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Cyclodextrin Derivatives (cyclodextrin + derivative)
Selected AbstractsSynthesis of Some Trifluoromethylated Cyclodextrin Derivatives and Analysis of Their Properties as Artificial Glycosidases and OxidasesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2007Jeannette Bjerre Abstract Cyclodextrin derivatives containing trifluoromethyl groups at C6 of the A and D rings were synthesized for the purpose of creating artificial enzymes. The compounds were synthesized by perbenzylation of ,-cyclodextrin followed by selective A,D-debenzylation according to Sinaÿ. Subsequent oxidation to dialdehyde with Dess,Martin periodinane followed by addition of CF3 by using Arduengo carbene and TMSCF3 led to the C6 -bistrifluoromethylated alcohols. These were either deprotected by hydrogenolysis or subjected to another round of oxidation to provide the corresponding ketones that were deprotected. The trifluoromethylated alcohols were found to be weak artificial enzymes catalysing hydrolysis of nitrophenyl glycosides at neutral pH with a kcat/kuncat of up to 56. It is proposed that this catalysis is analogues to the catalysis performed by related cyanohydrins. The trifluoro ketones were likewise weak articial enzymes catalysing oxidation of amines to nitro derivatives or alcohols to ketones with a kcat/kuncat of up to 133. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Determination of flurbiprofen enantiomers in plasma using a single-isomer amino cyclodextrin derivative in nonaqueous capillary electrophoresis,ELECTROPHORESIS, Issue 17 2008Anne Rousseau Abstract A nonaqueous capillary electrophoresis (NACE) assay was developed for the separation and determination of flurbiprofen enantiomers in plasma samples using 6-monodeoxy-6-mono(3-hydroxy)propylamino-,-cyclodextrin as chiral selector. The nonaqueous background electrolyte was made up of 40,mM ammonium acetate in methanol (MeOH), and flufenamic acid was employed as internal standard. Solid-phase extraction was used for sample cleanup prior to the NACE separation. The NACE method reproducibility was optimized by evaluating different capillary washing sequences between runs. After having tested various conditions, trifluoroacetic acid (1,M) in MeOH was finally selected. Concerning the solid-phase extraction procedure, good and reproducible analyte recoveries were obtained using MeOH for protein denaturation and a polymeric phase combining hydrophobic interactions with anion exchange properties (Oasis® MAX) was selected as extraction sorbent. The method selectivity was not only demonstrated toward a blank plasma sample but also toward other non-steroidal anti-inflammatory drugs. The method was then successfully validated with respect to response function, trueness, precision, accuracy, linearity and limit of quantification. [source] Alteration of the intravenous pharmacokinetics of a synthetic ozonide antimalarial in the presence of a modified cyclodextrinJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2006Susan A. Charman Abstract The pharmacokinetic profile and renal clearance of a novel synthetic ozonide antimalarial (1) was found to be significantly altered when intravenously administered to rats as a cyclodextrin-based formulation (0.1 M Captisol®, a sulfobutylether ,-cyclodextrin derivative (SBE7 -,-CD)) compared to a cyclodextrin-free isotonic buffered glucose formulation. There was an 8.5-fold decrease in the steady-state blood volume of distribution, a 6.6-fold decrease in the mean residence time and a greater than 200-fold increase in renal clearance of 1 when administered in the cyclodextrin formulation. Analysis of the whole blood and plasma concentration profiles revealed an essentially constant blood to plasma ratio when 1 was administered in the cyclodextrin-free formulation, whereas this ratio changed as a function of time when administered in the presence of the cyclodextrin derivative. It is postulated that the observed differences were due to a very strong complexation interaction between 1 and the cyclodextrin, resulting in a slow dissociation of the complex in vivo, and altered distribution and excretion profiles. Preliminary studies using isothermal titration calorimetry (ITC) indicated that the association constant for the 1/Captisol® complex was approximately two orders of magnitude higher than reported for typical drug/cyclodextrin complexes. