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Sample records for beta cyclodextrin inclusion

  1. Investigation of the beta-cyclodextrin-hydrocortisone inclusion compound.

    PubMed

    Frank, S G; Kavaliunas, D R

    1983-10-01

    The formation of an inclusion compound by beta-cyclodextrin with hydrocortisone has been studied by proton magnetic resonance (1H-NMR) and phase solubility analysis. The magnitude of the chemical shifts of the interior and exterior beta-cyclodextrin protons in the presence of hydrocortisone indicated that hydrocortisone is included within the beta-cyclodextrin cavity and probably interacts with protons on the edge of the torus. The overall stoichiometry of the inclusion compound was not a single, simple relationship, but was unusual in that it was variable and apparently dependent on the relative amounts of hydrocortisone and beta-cyclodextrin in the system. PMID:6644576

  2. Studies on coumestrol/beta-cyclodextrin association: Inclusion complex characterization.

    PubMed

    Franco, Camila; Schwingel, Liege; Lula, Ivana; Sinisterra, Rubén D; Koester, Letícia Scherer; Bassani, Valquiria Linck

    2009-03-18

    Coumestrol is an estrogenic and antioxidant agent, characterized by its low solubility in aqueous and lipophilic media, once in the aglicone form. In order to improve its solubility in water, coumestrol was associated with beta-cyclodextrin in aqueous media followed by freeze-drying and characterized by SEM, (1)H NMR and molecular modeling. The analysis proved the existence of an inclusion complex, with higher probability of inclusion of the coumestrol B-ring into the wider rim of the beta-cyclodextrin molecule. PMID:19028558

  3. Study of Benzyl Salicylate/beta-Cyclodextrin Inclusion Complex Formation by Positron Annihilation

    NASA Astrophysics Data System (ADS)

    Bellitto, V. J.; Hsu Hadley, F. H., Jr.; Trinh, T.

    1996-11-01

    Results of positron annihilation lifetime spectra of beta-cyclodextrin and beta-cyclodextrin complexed with benzyl salicylate,benzyl acetate, or ethyl salicylate in air and vacuum were used to determine the fraction of beta-cyclodextrin which remains uncomplexed in the benzyl salicylate/beta-cyclodextrin 1:2 molar ratio inclusion complex. The intensity of the longest-lived component in vacuum was shown to decrease when the beta-cyclodextrin cavity was filled with benzyl salicylate, benzyl acetate, or ethyl salicylate guest molecules. Comparison of the intensity for beta-cyclodextrin, benzyl salicylate/beta-cyclodextrin 1:2 molar ratio, and 1:1 molar ratio indicated that the benzyl and salicylate moieties each formed an inclusion complex with a molecule of beta-cyclodextrin in the benzyl salicylate/beta-cyclodextrin 1:2 complex. It was determined that the benzyl moiety of the benzyl salicylate molecule is preferred by the beta-cyclodextrin "host" and that only 34of the salicylate moieties are complexed in the benzyl salicylate/beta-cyclodextrin 1:2 sample.

  4. Crystal structure of beta-cyclodextrin-benzoic acid inclusion complex.

    PubMed

    Aree, Thammarat; Chaichit, Narongsak

    2003-02-14

    The inclusion complex of beta-cyclodextrin (beta-CD) with benzoic acid (BA) has been characterized crystallographically. Two beta-CDs cocrystallize with two BAs, 0.7 ethanol and 20.65 water molecules [2(C(6)H(10)O(5))(7).2(C(7)H(6)O(2)).0.7(C(2)H(6)O).20.65H(2)O] in the triclinic space group P1 with unit cell constants: a=15.210(1), b=15.678(1), c=15.687(1) A, alpha=89.13(1), beta=74.64(1), gamma=76.40(1) degrees. The anisotropic refinement of 1840 atomic parameters against 16,201 X-ray diffraction data converged at R=0.078. In the crystal lattice, beta-CD forms dimers stabilized by direct O-2(m)_1/O-3(m)_1...O-2(n)_2/O-3(n)_2 hydrogen bonds (intradimer) and by indirect O-6(m)_1...,O-6(n)_2 hydrogen bonds with one or two bridging water molecules joined in between (interdimer). These dimers are stacked like coins in a roll constructing endless channels where the guest molecules are included. The BA molecules protrude with their COOH groups at the beta-CD O-6-sides and are maintained in positions by hydrogen bonding to the surrounding O-6-H groups and water molecules. Water molecules (20.65) are distributed over 30 positions in the interstices between beta-CD molecules, except the water sites W-1, W-2 that are located in the channel of the beta-CD dimer. Water site W-2 is hydrogen bonded to the disordered ethanol molecule (occupancy 0.7). PMID:12559746

