS rating from the FDA. ii. Guest molecules, even those that are neat liquids, can form solid crystalline CD-ICs that are thermally stable to~200°C and above. This approach permits facile melt-processing into polymer materials for delivery without migration, loss, or degradation of the active guest ingredient. iii. For guests harmful and toxic to their users and the environment, delivery in the form of crystalline CD-ICs can limit any contact with and release of the included toxic guests before they function and are used. iv. It has been demonstrated that, by simple precipitation methods, neat as-received CDs that adopt cage crystal structures can be readily transformed to their columnar crystal structures containing only water in their channels, which can be easily displaced by small molecule, as well as polymer guests. v. Guest-CD-rotaxanes are water soluble, they protect the threaded guest from sources of degradation, and the CD hydroxyl groups may be modified to direct the guest-CD-rotaxane to specific substrates. For these reasons, here we summarize our contributions to the study of CD inclusion and delivery of a variety of guest molecules, including antibacterials, spermicides, insecticides, flame retardants, and dyes, that can more usefully functionalize polymer materials.

Advance on the nano delivery system of curcumin

Curcumin has various physiological functions such as anti-oxidation, anti-cancer and prevention of Alzheimer's disease, but its poor water solubility and unstable physicochemical property limits the development and application of curcumin. The nano delivery carriers for curcumin prepared by nanotechnology can effectively solve these problems above. This paper summarized the research reports and literatures at home and abroad in recent years, categorized the nanocarriers of curcumin and analysed the definitions, preparation methods, properties and features, advantages and disadvantages of nano-emulsion, solid lipid particles, liposome, cyclodextrin inclusion compound respectively. In addition, this paper predicted application prospects of curcumin in the fields of food and medicine and provided references for the comprehensive development and utilization of curcumin.

Chitosan-based hydrogels loading with thyme oil cyclodextrin inclusion compounds: From preparation to characterization

Hydrogels, based on polysaccharides such as chitosan have found various applications as drug delivery carriers. Three different preparations of pH sensitive chitosan/polyvinyl alcohol hydrogels containing inclusion compounds of thyme oil with methyl-β-, hydroxypropyl-β- and γ-cyclodextrin were developed by using a controlled, bio-compatible and low cost method based on freeze-thaw cycling. The structures and morphology of the hydrogels were characterized by FTIR, optical and scanning electron microscopy. Stable hydrogels of chitosan and polyvinyl alcohol had good mechanical properties and swelling ratios. The water vapor transmission rates of the hydrogels were all in the range of an ideal wound dressing. Encapsulation and release of thyme oil-cyclodextrin inclusion compounds (TM-CD-ICs) in the hydrogels were detected and followed by UV spectroscopy and different mathematical models were applied for evaluating the drug release mechanisms. Hydrogels loaded with TM-CD-ICs had slower and more controlled drug release. The antibacterial activity of the samples was studied by counting the number of surviving both gram-negative and gram-positive bacteria in a broth medium and the results showed antibacterial activity of all prepared hydrogels, especially those containing TM-γCD-ICs. The MTT assay indicated more cell viability of TM-γCD-ICs hydrogels in comparison with those containing β-cyclodextrin inclusion compounds (TM-βCD-ICs hydrogels). Cell attachment study showed great biocompatibility of TM-γCD-ICs hydrogels. Finally, the modified hydrogels can be used in different biomedical applications, such as wound dressings for improving the wound healing process and in drug delivery systems.

