Beta-cyclodextrin Derivatives Research Articles

Development of a nasal spray based on cyclodextrin/hydrophobically-modified hydroxypropyl-methyl cellulose for the prevention of viral respiratory infections.

The work aims to develop mucoadhesive and thermo-responsive in situ gelling systems, using hydrophobically-modified hydroxypropyl-methyl cellulose (Sangelose, SG) and beta-cyclodextrin (β-CD) derivatives, for preventing viral respiratory infections. Eight SG/CD systems with varying CD concentrations were evaluated for rheological properties, mucoadhesiveness, spreadability and sprayability via nasal devices; cytotoxicity was in vitro investigated on reconstituted nasal epithelia. Additionally, droplet size distribution and spray deposition were assessed for the most promising systems. The addition of β-CD derivatives to SG solution was responsible for a rapid sol-gel transition within a physiological temperature range (29-34 °C). SG/CD systems were characterized by a prevalence of the elastic properties on the viscous ones at 37 °C, functional to the formation of a protective gel barrier on the mucosa. The most promising systems showed sprayability and spreadability suitable for nasal administration, while in vitro tests demonstrated their non-toxicity. All the sprays were characterized by droplets with size >100 μm, functional to avoid droplet exhalation or lung deposition; spray deposition studies confirmed uniform distribution across nasal turbinates, crucial for trapping inhaled particles. In conclusion, a mucoadhesive and thermo-responsive in situ gelling system consisting of SG and β-CD derivatives was successfully developed as promising nasal spray for the prevention of respiratory infections.

A non-toxic inclusion complexation of loxoprofen with hydroxypropyl-β-cyclodextrin for complete solubility and anti-inflammatory efficacy

In recent days, there has been a significant demand for drugs that are easily soluble, non-toxic, safe, and biocompatible for human use. Recently, active pharmaceutical ingredient (API) complexes with cyclodextrins (CDs) and their derivatives have gained considerable attention. In line with this trend, we have developed an inclusion complex material for loxoprofen using hydroxypropyl derivatives of beta-cyclodextrin (Hyd-β-CD). The formation of the complex between loxoprofen (LXP) and Hyd-β-CD has been confirmed through changes in absorbance and fluorescence intensity, indicating a 1:1 stoichiometric ratio. The addition of Hyd-β-CD significantly enhanced the solubility of LXP, reflecting successful complexation. Proton NMR and ROESY analyses show that the phenyl group of LXP resides within the cavity of the Hyd-β-CD. Further validation is provided by DFT orientations and their associated energy parameters. Cell viability studies indicate that the increased solubility of the inclusion complex (IC) improves the bioavailability of the drug, while toxicity tests show that our IC material does not induce toxicity in normal cells. Moreover, the anti-inflammatory efficacy of LXP is markedly enhanced in its IC form. These findings underscore the potential of IC in extending the application of LXP, especially in pharmaceuticals, where the enhanced stability and efficacy of natural active ingredients and anti-inflammatory agents are crucial.

Modification of nanofiltration membranes using beta-cyclodextrin derivatives with different functional groups for enhanced removal of organic micropollutants

Simultaneous enhancement in the removal of organic micropollutants (OMPs) and water permeance is highly desirable for nanofiltration (NF)-based drinking water treatment. This study employed two cyclodextrin derivatives with different functional groups, i.e., (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBECD), as aqueous additives for polyamide (PA) membrane fabrication. Characterization results revealed that HP-β-CD tended to enrich piperazine (PIP) monomers through hydrogen bonding, resulting in a thin but dense PA layer. Conversely, SBECD moderated PIP diffusion through electrostatic forces and steric hindrance, participated more in the interfacial polymerization reaction and yielded an active layer with a coexistence of polyester and polyamide. Both the CD derivative modified membranes exhibited improved surface hydrophilicity, enhanced roughness, and reduced active layer thickness, leading to over 60 % water permeance improvement without the obvious variation of pore size. This enabled the optimal membranes, especially the HP-β-CD incorporated one, highly advantageous in overcoming the trade-off effect between water permeance and OMP rejection. Meanwhile, the strongly negatively charged SBECD modified membrane showed reduced rejections for divalent cations, making it more resistant to scaling. This study offers an efficient approach to tailoring membrane water/solute selectivity and solute/solute selectivity, which has great potential in NF membrane development for drinking water treatment.