  5. Biodegradable star polymers functionalized with beta-cyclodextrin inclusion complexes.

    PubMed

    Setijadi, Eki; Tao, Lei; Liu, Jingquan; Jia, Zhongfan; Boyer, Cyrille; Davis, Thomas P

    2009-09-14

    Three-armed biodegradable star polymers made from polystyrene (polySt) and poly (polyethylene glycol) acrylate (polyPEG-A) were synthesized via a "core first" methodology using a trifunctional RAFT agent, created by attaching RAFT agents to a core via their R-groups. The resultant three-armed polymeric structures were well-defined, with polydispersity indices less than 1.2. Upon aminolysis and further reaction with dithiodipyridine (DTDP), these three-armed polymers could be tailored with sulfhydryl and pyridyldisulfide (PDS) end functionalities, available for further reaction with any free-sulfhydryl group containing precursors to form disulfide linkages. Nuclear magnetic resonance (NMR) confirmed that more than 98% of the polymer arms retained integral trithiocarbonate active sites after polymerization. Intradisulfide linkages between the core and the arms conferred biodegradability on the star architectures. Subsequently, the arm-termini were attached to cholesterol also via disulfide linkages. The cholesterol terminated arms were then used to form supramolecular structures via inclusion complex formation with beta-cyclodextrin (beta-CD). The star architectures were found to degrade rapidly on treatment with DL-dithiothereitol (DTT). The star polymers and supramolecular structures were characterized using gel permation chromatography (GPC), static light scattering (SLS), 2D NMR, and fluorescence spectroscopy. PMID:19663421

  6. [Preparation and evaluation of valerian oil-beta-cyclodextrin inclusion complex].

    PubMed

    Si, Qi; Wu, Dan; Cao, Qing-Ri; Cui, Jing-Hao

    2013-07-01

    The aim of this study was to improve the stability and cover the unpleasant odor of valerian oil by preparation of beta-cyclodextrin inclusion complex. The preparation method was established based on the yield of inclusion complex and entrapment efficiency of valerian volatile oil. After that, the formulation and processing parameters were optimized by uniform design table. The formations of inclusion complex were validated by DSC and X-RD method. The stability of valerian oil beta-cyclodextrin inclusion was studied under stressed conditions. In conclusion, relatively high yield of inclusion complex and entrapment efficiency were obtained by saturated solution-ultrasonication method. Inclusion complex yield and entrapment efficiency of the valerian oil were (84.78 +/- 3.23)% and (86.23 +/- 2.48)%, which were prepared under the optimized conditions, respectively. The results of DSC and X-RD were indicated the formation of inclusion complex. The stability of test showed that the valerian oil-beta-cyclodextrin inclusion complex was improved significantly. PMID:24199561

  7. Hydroxymethylnitrofurazone:dimethyl-beta-cyclodextrin inclusion complex: a physical-chemistry characterization.

    PubMed

    Grillo, Renato; Melo, Nathalie Ferreira Silva; Moraes, Carolina Morales; Rosa, André Henrique; Roveda, José Arnaldo Frutuoso; Menezes, Carla M S; Ferreira, Elizabeth Igne; Fraceto, Leonardo Fernandes

    2007-12-01

    Hydroxymethylnitrofurazone (NFOH) is active against Trypanosoma cruzi; however, its low solubility and high toxicity precludes its current use in treatment of parasitosis. Cyclodextrin can be used as a drug carrier system, as it is able to form inclusion (host-guest) complexes with a wide variety of organic (guest) molecules. Several reports have shown the interesting use of modified beta-cyclodextrins in pharmaceutical formulation, to improve the bioavailability of drugs and to decrease their toxicity. The aim of this work was to characterize inclusion complexes formed between NFOH and dimethyl-beta-cyclodextrin (DM-beta-CD) by complexation/release kinetics and solubility isotherm experiments using ultraviolet (UV)-visible spectrophotometry and by the measurement of the dynamics information obtained from T(1) relaxation times and diffusion (DOSY) experiments using nuclear magnetic resonance (NMR) spectroscopy. The complex was prepared at different NFOH and DM-beta-CD molar ratios. The UV-visible measurements were recorded in a spectrophotometer, and NMR experiments were recorded at 20 degrees C on a NMR spectrometer (Varian Inova) operating at 500 MHz. Longitudinal relaxation times were obtained by the conventional inversion-recovery method and the DOSY experiments were carried out using the BPPSTE sequence. The kinetics of complexation revealed that 30 h is enough for stabilization of the NFOH absorbance in presence of cyclodextrin. Solubility isotherm studies show a favorable complexation and increase in solubility when NFOH interacts with cyclodextrin. The analysis of the NMR-derived diffusion coefficients and T(1) relaxation times shows that in the presence of DM-beta-CD, NFOH decreases its mobility in solution, indicating that this antichagasic compound interacts with the cyclodextrin cavity. The release kinetics assays showed that NFOH changes its release profile when in the presence of cyclodextrin due to complexation. This study was focused on the