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:256,267, 2006 [source] Cytotoxic evaluation of injectable cyclodextrin nanoparticlesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2006Erem Memisoglu-Bilensoy Nanoparticles were prepared using ,-CDC6, which is an amphiphilic , -cyclodextrin derivative modified on the secondary face with 6C aliphatic esters. A nanoprecipitation technique was used to prepare the blank nanoparticles without any surfactant and nanoparticles containing Pluronic F68 as surfactant in a concentration range of 0.1 to 1%. Nanoparticle formulations were characterized by particle size distribution and zeta potential measurements. Entrapment efficiency and in-vitro release profiles were determined and the cytotoxicity of these injectable nanospheres was evaluated against mouse fibroblast L929 cell line and human polymorphonuclear cells by methlythiazolyltetrazolium assay. As far as particle size and zeta potential are concerned, there is a relationship between surfactant presence and nanoparticle characteristics. However, these effects are not significant. It was also found that surfactant presence has no effect on model drug nimodipine encapsulation but accelerates the in-vitro release of the drug. Cell culture studies on mouse fibroblasts and human polymorphonuclear cells revealed a concentration-dependent cytotoxicity more pronounced in fibroblast cells. This led to the conclusion that the use of surfactants in injectable nanoparticles prepared from amphiphilic ,-cyclodextrins may lead to altered in-vitro properties and impaired safety for the drug delivery system. [source] Chromatographic evaluation and comparison of three ,-cyclodextrin-based stationary phases by capillary liquid chromatography and pressure-assisted capillary electrochromatographyELECTROPHORESIS, Issue 19 2008Bo Lin Abstract Enantiomer separations were performed on three ,-cyclodextrin-based chiral stationary phases (CSP) containing the pernaphthylcarbamoylated ,-cyclodextrin (CSP 1), peracetylated ,-cyclodextrin (CSP 2) and permethylated ,-cyclodextrin (CSP 3) as chiral selectors by capillary liquid chromatography and pressure-assisted capillary electrochromatography in this study. Triethylammonium acetate/MeOH or phosphate buffer/MeOH was used as the mobile phase. The experimental factors affecting chiral separations have been examined for each CSP, including pH of the buffers, methanol content and applied voltage. Under optimal separation conditions, a number of racemic compounds were resolved into their enantiomers on three cyclodextrin-based CSP. A comparative study on the performance of three CSP revealed the presence of carbonyl functional groups as well as aromatic rings in the cyclodextrin derivatives, enhanced the interaction between the analytes and CSP, and thus improved enantioselectivity of the CSP. [source] Enantioselective Recognition of Aliphatic Amino Acids by ,-Cyclodextrin Derivatives Bearing Aromatic Organoselenium Moieties on the Primary or Secondary SideEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 8 2003Yu Liu Abstract Spectrophotometric titrations have been performed in order to determine the stability constants of inclusion complexation of some aliphatic amino acids with four structurally related organoselenium-modified ,-cyclodextrins: mono(6-phenylseleno-6-deoxy)-,-cyclodextrin (1a), mono[6-(p -methoxyphenylseleno)-6-deoxy]-,-cyclodextrin (1b), mono(2-phenylseleno-2-deoxy)-,-cyclodextrin (2a), and mono[2-(p -methoxyphenylseleno)-2-deoxy]-,-cyclodextrin (2b). Conformation analysis by circular dichroism and 2D NMR spectroscopic studies revealed that the aryl-substituted ,-cyclodextrins gave self-inclusion intramolecular complexes in aqueous solution, while the extent of penetration depended both on the positions and on the structures of substituents. Quantitative investigation on the binding ability of the hosts with amino acids showed that they were able to recognize the size and the shape of guests, affording supramolecular complexes with quite small stability constants ranging from 24 to 355 M,1. The molecular recognition abilities are discussed from the viewpoints of induced-fitting mechanisms, geometric complementary, and cooperative binding processes. Furthermore, these ,-cyclodextrin derivatives displayed considerable enantioselectivity towards L/D -amino acid isomers, giving the highest L -enantioselectivity (up to 8.4) for inclusion complexation between leucine and 2a. The binding modes of L/D -leucine with 1b were elucidated from NOESY studies and the chiral recognition phenomena were interpreted accordingly. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Sulfoalkyl ether-alkyl ether cyclodextrin derivatives, their synthesis, NMR characterization, and binding of 6,-methylprednisoloneJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2005Serena Tongiani Abstract The objective of this study is to see if random alkyl ethers of various sulfoalkyl ether cyclodextrins can be synthesized and characterized. The purpose of the alkylation was to test the hypothesis that an increase in the "height" of a cyclodextrins cavity would help in the binding/complexation of larger more structurally complex molecules. The synthesis of new cyclodextrin derivatives comprising a mixture of sulfoalkyl ether and alkyl ether substituents on the same cyclodextrin ring was performed in aqueous alkaline solutions using various sultones and alkylsulfates. The method presented provided an easy and efficient way to modify cyclodextrins avoiding the use of organic solvents and high quantities of alkylating agents and could be carried out in either a two step or "one pot" single step process. Purification was by neutralization followed by ultrafiltration. The derivatives were characterized by 1D, (1H and 13C), and a 2D NMR technique (HMQC, Heteronuclear Multiple Quantum Coherence). The combination of these techniques allowed an analysis of the degree of substitution and the site of substitution on the cyclodextrin (CD) nucleus. For both ,- and ,-CD, sulfoakylation was preferred on the 2,>,3,>,6 hydroxyls while alkylation was preferred 6,>,2,>,3. Due to the simultaneous presence of short alkyl ether chains and negatively charged sulfoalkyl ether chains, these mixed water-soluble cyclodextrin derivatives, especially those of ,-cyclodextrin, should be able to bind more complex drugs. The improved binding capacity of these new modified CDs with the model drug 6,-methylprednisolone is reported. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2380-2392, 2005 [source] Inhibitory effect of sulfobutyl ether ,-cyclodextrin on DY-9760e-induced cellular damage: In vitro and in vivo studiesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 12 2003Yukihiko Nagase Abstract The effects of water-soluble ,-cyclodextrin derivatives (,-CyDs), such as 2-hydroxypropyl-,-cyclodextrin (HP-,-CyD) and sulfobutyl ether ,-cyclodextrin (SBE7-,-CyD) on cytotoxicity of DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H -indazole dihydrochloride 3.5 hydrate) toward human umbilical vein endothelial cells (HUVECs) in vitro and vascular damage of the auricular vein of rabbits by DY-9760e in vivo were investigated. The spectroscopic study revealed that of the four ,-CyDs SBE7-,-CyD forms the most stable inclusion complex in phosphate-buffered saline, probably because of a synergetic effect of hydrophobic and electrostatic interactions. ,-CyDs inhibited DY-9760e-induced cell death toward HUVECs in an order of G2 -,-CyD,<,,-CyD,<,HP-,-CyD,<,SBE7-,-CyD, which was consistent with the order of the magnitude of stability constants. When the DY-9760e solution was infused into the auricular vein of rabbits for 24 h, SBE7-,-CyD suppressed a DY-9760e-induced irritation such as thrombus, desquamation of the endothelium vasculitis, and perivasculitis. The present data indicated that SBE7-,-CyD formed an inclusion complex with DY-9760e in a buffer solution and possessed the protective effect on DY-9760e-induced cytotoxicity toward HUVECs and vascular damage in rabbits. These results suggested potential use of SBE7-,-CyD as a parenteral carrier for DY-9760e. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2466,2474, 2003 [source] Amphiphilic ,-cyclodextrins modified on the primary face: Synthesis, characterization, and evaluation of their potential as novel excipients in the preparation of nanocapsulesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2002Erem Memi Abstract The purpose of this study was to synthesize and characterize amphiphilic ,-cyclodextrins modified on the primary face with substituents of varying chain lengths (C6 and C14) and bond types (ester or amide). We also aimed to evaluate the potentiality of the new amphiphilic ,-cyclodextrins as excipients for the preparation and optimization of nanocapsules without using surface-active agents. Amphiphilic ,-cyclodextrin derivatives were characterized by 1H-nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, mass spectroscopy, differential scanning calorimetry, and elemental analysis. Nanocapsules prepared by nanoprecipitation were characterized by particle size and zeta potential determination and freeze fracture followed by transmission electron microscopy. The appropriate amphiphilic ,-cyclodextrin and its optimum concentration to be used were determined. Formation and characteristics of the nanocapsules were highly dependent on the structural properties of the modified cyclodextrin, its behavior in the oil,water interface and the viscosity and miscibility of the organic solvent with water. Physical stability after 5-month storage was also evaluated. The results indicated that derivatives with 6C aliphatic chains on the primary face proved to be the most efficient among the amphiphilic ,-CDs in this study. They avoid the use of surfactants in parenteral formulations of nanocapsules. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 1214,1224, 2002 [source] Improvement of Subcutaneous Bioavailability of Insulin by Sulphobutyl Ether ,-Cyclodextrin in RatsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2000KEIICHI TOKIHIRO The objective of this study was to examine and compare how hydrophilic ,-cyclodextrin derivatives (,-CyDs) improve the bioavailability of insulin following subcutaneous injection of insulin solution in rats. When insulin solutions in the absence of ,-CyDs were injected into the dorsal subcutaneous tissues of rats, the absolute bioavailability of insulin calculated from plasma immunoreactive insulin (IRI) levels was approximately 50%. When maltosyl-,-cyclodextrin was added to the solutions, there was no change in the plasma IRI levels and hypoglycaemia compared with those of the insulin-alone solution. Dimethyl-,-cyclodextrin decreased the bioavailability of insulin, although it increased the maximal