Deep eutectic solvents combined with beta-cyclodextrin derivatives for chiral separation of typical adrenergic receptor agonists by capillary electrophoresis with amperometric detection

Enantioseparation has always been one of the research hotspots and difficulties in the field of modern separation science. In this work, a binary chiral electrophoretic separation system was constructed using deep eutectic solvents (DESs) coupled with beta-cyclodextrin derivatives based on capillary electrophoresis with amperometric detection system, and five groups of typical adrenergic receptor agonists (adrenaline, salbutamol, isoproterenol, norepinephrine and terbutaline) were selected as the model enantiomers. The effects of additive types and contents of DESs and cyclodextrins, and the pH value and concentration of the running buffer on the resolution of the selected chiral compounds were investigated in detail. The mechanism of DESs improving separation was explored preliminarily by means of UV spectrophotometry, which was further verified based on the comparison of single and mixed components of choline chlorine-urea DES. Under the optimum conditions, the relative standard deviations for inter-day and intra-day repeatability of the migration time, peak area and resolution for adrenaline and salbutamol were within 8.7%, and the limits of detection reached 0.030 μg mL−1 (S/N = 3). The recovery data were in the range of 96.3–118.7%. The developed methods have been applied for the analyses of (+)-adrenaline hydrochloride injection and (±)-salbutamol aerosol. This binary chiral electrophoretic separation system by CE-AD has high detection sensitivity and low analytical cost, providing an alternative for the separation and analysis of chiral drugs.

Formation and Physico-Chemical Evaluation of Nifedipine-hydroxypropyl-β-cyclodextrin and Nifedipine-methyl-β-cyclodextrin: The Development of Orodispersible Tablets

The novelty in this study is the development of new orodispersible tablets containing nifedipine (NIF) as the active ingredient. Initially, the formation of inclusion complexes between nifedipine and two derivatives of beta-cyclodextrin, namely, hydroxypropyl-β-cyclodextrin (HP-β-CD) and methyl-β-cyclodextrin (Me-β-CD), was established. Inclusion complexes of nifedipine were prepared by different procedures: kneading, coprecipitation and lyophilization methods, using a 1:1 molar ratio among the drug and cyclodextrin compounds. A physical mixture was also developed for comparison, with the same molar ratio. The physicochemical and structural properties of these obtained complexes were subsequently analysed using Fourier-transform infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray diffraction techniques. The lyophilization method of preparation leads to obtaining the complete inclusion of nifedipine in the used cyclodextrin cavity, for both the derivative cyclodextrins. After that, preformulation studies and manufacturing of orodispersible tablets containing NIF-HP-β-CD and NIF-Me-β-CD, respectively, inclusion complexes were advanced. The obtained findings show that only F3 (which contains NIF-HP-β-CD) and F6 (which contains NIF-Me-β-CD) have a suitable flowability for the direct compression materials.

Bisphenol A Adsorption on Silica Particles Modified with Beta-Cyclodextrins.

This study presents the synthesis of silica particles bearing two beta-cyclodextrin (BCD) (beta-cyclodextrin-BCD-OH and diamino butane monosubstituted beta-cyclodextrin-BCD-NH2). The successful synthesis of the BCD-modified silica was confirmed by FT-IR and TGA. Using contact angle measurements, BET analysis and SEM characterization, a possible formation mechanism for the generation of silica particles bearing BCD derivatives on their surface was highlighted. The obtained modified silica displayed the capacity to remove bisphenol A (BPA) from wastewater due to the presence of the BCD moieties on the surface of the silica. The kinetic analysis showed that the adsorption reached equilibrium after 180 min for both materials with qe values of 107 mg BPA/g for SiO2-BCD-OH and 112 mg BPA/g for SiO2-BCD-NH2. The process followed Ho’s pseudo-second-order adsorption model sustaining the presence of adsorption sites with different activities. The fitting of the Freundlich isotherm model on the experimental results was also evaluated, confirming the BCD influence on the materials’ adsorption properties.

Comparing the extraction performance of cyclodextrin-containing supramolecular deep eutectic solvents versus conventional deep eutectic solvents by headspace single drop microextraction