  8. Preparation, characterization and molecular modeling studies of the inclusion complex of Caffeine with Beta-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Prabu, Samikannu; Swaminathan, Meenakshisundaram; Sivakumar, Krishnamoorthy; Rajamohan, Rajaram

    2015-11-01

    The formation through supramolecular interaction of a host-guest inclusion complex of caffeine (CA) with nano-hydrophobic cavity beta-cyclodextrin (β-CD) is achieved by a physical mixture, a kneading method and a co-precipitation method. The formation of the inclusion complex of CA with β-CD in solution state is confirmed by UV-visible spectrophotometer, fluorescence spectrophotometer and time-resolved fluorescence spectrophotometer. The stoichiometry of the inclusion complex is 1:1; the imidazole ring and pyrimidine ring of caffeine is deeply entrapped in the beta-cyclodextrin as confirmed by spectral shifts. The Benesi-Hildebrand plot is used to calculate the binding constant of the inclusion complex of CA with β-CD at room temperature. The Gibbs free energy change of the inclusion complex process is calculated and the process is found to be spontaneous. The thermal stability of the inclusion complex of CA with β-CD is analyzed using differential scanning calorimetry. The crystal structure modification of a solid inclusion complex is confirmed by scanning electron microscopy image analysis. The formation of the inclusion complex of CA with β-CD in the solid phase is also confirmed by FT-IR and XRD. The formation of the inclusion complex between CA and β-CD, as confirmed by molecular docking studies, is in good relationship with the results obtained through different experimental methods.

  9. A spectroscopic study of the inclusion of azulene by beta- and gamma-cyclodextrins.

    PubMed

    Abou-Zied, Osama K

    2005-11-01

    The inclusion of azulene (AZ) inside the cavities of beta-cyclodextrin (beta-CD) and gamma-cyclodextrin (gamma-CD) was studied using absorption, fluorescence and induced-circular dichroism spectroscopy. The inclusion of AZ into the cavity of beta-CD has a stoichiometry of 1:1, whereas that of AZ/gamma-CD complex is 1:2. The equilibrium constants for the formation of the two complexes were calculated to be 780+/-150 M(-1) for AZ:beta-CD and (4.5+/-0.86)x10(5) M(-2) for AZ:(gamma-CD)(2). The latter is due to a stepwise equilibrium mechanism in which a 1:1 complex is formed with a binding constant of 775 M(-1), followed by the formation of a 1:2 complex with a binding constant of 580 M(-1). The difference between the two binding constant values is slight, indicating an almost equal contribution from each of the gamma-CD molecules to the overall binding in AZ:(gamma-CD)(2). From the induced-circular dichroism spectra, the inclusion of AZ was found to be axial in AZ:beta-CD and nearly axial in AZ:(gamma-CD)(2). PMID:16257721

  10. Structure of PEO-b-PPO-b-PEO Triblock Copolymer Inclusion Complexes with Beta-Cyclodextrin

    NASA Astrophysics Data System (ADS)

    Tsai, Chi-Chun; Cheng, Stephen Z. D.; Lotz, Bernard; Huang, Jin; Chen, Yongming

    2009-03-01

    Inclusion complexes, formed by non-covalent host-guest interactions, have been extensively investigated because they can be useful as building blocks for constructing supramolecular structures. Cyclodextrins (CDs), due to their good water-solubility and ability to include a wide range of guest molecules, have been the most intensively studied host molecules. CDs are shaped like a shallow truncated cone, with a hydrophilic outer surface as well as primary (narrower end) and secondary (wider end) hydroxyl groups on the rim of the molecule. The cavity, which is constructed with alkyl groups and glycosidic oxygen atoms, is hydrophobic and can act as a host for a great variety of hydrophobic molecular guests. A series of host-guest inclusion complexes were prepared with beta-cyclodextrin (beta-CD) and PEO-PPO-PEO triblock copolymers of varying molecular weights and compositions. The middle PPO block of the copolymers can be selectively included by beta-CD to form an inclusion complex while the PEO blocks cannot. These inclusion complexes can further self-assembled into supramolecular structures in aqueous solution. The inclusion complexes and self-assembled supramolecular structures were characterized by Nuclear Magnetic Resonance, X-ray diffraction, and Differential Scanning Calorimetry experimental methods.