Preparation and characterization of chitosan based hydrogels containing cyclodextrin inclusion compounds or nanoemulsions of thyme oil

AbstractHydrogels derived from natural polysaccharides are ideal scaffolds for use in biomedical applications. pH‐sensitive polyvinyl alcohol and chitosan hydrogels containing inclusion compounds of thyme oil (TM) with host methyl‐β‐cyclodextrin (MβCD) and hydroxypropyl‐β‐cyclodextrin (HβCD) and TM nanoemulsion (TM‐nano) were prepared via controlled, biocompatible and low cost freeze–thaw method. The structure of the hydrogels was characterized by Fourier transform IR spectroscopy and optical and scanning electron microscopy. The physicochemical properties of the hydrogels such as gel fraction, swelling ratio and tensile properties were measured. The water vapor transmission rate of the hydrogels indicated that they can maintain a moist environment over the wound bed. Encapsulation and release of antibacterial TM from the hydrogels were determined by UV spectroscopy. In all cases, hydrogels with lower amounts of TM evidenced slower and more controlled release. Different kinetic models were applied for evaluating the drug release mechanism. The antibacterial activity of the samples was studied by counting the number of both Gram‐negative and Gram‐positive bacteria surviving in a broth medium and the results proved the antibacterial activity of all prepared hydrogels. The results of an MTT (3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazolium bromide) assay indicated more cell viability of TM‐nano hydrogels in comparison with those of TM‐βCD inclusion compounds. Cell attachment observations also showed great biocompatibility of TM‐nano hydrogels. The prepared hydrogels, especially those containing TM‐nano, might be used as potential wound dressings to improve the wound healing process. © 2019 Society of Chemical Industry

Associating Polymer Networks Based on Cyclodextrin Inclusion Compounds for Heavy Oil Recovery

This work evaluates an approach to improve the enhanced heavy oil recovery performance of hydrophobic associating polymer. A polymeric system based on water-soluble hydrophobic associating polymer (WSHAP) and cyclodextrin (CD) polymer was proposed in this work. Addition of CD polymer to WSHAP forms interpolymer bridges by inclusion of CD groups with hydrophobic tails, and thereby the network structure is strengthened. The proposed system offers good viscoelasticity, pronounced shear thinning, and interesting viscosity-temperature relations. Sand pack tests indicated that the proposed system can build high resistance factor during the propagation in porous media, and its moderate adsorption phenomenon was represented by the thickness of the adsorbed layer. The relationship between effective viscosity and oil recovery increment indicated that the proposed system can significantly reduce the residual oil saturation due to the “piston-like” propagation. The overall oil recovery was raised by 5.7 and 24.5% of the original oil in place compared with WSHAP and partially hydrolyzed polyacrylamide (HPAM), respectively.

Host–guest intermolecular hydrogen bonds and stability in aqueous media: the benzaldehyde/β-CD case study

The formation of a host–guest system is driven by several contributions. The solvent plays a fundamental role. Usually, in theoretical investigations concerning cyclodextrin inclusion compounds hydrogen bonds between host and guest are studied. Our calculations for the β-cyclodextrin/benzaldehyde semicarbazone system show that hydrogen bonds between host and guest may not determine the preferable guest orientation. In addition, gas and aqueous phase theoretical trends can be distinct in studies concerning CD-based inclusion compounds.

Evidence of the Disassembly of α-Cyclodextrin-octylamine Inclusion Compounds Conjugated to Gold Nanoparticles via Thermal and Photothermal Effects.

Cyclodextrin (CD) molecules form inclusion compounds (ICs), generating dimers that are capable of encapsulating molecules derived from long-chain hydrocarbons. The aim of this study is to evaluate the structural changes experienced by ICs in solution with increasing temperatures. For this, a nuclear magnetic resonance (1H-NMR) titration was performed to determinate the stoichiometric α-cyclodextrin (α-CD):octylamine (OA) 2:1 and binding constant (k = 2.16 M−2) of ICs. Solution samples of α-CD-OA ICs conjugated with gold nanoparticles (AuNPs) were prepared, and 1H-NMR spectra at different temperatures were recorded. Comparatively, 1H-NMR spectra of the sample irradiated with a laser with tunable wavelengths, with plasmons of conjugated AuNPs, were recorded. In this work, we present evidence of the disassembly of ICs conjugated with AuNPs. Thermal studies demonstrated that, at 114 °C, there are reversible rearrangements of the host and guests in the ICs in a solid state. Migration movements of the guest molecules from the CD cavity were monitored via temperature-dependent 1H-NMR, and were verified comparing the chemical shifts of octylamine dissolved in deuterated dimethylsulfoxide (DMSO-d6) with the OA molecule included in α-CD dissolved in the same solvent. It was observed that, at 117 °C, OA exited the α-CD cavity. CD IC dimer disassembly was also observed when the sample was irradiated with green laser light.