A headspace single drop microextraction (HS-SDME) method coupled with high performance liquid chromatography was developed to compare the extraction of eighteen aromatic organic pollutants from aqueous solutions using cyclodextrin-based supramolecular deep eutectic solvents (SUPRADESs) and alkylammonium halide-based conventional deep eutectic solvents (DESs). Different derivatives of beta-cyclodextrin (β-CD) were employed as hydrogen bond acceptors (HBA) in SUPRADESs and the extraction performance investigated. SUPRADES comprised of the 20 wt% native β-CD HBA provided the highest enrichment factors of analytes compared to SUPRADESs comprised of other derivatives of β-CD (random methylated β-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, and 2-hydroxypropyl β-cyclodextrin). In addition, native β-CD and its derivatives were dissolved in the neat DESs and their effect on the extraction of analytes examined. Dissolution of 20 wt% native β-CD in the choline chloride ([Ch+][Cl−]):2Urea DES resulted in a significant increase in the extraction efficiencies of target analytes compared to the neat [Ch+][Cl−]:2Urea DES. Under optimum conditions, the extraction method required a solvent microdroplet of 6.5 μL, 1000 rpm stir rate, 30% (w/v) salt concentration, and a temperature of 40 °C. The tetrabutylammonium chloride: 2 lactic acid DES resulted in the highest enrichment factors while the [Ch+][Cl−]:2Urea DES had the lowest for most of the analytes among the evaluated solvents. The method provided limits of detection (LODs) down to 35 μg L−1. Furthermore, the developed method was applied for the analysis of spiked tap and lake water, where relative recoveries ranging from 83.7% ̶ 119.7% and relative standard deviations lower than 19.2% were achieved.

Novel Chemical Architectures Based on Beta-Cyclodextrin Derivatives Covalently Attached on Polymer Spheres.

This study presents the synthesis and characterization of polymer derivatives of beta-cyclodextrin (BCD), obtained by chemical grafting onto spherical polymer particles (200 nm) presenting oxirane functional groups at their surface. The polymer spheres were synthesized by emulsion polymerization of styrene (ST) and hydroxyethyl methacrylate (HEMA), followed by the grafting on the surface of glycidyl methacrylate (GMA) by seeded emulsion polymerization. The BCD-polymer derivatives were obtained using two BCD derivatives with hydroxylic (BCD-OH) and amino groups (BCD-NH2). The degree of polymer covalent functionalization using the BCD-OH and BCD-NH2 derivatives were determined to be 4.27 and 19.19 weight %, respectively. The adsorption properties of the materials were evaluated using bisphenol A as a target molecule. The best fit for the adsorption kinetics was Lagergren’s model (both for Qe value and for R2) together with Weber’s intraparticle diffusion model in the case of ST-HEMA-GMA-BCD-NH2. The isothermal adsorption evaluation indicated that both systems follow a Langmuir type behavior and afforded a Qmax value of 148.37 mg g−1 and 37.09 mg g−1 for ST-HEMA-GMA-BCD-NH2 and ST-HEMA-GMA-BCD-OH, respectively. The BCD-modified polymers display a degradation temperature of over 400 °C which can be attributed to the existence of hydrogen bonds and BCD thermal degradation pathway in the presence of the polymers.

Novel chemical architectures based on beta-cyclodextrin derivatives covalently attached on polymer spheres

Novel chemical architectures based on beta-cyclodextrin derivatives covalently attached on polymer spheres

Computational Screening of a Functional Cyclodextrin Derivative for Suppressing a Side Effect of Doxorubicin.

The binding affinity of the beta-cyclodextrin (β-CyD) derivatives with Doxorubicin (Dox) is evaluated by means of the 3D-RISM/KH theory combined with the molecular dynamics simulation in order to screen the compounds for suppressing a side-effect of the cancer drug. A protocol revised for the external and conformational entropies of the host-guest system is employed to calculate the binding free energy. It is found that the direct interactions of CyD with Dox and the desolvation free-energies of the both compounds largely cancel out to leave moderate contributions to the affinity, which are comparable to those from the entropies. The results shed light on the entropy terms for determining the binding affinity, although the external-entropy terms are essentially constant over all the compounds examined and do not affect the screening. The theoretical result is compared with the experimental data of the association constant for a CyD derivative which was predicted to be the best compound by the preliminary calculation without the entropy terms.

Stability, biological and biopharmaceutical evaluation of the inclusion complexes of the antifungal and antiprotozoal drug candidate 2-(2-nitrovinyl) furan (G-0) with beta cyclodextrin derivatives