  11. [Synergetic taste masking of lipid coating and beta-cyclodextrin inclusion].

    PubMed

    Li, Xue; Guo, Zhen; Hao, Jie-Bing; Li, Biao; Liu, Cong-Biao; Guo, Tao; Li, Hai-Yan; Shi, Sen-Lin; Wang, Liu-Yi; Zhang, Ji-Wen

    2014-03-01

    Paracetamol was used as a model drug in this study to investigate the synergetic effects of lipid coating and beta-cyclodextrin (beta-CD) inclusion for masking the bitter taste of poorly soluble drugs. To control the concentration as low as possible of the free drug which produced a bitter taste, a kinetic model was established to calculate the drug distribution theoretically among the free drug in medium, lipid coated particles and molecular inclusion on the basis of the preparation and characterization of the lipid microspheres, so as to select the proper amount of beta-CD. Finally, the synergetic drug delivery systems were prepared and characterized by 1H nuclear magnetic resonance (1H NMR), molecular simulation and the electronic tongue. As a result, the drug release rate constant (k) of the lipid microspheres coated with octadecanol was determined as 0.001 270 s(-1). Then, the synergetic drug delivery systems were prepared with the ratio of 6.74 : 1 (w/w) for beta-CD and paracetamol. The chemical shift values for the fingerprint peaks of paracetamol all increased and hydrogen bonds were formed between the oxygen on the phenolic hydroxyl group, the nitrogen on the imino in paracetamol and the hydrogens on the hydroxyl groups in beta-CD. The results tested by the electronic tongue indicated that the paracetamol, lipid microspheres, beta-CD inclusion and their mixture showed different taste characteristics, with the bitterness order of the synergetic drug delivery systems approximately lipid microspheres < beta-CD inclusion < paracetamol, which confirmed the synergetic taste masking effects of lipid coating and beta-CD molecular inclusion. In summary, the synergetic taste masking was jointly achieved through the retard of the drug release by the lipid coating and the inclusion of the free paracetamol by beta-CD through hydrogen bonds. PMID:24961113

  12. Inclusion complexes of nabumetone with beta-cyclodextrins: thermodynamics and molecular modelling studies. Influence of sodium perchlorate.

    PubMed

    Goyenechea, N; Sánchez, M; Vélaz, I; Martín, C; Martínez-Ohárriz, M C; González-Gaitano, G

    2001-01-01

    Fluorescence, (1)H-NMR and molecular mechanics have been used to study the inclusion complexes of nabumetone (4,6-methoxy-2-naphthyl-butan-2-one; NAB) with beta-cyclodextrin (beta-CD), randomly methylated-beta (M beta-CD) and hydroxypropyl-beta-cyclodextrins (HP beta-CD). The emission spectrum of NAB shows a maximum whose fluorescence intensity increases with the different beta-CDs growing concentrations. This phenomenon allows calculation of the stability constants at 15, 25, 37 and 45 degrees C. The thermodynamic parameters Delta H degrees and Delta S degrees for the inclusion process were obtained from the temperature dependence of the stability constants. Molecular mechanics calculations, together with proton NMR measurements, for the complex with beta-CD prove that the complex can be formed by penetration through any of the rims, with the naphthalene nucleus included and the substituents outside the cavity. The influence of NaClO(4) in the aforementioned complexes has been analysed by spectrofluorimetric measurements. It has been found that the stability constants for the complexes decrease with the salt concentration; the causes are discussed. PMID:11312537

  13. Controlled synthesis and inclusion ability of a hyaluronic acid derivative bearing beta-cyclodextrin molecules.

    PubMed

    Charlot, Aurélia; Heyraud, Alain; Guenot, Pierre; Rinaudo, Marguerite; Auzély-Velty, Rachel

    2006-03-01

    A new synthetic route to beta-cyclodextrin-linked hyaluronic acid (HA-CD) was developed. This was based on the preparation of a HA derivative selectively modified with adipic dihydrazide (HA-ADH) and a beta-cyclodextrin derivative possessing an aldehyde function on the primary face, followed by their coupling by a reductive amination-type reaction. The CD-polysaccharide was fully characterized in terms of chemical integrity and purity by high-resolution NMR spectroscopy. The complexation ability of the grafted CD was further demonstrated by isothermal titration calorimetry using sodium adamantane acetate (ADAc) and Ibuprofen as model guest molecules. The thermodynamic parameters for the complexation of these negatively charged guest molecules by the beta-CD grafted on negatively charged HA were shown to be largely influenced by the ionic strength of the aqueous medium. PMID:16529430

  14. Separation of drug stereoisomers by the formation of. beta. -cyclodextrin inclusion complexes

    SciTech Connect

    Armstrong, D.W.; Ward, T.J.; Armstrong, R.D.; Beesley, T.E.