concentration of IRI in plasma and the capillary permeability of the fluorescein isothiocyanatedextran 40, a non-degraded permeation marker. When insulin solutions containing sulphobutyl ether-,-cyclodextrin with a degree of substitution of the sulphobutyl group of 3,9 (SBE4-,-CyD) were injected, the IRI level rapidly increased and maintained higher IRI levels for at least 8h. The bioavailability of the insulin/SBE4-,-CyD system was about twice that of insulin alone and approached 96%. The enhancing effects of SBE4-,-CyD may be in part due to the inhibitory effects of SBE4-,-CyDs on the enzymatic degradation and/or the adsorption of insulin onto the subcutaneous tissue at the injection site, although this does not apparently facilitate capillary permeability. These results suggest that SBE4-,-CyD in aqueous insulin injection for subcutaneous administration is useful for improving the bioavailability and the hence the pharmacological effects of insulin. [source] Urea bonded cyclodextrin derivatives onto silica for chiral HPLCJOURNAL OF SEPARATION SCIENCE, JSS, Issue 12 2006I. Wayan Muderawan Abstract Several structurally well-defined perfunctionalised cyclodextrin chiral stationary phases (CD CSPs) for high performance liquid chromatography have been successfully prepared by immobilisation of perfunctionalised cyclodextrins on silica through urea linkage(s) using the Staudinger reaction. These CSPs show high chiral recognition efficiency and are utilised in the resolution of various types of racemic compounds. This paper reviews the development of sixteen perfunctionalised cyclodextrin-based CSPs, their preparation, and their application to enantioseparation of seventy-seven racemic compounds under a range of separation conditions. [source] Selectivity tuning of cyclodextrin derivatives by specific substitutionJOURNAL OF SEPARATION SCIENCE, JSS, Issue 18 2003Melanie Junge Abstract A new, highly enantioselective cyclodextrin derivative combining the properties of heptakis(6- O - tert -butyldimethylsilyl-2,3-di- O -methyl)-,-cyclodextrin and heptakis(2,3-di- O -acetyl-6- O - tert -butyldimethylsilyl)-,-cyclodextrin was prepared by exchanging a methyl group for an acetyl substituent in a single glucose unit of heptakis(6- O - tert -butyldimethylsilyl-2,3-di- O -methyl)-,-cyclodextrin. A comparative evaluation of the separation capabilities showed that the enantioselectivity of both "parent" cyclodextrin derivatives is transferred to the new chiral stationary phase. [source] Improved Anti-Inflammatory Properties for Naproxen with Cyclodextrin-Grafted Polysaccharides,MACROMOLECULAR BIOSCIENCE, Issue 7 2006Héctor L. Ramírez Abstract Summary: Mannan and carboxymethylcellulose, previously activated by periodate oxidation, were grafted with mono-6-butylenediamino-6-deoxy- , -cyclodextrin derivatives by reductive alkylation in the presence of sodium borohydride. The formation of supramolecular complexes between these polymers and Naproxen was confirmed by fluorescence spectroscopy. The solubility of the drug was 3.8,4.6 fold increased in the presence of the cyclodextrin-grafted polysaccharides. The in vivo anti-inflammatory property of Naproxen was 1.7 times higher after supramolecular association with , -cyclodextrin-branched mannan. [source] Synthesis and Characterization of Chiral [3,22]-IonenesMACROMOLECULAR SYMPOSIA, Issue 1 2005Reinaldo C. Bazito Abstract Summary: Two [3,22]-ionenes with pendent chiral groups, glucopyranosyl-[3,22]-ionene and ,-cyclodextrin-[3,22]-ionene, were synthesized by the reaction between the tosyl derivatives of the carbohydrate (methyl alpha-glucopyranoside or beta-cyclodextrin) and the tertiary [3,22]-polyamine obtained by selective demethylation of [3,22]-ionene. The derivatives were characterized by 1H NMR spectroscopy, presenting degrees of substitution of 30 and 45% for the glucosyl and cyclodextrin derivatives, respectively. It was shown by using pyrene as the fluorescent probe, that both polymers form hydrophobic domains, characteristic of micelle-mimetic polysoaps in aqueous solution. [source] Chiral separation of the ,2 -sympathomimetic fenoterol by HPLC and capillary zone electrophoresis for pharmacokinetic studiesBIOMEDICAL CHROMATOGRAPHY, Issue 10 2010Thomas Ullrich Abstract The development of methods for the separation of the enantiomers of fenoterol by chiral HPLC and capillary zone electrophoresis (CZE) is described. For the HPLC separation precolumn fluorescence derivatization with naphthyl isocyanate was applied. The resulting urea derivatives were resolved on a cellulose tris(3,5-dimethylphenylcarbamate)-coated silica gel column employing a column switching procedure. Detection was carried out fluorimetrically with a detection limit in the low ng/mL range. The method was adapted to the determination of fenoterol enantiomers in rat heart perfusates using liquid,liquid extraction. As an alternative a CE method was used for the direct separation of fenoterol enantiomers comparing different cyclodextrin derivatives as chiral selectors. 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