The purpose of this work was to evaluate the inclusion complexes (ICs) of 2-(2-nitrovinyl) furan (G-0) with hydroxypropyl and sulfobutylether-β-cyclodextrin intended for drug stabilization. The freeze-dried ICs were subjected to an accelerated stability study, monitored by HPLC-DAD and GC-MS methods. Drug sublimation/volatility has been analyzed through Thermogravimetric Analysis and Headspace Gas Chromatography. Drug dissolution profile in Simulated Vaginal Fluid (SVF) and permeation/retention in bovine vaginal mucosa were also evaluated. The influence of ICs on the “in vitro” antifungal activity against Candida spp. was investigated through Broth Microdilution Method and the cytotoxicity on fibroblasts and keratinocytes, through MTT assay protocol. ICs ensured an optimum drug chemical stability under accelerated conditions and significantly decreased the drug sublimation/volatilization compared with free G-0 and physical mixtures. Both complexes allowed a fast drug release in SVF, but G-0 was not quantified in the receptor compartment, although it was recovery from the mucosa, without significant influence on the complex formation. ICs maintained the antifungal activity against Candida albicans but improved the drug activity against a Candida krusei resistant strain (ICs MIC = 12.5 μg mL−1, G-0 MIC = 25 μg mL−1, Amphotericin B MIC = 20 μg mL−1). Cytotoxicity on fibroblast and keratinocytes followed the ranking order: G-0 > FD G-0/HP-β-CD > FD G-0/SBE-β-CD.

Selectivity Encapsulation of Zingiber cassumunar Roxb. oil by Beta-cyclodextrin Derivatives

Abstract Zingiber cassumunar Roxb. (Plai) is a medical plant widely cultivated in Asia and its essential oil has been reported for several biological activities, such as anti-inflammatory, anti-microbial and anti-oxidant effects. In this work, the essential oil was extracted from Plai by steam distillation with 0.32% yield. (E)-1-(3,4-dimethoxyphenyl) butadiene (DMPBD), (E)-1-(3,4-dimethoxyphenyl) but-3-ene-1-ol (compound D) and terpinen-4-ol were reported as the major components. The components of Plai oil were investigated by GC-MS. It was found that sabinene, terpinen-4-ol and DMPBD were detected as the major components for 23, 20 and 30%, respectively. The three types of beta-cyclodextrins (bCDs) i.e. beta-cyclodextrin (bCD), 2-hydroxypropyl-beta-cyclodextrin (HPbCD) and citric acid crosslinked beta-cyclodextrin (pbCD) were used to form the inclusion complexes with Plai oil to increase the aqueous solubility, selectivity and anti-analgesic properties. The ratio of CDs and plai oil was varied. The amount of terpinen-4-ol and DMPBD were detected by GC-MS. The results showed that terpinen-4-ol was fitted to bCD whereas HPbCD showed the highest selectivity of DMPBD. The pbCD presented the lowest selectivity both terpinen-4-ol and DMPBD. As the results, the different types of CDs showed the different selectivity for inclusion complex formation with major component in Plai oil. The separation of terpinen-4-ol and DMPBD can be done by using CD inclusion complexes. The anti-analgesic property of Plai oil and its complexes will be further studied.

Construction and self-assembly of beta-cyclodextrin derivative composite Langmuir films: Host-guest reaction and nanostructures

The design and preparation of functional beta-cyclodextrin-based composite films are of key importance for wide application fields. This study demonstrates a new route to construct composite films by Langmuir-Blodgett (LB) method via cholesterol-modified beta-cyclodextrin derivative (CD-CHOL). The inclusion complex formation of CD-CHOL and azobenzene derivative (N-Azo) at the air/water interface was investigated. It has been found that the interfacial host-guest recognition could easily occur in the in situ formed CD-CHOL/N-Azo composite films and relatively difficult to occur in the ex situ immersed composite films, because there exist host-guest interaction as well as intermolecular hydrogen bonding interaction. The inclusion complex formation was confirmed by changes in the surface pressure-area isotherms, circular dichroism (CD) and UV–vis spectra of the transferred LB films. And the solvent effect of the composite CD-CHOL/N-Azo films was also investigated, indicating that host-guest interaction between N-Azo and CD-CHOL could occur rather in the nonpolar solvent than the polar solvent. The present research work about beta-cyclodextrin-based composite films by LB method may provide new exploration to prepare organized composite films and demonstrate potential applications in many fields.

A molecular dynamics study of conformations of beta-cyclodextrin and its eight derivatives in four different solvents.