    1986-05-30

    For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized ..beta..-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as ..beta..-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of ..beta..-cyclodextrin complexes of propanol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of ..beta..-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiometric drugs. 27 references, 3 figures, 2 tables.

  15. Investigating the inclusion properties of aromatic amino acids complexing beta-cyclodextrins in model peptides.

    PubMed

    Caso, Jolanda Valentina; Russo, Luigi; Palmieri, Maddalena; Malgieri, Gaetano; Galdiero, Stefania; Falanga, Annarita; Isernia, Carla; Iacovino, Rosa

    2015-10-01

    Cyclodextrins are commonly used as complexing agents in biological, pharmaceutical, and industrial applications since they have an effect on protein thermal and proteolytic stability, refolding yields, solubility, and taste masking. β-cyclodextrins (β-CD), because of their cavity size are a perfectly suited complexing agent for many common guest moieties. In the case of peptide-cyclodextrin and protein-cyclodextrin host-guest complexes the aromatic amino acids are reported to be the principal responsible of the interaction. For these reasons, we have investigated the inclusion properties of nine designed tripeptides, obtained permuting the position of two L-alanines (Ala, A) with that of one L-tryptophan (Trp, W), L-phenylalanine (Phe, F), or L-tyrosine (Tyr, Y), respectively. Interestingly, the position of the aromatic side-chain in the sequence appears to modulate the β-CD:peptide binding constants, determined via UV-Vis and NMR spectroscopy, which in turn assumes values higher than those reported for the single amino acid. The tripeptides containing a tyrosine showed the highest binding constants, with the central position in the Ac-AYA-NH2 peptide becoming the most favorite for the interaction. A combined NMR and Molecular Docking approach permitted to build detailed complex models, highlighting the stabilizing interactions of the neighboring amino acids backbone atoms with the upper rim of the β-CD. PMID:25985927

  16. Structure-retention correlation of isomeric bile acids in inclusion high-performance liquid chromatography with methyl beta-cyclodextrin.

    PubMed

    Momose, T; Yamaguchi, Y; Iida, T; Goto, J; Nambara, T

    1998-01-01

    The structure-retention correlation of various C24 bile acid isomers was studied by the addition of methyl beta-cyclodextrin (Me-beta-CD) to mobile phases in reversed-phase high-performance liquid chromatography (HPLC). The compounds examined include a series of monosubstituted bile acids related to cholanoic acids differing from one another in the position and configuration of an oxygen-containing function (hydroxyl or oxo group) at the position C-3, C-6, C-7, or C-12 and the stereochemistry of the A/B-ring fusion (trans 5 alpha-H and cis 5 beta-H) in the steroid nucleus. The inclusion HPLC with Me-beta-CD was also applied to biologically important 4 beta- and 6-hydroxylated bile acids substituted by three to four hydroxyl groups in the 5 beta-steroid nucleus. These bile acid samples were converted into their fluorescence prelabeled 24-pyrenacyl ester derivatives and chromatographed on a Capcell Pak C18 column eluted with methanol-water mixtures in the presence or absence of 5 mM Me-beta-CD. The effects of Me-beta-CD on the retentions of each compound were correlated quantitatively to the decreasing rate of capacity factors and the relative strength of host-guest interactions. On the basis of the retention data, specific and nonspecific hydrogen-bonding interactions between the bile acids and the Me-beta-CD were discussed. PMID:9470179

  17. Ofloxacin/beta-cyclodextrin complexation.

    PubMed

    Koester, L S; Guterres, S S; Le Roch, M; Eifler-Lima, V L; Zuanazzi, J A; Bassani, V L

    2001-07-01

    Ofloxacin (OFX) is a fluorquinolone characterized by photochemical instability. With the goal to improve its photostability in aqueous solutions, the complexation of ofloxacin with beta-cyclodextrin was investigated. The complexes showed a water solubility enhancement of approximately 2.6 times; nevertheless, the photodegradation of ofloxacin was not reduced. The complexes obtained were characterized by thermal and 1H nuclear magnetic resonance (NMR) analysis, which revealed an interaction between ofloxacin and beta-cyclodextrin. The last analysis indicated that only partial inclusion of the N-methylpiperazinyl moiety occurred, which can explain the fact that photostabilization was not improved. This partial inclusion phenomenon could be explained also by computer-aided molecular modeling. PMID:11548860