Investigation of Cyclodextrin Inclusion Compounds Using FT-IR, SEM and X-Ray Diffraction

Investigation of Cyclodextrin Inclusion Compounds Using FT-IR, SEM and X-Ray Diffraction

In Situ Visualization of the Local Photothermal Effect Produced on α-Cyclodextrin Inclusion Compound Associated with Gold Nanoparticles.

Evidence of guest migration in α-cyclodextrin-octylamine (α-CD-OA) inclusion compound (IC) generated via plasmonic heating of gold nanoparticles (AuNPs) has been studied. In this report, we demonstrate local effects generated by laser-mediated irradiation of a sample of AuNPs covered with inclusion compounds on surface-derivatized glass under liquid conditions by atomic force microscopy (AFM). Functionalized AuNPs on the glass and covered by the ICs were monitored by recording images by AFM during 5 h of irradiation, and images showed that after irradiation, a drastic decrease in the height of the AuNPs occurred. The absorption spectrum of the irradiated sample showed a hypsochromic shift from 542 to 536 nm, evidence suggesting that much of the population of nanoparticles lost all of the parts of the overlay of ICs due to the plasmonic heat generated by the irradiation. Mass spectrometry matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) performed on a sample containing a collection of drops obtained from the surface of the functionalized glass provided evidence that the irradiation lead to disintegration of the ICs and therefore exit of the octylamine molecule (the guest) from the cyclodextrin cavity (the matrix).Graphical Atomic Force Microscopy observation of the disintegration of a cyclodextrin inclusion compound by gold nanoparticles photothermal effectElectronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1322-z) contains supplementary material, which is available to authorized users.

Cyclodextrin inclusion compound crystals for growth of Cu–Au core–shell nanoparticles

The preparation and structural elucidation of the 2α-cyclodextrin/decylamine inclusion compound (IC) by proton nuclear magnetic resonance, rotating frame overhauser effect spectroscopy and powder X-ray diffraction have been achieved. The IC microcrystals were used as a support for the preparation of Au–Cu core–shell nanoparticles by the sputtering method. The coating of copper nanoparticles with gold was verified through anodic stripping voltammetry. The presence of metallic copper and the absence of copper oxides were determined by X-ray photoelectron spectroscopy. These results show that the formation of core–shell Cu–Au by sputtering is an effective approach to prevent the oxidation of Cu particles, leading to potential applications in nanoelectronics.

Studies on polymorph conversion in a new cyclodextrin inclusion compound

4-Phenylpyridine-N-oxide and βCD form a stoichiometric inclusion complex with two polymorphs occurring at different crystallisation times. The irreversible conversion of one polymorph into the other was monitored in real time for the first time.

Improving ITC studies of cyclodextrin inclusion compounds by global analysis of conventional and non-conventional experiments.

The study of 1:1 cyclodextrin inclusion compounds by isothermal titration calorimetry was explored in a theoretical and experimental point of view to compare the efficiency of conventional and non-conventional experiments. All direct and competitive protocols were described and evaluated in terms of accuracy on both binding constant and inclusion enthalpy. Significant improvement in the calorimetric characterization may be obtained by means of the global analysis of non-conventional experiments coupled to the standard titration protocol. While the titration-release approach proved to be the most accurate strategy for classical complexations, the valuable contribution of other non-conventional experiments was demonstrated for issues concerning weak stability, enthalpy, or solubility.