Understanding the atomic level interactions and the resulting structural characteristics is required for developing beta-cyclodextrin (βCD) derivatives for pharmaceutical and other applications. The effect of four different solvents on the structures of the native βCD and its hydrophilic (methylated βCD; MEβCD and hydroxypropyl βCD; HPβCD) and hydrophobic derivatives (ethylated βCD; ETβCD) was explored using molecular dynamics (MD) simulations and solvation free energy calculations. The native βCD, 2-MEβCD, 6-MEβCD, 2,6-DMβCD, 2,3,6-TMβCD, 6-HPβCD, 2,6-HPβCD and 2,6-ETβCD in non-polar solvents (cyclohexane; CHX and octane; OCT) were stably formed in a symmetric cyclic cavity shape through their intramolecular hydrogen bonds. In contrast, βCDs in polar solvents (methanol; MeOH and water; WAT) exhibited large structural changes and fluctuations leading to significant deformations of their cavities. Hydrogen bonding with polar solvents was found to be one of the major contributors to this behavior: solvent-βCD hydrogen bonding strongly competes with intramolecular bonding leading to significant changes in the structural stability of βCDs. An exception to this is the hydrophobic 2,6-ETβCD which retained its spherical cavity in all solvents. Based on this, it is proposed that the 2,6-ETβCD can act as a sustained release drug carrier.

“Back to the Future”: A New Look at Hydroxypropyl Beta-Cyclodextrins

Since the discovery about 30 years ago (2-hydroxypropyl) beta-cyclodextrin, a highly soluble derivative of beta-cyclodextrin, has become an approved excipient of drug formulations included both in the United States and European Pharmacopoeias. It is recommended to use as solubilizer and stabilizer for oral and parenteral formulations. Recently, its pharmacological activity has been recognized in various diseases. The increasing applications require a closer look to the structure-activity relationship. As (2-hydroxypropyl) beta-cyclodextrin (HPBCD) is always a mixture of isomers with various degrees and pattern of hydroxypropylation, no wonder that the products of different manufacturers are often different. Several HPBCDs were compared applying a battery of analytical tools including thin layer chromatography, high performance liquid chromatography (HPLC), HPLC–mass spectrometry (MS), and matrix-assisted laser desorption MS. We studied how the average degree of substitution affects the aggregation behavior, the toxicity, and the solubilizing effect on poorly soluble drugs. We found that the products with low average degree of substitution are more prone to aggregation. The samples studied are nontoxic to Caco-2 cells and have low hemolytic activity. The solubility enhancement of poorly soluble drugs decreases or increases with increasing degree of substitution or shows a maximum curve depending on the properties of the guest.

Study of Cyclodextrin/Fluoroquinolone Inclusion Complexes by Capillary Electrophoresis

AbstractIntroduction: In the present work we evaluated the complexation role of cyclodextrins toward fluoroquinolones in an attempt to assess their potential as new formulation additives for more efficient fluoroquinolone delivery and as selectors in capillary electrophoresis.Material and method: Guest-host interactions of two second generation quinolones, ciprofloxacin and norfloxacin with four cyclodextrins, beta-cyclodextrin (β-CD), gamma-cyclodextrin (γ-CD) and two beta-cyclodextrin derivatives, 2-hydroxypropyl beta-cyclodextrin (HP-β-CD) and randomly methylated beta-cyclodextrin (RAMEB), were tested by capillary electrophoresis in borate running buffer. Experimental parameters like buffer concentration, pH, organic modifier, voltage and cyclodextrin concentration have been varied for a better resolution.Results: In capillary zone electrophoresis ciprofloxacin and norfloxacin are migrating together, a difference in their migration times and thus separation occured by the addition of cyclodextrins.Conclusion: Our results suggest formation of inclusion complexes between fluoroquinolones and cyclodextrins. Differences in their affinity to host molecules resulted in separation of the two fluoroquinolones

Changes in the anti-inflammatory activity of soy isoflavonoid genistein versus genistein incorporated in two types of cyclodextrin derivatives

BackgroundThe isoflavonoid genistein represents the major active compound from soybean, the vegetal product from Glycine max (Fabaceae). The aim of this study is to prove that genistein was incorporated in two semisynthetic cyclodextrins, beta-cyclodextrin derivatives: hydroxypropyl-beta-cyclodextrin and randomly-methylated-beta-cyclodextrin as well as to compare the anti-inflammatory activity of genistein with that of genistein incorporated in these two types of semisynthetic cyclodextrins.ResultsThe animal studies were conducted on 8-week old C57BL/6 J female mice. Inflammation was induced in both ears of each mouse by topical application of 10 micrograms 12-O-tetradecanoylphorbol-3-acetate dissolved in 0.1 ml solvent (acetone : dimethylsulfoxide in a molar ratio 9:1). Thirty minutes later treatment was applied. The inflammatory reaction was correlated with increased values in ear thickness. Treatment with genistein and genistein incorporated in the two cyclodextrins led to decreased values for ear thickness. Better anti-inflammatory action was found for the complexes of genistein. Both haematoxylin-eosin analysis and CD45 marker expression are in agreement with these findings.ConclusionsResults allow concluding that genistein is an active anti-inflammatory phytocompound and its complexation with hydrophilic beta-cyclodextrin derivatives leads to a stronger anti-inflammatory activity.

Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine

Peroral administration of tacrine, the first acetylcholinestearse inhibitor licensed for the treatment of Alzheimer’s disease, is associated with low bioavailability, due to an extended first-pass methabolism, short elimination half-life and hepatotoxicity. Nasal drug delivery may reduce the degree of these problems. Tacrine hydrochloride nasal delivery is here investigated by means of albumin nanoparticles carrying beta cyclodextrin and two different beta cyclodextrin derivatives (hydroxypropyl beta cyclodextrin and sulphobutylether beta cyclodextrin). Bovine serum albumin nanoparticles were obtained using a coacervation method, followed by thermal cross-linking, starting from protein solution at alkaline pH. After preparation, nanoparticles were loaded by soaking from solutions of tacrine hydrochloride and lyophilised. Thermal analysis (differential scanning calorimetry and thermogravimetric analysis) supported by Fourier Transform Infrared Spectroscopy were performed in order to confirm protein cross-linking in nanosphere structure and possible drug/carrier interaction occurred after the loading process. Moreover, size, polydispersity, zeta potential and morphology of the nanoparticles were investigated as well as drug loading, mucoadhesion properties and ex-vivo drug permeation ability. Results indicate that all the nanoparticles presented a mean size and a polydispersity lower than 300 nm and 0.33 nm, respectively, were spherical shaped and negatively charged even after drug loading. Moreover, the presence of the different beta cyclodextrins in the polymeric network affected drug loading and could differently modulate nanoparticle mucoadhesiveness and drug permeation behaviour.

Prevention and Treatment ofStaphylococcus aureusPneumonia with a β-Cyclodextrin Derivative

Staphylococcus aureus pneumonia is a common, potentially life-threatening infection caused by this human pathogen. The only therapies available to treat S. aureus pneumonia are antibiotics, a modality that is jeopardized by the organism's remarkable ability to acquire antimicrobial resistance. S. aureus alpha-hemolysin is a pore-forming cytotoxin that is essential for the pathogenesis of pneumonia. Strains lacking this cytotoxin are avirulent in a murine model of pneumonia; likewise, vaccine-based strategies that antagonize the toxin afford protection against lethal disease. Disruption of the function of this toxin therefore provides a potent mechanism to prevent and/or treat S. aureus pneumonia. beta-Cyclodextrin derivatives are small molecules with a sevenfold symmetry that mirrors the heptameric alpha-hemolysin. These compounds block the assembled alpha-hemolysin pore, compromising toxin function. We report that a modified beta-cyclodextrin compound, IB201, prevents alpha-hemolysin-induced lysis of human alveolar epithelial cells. This protective effect does not result from the ability of the beta-cyclodextrin to impair formation of the oligomeric alpha-hemolysin on the cell surface, supporting a role for this molecule in blockade of the lytic pore. An examination of IB201 in murine S. aureus pneumonia demonstrated that administration of this compound prevents and treats disease, protecting against mortality. Consistent with the vital importance of alpha-hemolysin in pneumonia caused by methicillin-sensitive and highly virulent methicillin-resistant S. aureus strains, IB201 protects against lethal challenge with both types of isolates. These observations, coupled with a favorable safety profile of beta-cyclodextrin compounds, provide a novel strategy that may be developed to combat S. aureus pneumonia.

Preparation and enantioseparation characteristics of three chiral stationary phases based on modified β-cyclodextrin for liquid chromatography

In order to study the effect of the nature and the length of the spacer, three mixed 10-undecenoate/phenylcarbamate derivatives of beta-cyclodextrin have been prepared and linked to allylsilica gel by means of a radical reaction. The chiral recognition ability of the resulting materials, when used as liquid chromatography chiral stationary phases (CSPs), was evaluated using heptane and either 2-propanol or chloroform as organic mobile-phase modifiers. A large variety of racemic compounds have been separated successfully on these CSPs (mainly pharmaceuticals and herbicides). Optimization of these separations was discussed in terms of mobile-phase composition and structural patterns of the injected analytes. The efficiencies of the three prepared materials were compared to those of previously described perphenylated-beta-cyclodextrin column and to analogous cellulose derivative-based CSPs.