  18. Characterization of beta-cyclodextrin inclusion complexes containing an essential oil component.

    PubMed

    Abarca, Romina L; Rodríguez, Francisco J; Guarda, Abel; Galotto, María J; Bruna, Julio E

    2016-04-01

    An important issue in food technology is that antimicrobial compounds can be used for various applications, such as the development of antimicrobial active packaging materials. Yet most antimicrobial compounds are volatile and require protection. In the present study, the inclusion complexes of 2-nonanone (2-NN) with β-cyclodextrin (β-CD), were prepared by a co-precipitation method. Entrapment efficiency (EE), thermal analysis (DSC and TGA), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR), sorption isotherms and antifungal activity were evaluated for the characterization of the inclusion complex (β-CD:2-NN). A higher EE was obtained (34.8%) for the inclusion complex 1:0.5 than for other molar rates. Both DSC and TGA of the inclusion complexes showed the presence of endothermic peaks between 80 °C and 150 °C, attributed to a complexation phenomenon. Antimicrobial tests for mycelial growth reduction under atmospheric conditions proved the fungistatic behaviour of the inclusion complexes against Botrytis cinerea. PMID:26593579

  19. A new crystal form of beta-cyclodextrin-ethanol inclusion complex: channel-type structure without long guest molecules.

    PubMed

    Aree, Thammarat; Chaichit, Narongsak

    2003-07-22

    A new crystal form of beta-cyclodextrin (beta-CD)[bond]ethanol[bond]dodecahydrate inclusion complex [(C(6)H(10)O(5))(7).0.3C(2)H(5)OH.12H(2)O] belongs to monoclinic space group C2 (form II) with unit cell constants a=19.292(1), b=24.691(1), c=15.884(1) A, beta=109.35(1) degrees. The beta-CD macrocycle is more circular than that of the complex in space group P2(1) [form I: J. Am. Chem. Soc. 113 (1991) 5676]. In form II, a disordered ethanol molecule (occupancy 0.3) is placed in the upper part of beta-CD cavity (above the O-4 plane) and is sustained by hydrogen bonding to water site W-2. In form I, an ethanol molecule located below the O-4-plane is well ordered because it hydrogen bonds to surrounding O-3[bond]H, O-6[bond]H groups of the symmetry-related beta-CD molecules. In the crystal lattice of form I, beta-CD macrocycles are stacked in a typical herringbone cage structure. By contrast, the packing structure of form II is a head-to-head channel that is stabilized at both O-2/O-3 and O-6 sides of each beta-CD by direct O(CD)...O(CD) and indirect O(CD)...O(W)...(O(W))...O(CD) hydrogen bonds. The 12 water molecules are disordered in 18 positions both inside the channel-like cavity of beta-CD dimer (W-1[bond]W-6) and in the interstices between the beta-CD macrocycles (W-7[bond]W-18). The latter forms a cluster that is hydrogen bonded together and to the neighboring beta-CD O[bond]H groups. PMID:12860429

  20. Crystal form III of beta-cyclodextrin-ethanol inclusion complex: layer-type structure with dimeric motif.

    PubMed

    Aree, Thammarat; Chaichit, Narongsak

    2008-09-01

    The crystal form III of the beta-cyclodextrin (beta-CD)-ethanol inclusion complex [2(C(6)H(10)O(5))(7).1.5C(2)H(5)OH.19H(2)O] belongs to the triclinic space group P1 with unit cell constants: a=15.430(1), b=15.455(1), c=17.996(1)A, alpha=99.30(1) degrees , beta=113.18(1) degrees , gamma=103.04(1) degrees . beta-CD forms dimers comprising two identical monomers that adopt a 'round' conformation stabilized by intramolecular, interglucose O-3(n)cdots, three dots, centeredO-2(n+1) hydrogen bonds. The two beta-CD monomers of form III are isostructural to that of form I in the monoclinic space group P2(1) [Steiner, T.; Mason, S. A.; Saenger, W. J. Am. Chem. Soc.1991, 113, 5676-5687], but exhibit a striking difference from that of form II in the monoclinic space group C2 [Aree, T.; Chaichit, N. Carbohydr. Res.2003, 338, 1581-1589]. The small guest EtOH molecule orients differently in the large beta-CD cavity. In form III, two disordered EtOH molecules are embedded in the beta-CD-dimer cavity. A half occupied EtOH molecule (#1) is located above the O-4 plane of beta-CD #1, whereas another doubly disordered EtOH molecule (#2, #3) is situated at about the middle of the beta-CD-dimer cavity. The three EtOH sites are maintained in positions by making van der Waals contacts to each other and to the surrounding water sites and beta-CD O-3-H group. The EtOH molecules disordered (occupancy 0.3) above the beta-CD O-4 plane in form I and fully occupied beneath the O-4 plane in form II are strongly held in positions by hydrogen bonding with the surrounding water site and beta-CD O-6-H, O-3-H groups. Occurrence of the beta-CD dimer as a structural motif of channel-type packing (form II) and layer-type packing (form III) is attributed to the higher tendency for self aggregation under the moderate acidic conditions. At weak acidic conditions, beta-CD prefers a herringbone mode (form I). PMID:18490008

  1. Improvement of dissolution properties of a new Helicobacter pylori eradicating agent (TG44) by inclusion complexation with beta-cyclodextrin.

    PubMed

    Anzai, Kinsei; Mizoguchi, Jun-ichi; Yanagi, Toshiharu; Hirayama, Fumitoshi; Arima, Hidetoshi; Uekama, Kaneto

    2007-10-01

    The interaction of a newly developed Helicobacter pylori eradicating agent (TG44, 4-methylbenzyl-4'-[trans-4-(guanidinomethyl)cyclohexylcarbonyloxy]biphenyl-4-carboxlylate monohydrochloride) with beta-cyclodextrin (beta-CyD) in aqueous solution and in solid state was studied to gain insight into the high in-vivo H. pylori eradicating activity of TG44/beta-CyD complex. The interaction was studied by the solubility method, spectroscopic methods, powder X-ray diffractometry and differential scanning colorimetry (DSC). TG44 gave A(L)-type phase solubility diagram with beta-CyD in water, showing a linear increase in solubility of the drug up to 8 mM beta-CyD concentration. The solubility of TG44 (0.04 mM in water at 25 degrees C) increased about 70-folds at 8 mM beta-CyD. Ultraviolet, circular dichroism, fluorescence and (1)H-nuclear magnetic resonance spectroscopic studies indicated that TG44 forms the inclusion complex with beta-CyD in a 1:1 stoichiometry and the biphenyl moiety of TG44 is preferably included in the beta-CyD cavity in water. The Giordano plot made by monitoring changes in the fusion enthalpy of TG44 (about 184 degrees C) suggested that TG44 forms the 1:1 complex with beta-CyD in the solid state. The TG44/beta-CyD solid complex in a 1:1 stoichiometry was prepared by the grinding and spray-drying methods and confirmed by powder X-ray diffractometry and DSC that the complex is in an amorphous state. The initial dissolution rate of TG44/beta-CyD complex was significantly faster than those of the drug alone and the physical mixture of both components, maintaining higher supersaturated concentrations of the drug for a long time. The results suggested that the higher eradicating activity of TG44/beta-CyD complex to Helicobacter pylori, compared with that of the drug alone, is attributable at least partly to the faster dissolving property of the complex and its ability to maintain the supersaturated state of the drug in the gastric fluid. PMID:17917290

  2. Biosynthesis of ketomycin. (II) biomimetic model for beta-lactamase catalysis: host-guest interactions in cyclodextrin-penicillin inclusion complex

    SciTech Connect

    Mak, H.W.

    1986-01-01

    The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid. Phenylalanine and 2',5'-dihydrophenylalanine derived from shikimic acid are not intermediates in the biosynthesis. Degradation of ketomycin derived from (1,6-/sup 14/C)shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexane ring of ketomycin. The resistance of pathogenic bacteria to the action of ..beta..-lactam antibiotics is mainly ascribed to their ability to produce ..beta..-lactamase to cleave the ..beta..-lactam ring. It is essential to understand the molecular nature of ..beta..-lactamase-penicillin recognition for designing and formulating more effective ..beta..-lactam antibiotics. A biomimetic study of ..beta..-lactamase is therefore initiated. To meet the requirements of hydrophobic and serine protease characteristics of ..beta..-lactamase, ..cap alpha..-cyclodextrin is chosen as a biomimetic model for ..beta..-lactamase. The structural specificity and the chemical dynamics of ..cap alpha..-cyclodextrin-phenoxymethyl penicillin inclusion complex in solid state and in solution have been determined by IR and NMR spectroscopy. The spectral results strongly indicate that the phenyl portion of the phenoxymethyl penicillin forms a stable inclusion complex with the hydrophobic cavity of ..cap alpha..-cyclodextrin in solution as well as in the solid state. Kinetic studies followed by /sup 1/HNMR and HPLC analyses under alkaline condition have shown that the ..cap alpha..-cyclodextrin mimics the catalytic function of serine of ..beta..-lactamase in the stereospecific hydrolysis of the ..beta..-lactam ring of phenoxymethyl penicillin.

  3. Inclusion complexes of cypermethrin and permethrin with monochlorotriazinyl-beta-cyclodextrin: A combined spectroscopy, TG/DSC and DFT study

    NASA Astrophysics Data System (ADS)

    Yao, Qi; You, Bin; Zhou, Shuli; Chen, Meng; Wang, Yujiao; Li, Wei

    2014-01-01

    The suitable size hydrophobic cavity and monochlorotriazinyl group as a reactive anchor make MCT-β-CD to be widely used in fabric finishing. In this paper, the inclusion complexes of monochlorotriazinyl-beta-cyclodextrin (MCT-β-CD) with cypermethrin (CYPERM) and permethrin (PERM) are synthesized and analyzed by TG/DSC, FT-IR and Raman spectroscopy. TG/DSC reveals that the decomposed temperatures of inclusion complexes are lower by 25-30 °C than that of physical mixtures. DFT calculations in conjunction with FT-IR and Raman spectral analyses are used to study the structures of MCT-β-CD and their inclusion complexes. Four isomers of trisubstituted MCT-β-CD are designed and DFT calculations reveal that 1,3,5-trisubstituted MCT-β-CD has the lowest energy and can be considered as main component of MCT-β-CD. The ground-state geometries, vibrational wavenumbers, IR and Raman intensities of MCT-β-CD and their inclusion complexes were calculated at B3LYP/6-31G (d) level of theory. Upon examining the optimized geometry of inclusion complex, we find that the CYPERM and PERM are inserted into the toroid of MCT-β-CD from the larger opening. The band at 1646 cm-1 in IR and at 1668 cm-1 in Raman spectrum reveals that monochloroazinyl group of MCT-β-CD exists in ketone form but not in anion form. The noticeable IR and Raman shift of phenyl reveals that these two benzene rings of CYPERM and PERM stays inside the cavity of MCT-β-CD and has weak interaction with MCT-β-CD. This spectroscopy conclusion is consistent with theoretical predicted structure.

  4. Synthesis and spectroscopy studies of the inclusion complex of 3-amino-5-methyl pyrazole with beta-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Louiz, S.; Labiadh, H.; Abderrahim, R.

    2015-01-01

    Amino pyrazole belongs to anti-inflammatory class, and is characterized by a low solubility in water. (In order to increase its solubility in water, inclusion complex of amino pyrazole with β-CD was obtained.) The inclusion complex obtained between AMP and β-cyclodextrin, was characterized by FT-IR, 1H NMR, 1H-1H NOESY, 13C NMR, DEPT, XHCOR, spectra, through TG analysis, DTA, DSC and Scanning Electron Microscopy (SEM). The stoichiometry of inclusion complex is 1:1 (guest-host) and K stability is 1.1 × 104 M-1.

  5. Spectroscopic and theoretical study on inclusion complexation of beta-cyclodextrin with permethrin

    NASA Astrophysics Data System (ADS)

    Li, Wei; Lu, Bitai; Sheng, Aiguo; Yang, Feng; Wang, Zhendong

    2010-09-01

    Due to the poor water solubility of permethrin (PERM), an inclusion technique has been developed to modify its physical and chemical properties so as to improve its function finishing properties. In this paper, the inclusion complex of permethrin (PERM) and β-CD was synthesized and characterized. To reveal the inclusion mechanism, FT-IR and Raman spectrum analyses in conjugation with DFT calculations were performed on PERM, β-CD and β-CD·PERM inclusion complex. The ground-state geometries, vibrational wavenumbers, IR and Raman intensities were calculated by DFT at B3LYP/6-31G (d) level. The calculated mean bond lengths of glucose units for β-CD and β-CD·PERM inclusion complex are longer by 0.005-0.029 Å and 0.002-0.025 Å than those of the XRD structure of β-CD·11H 2O inclusion complex, respectively. Upon examining the optimized geometry of inclusion complex, we notice that a PERM molecule is inserted into the toroid of β-CD from the larger opening. Calculated vibrational wavenumbers are calibrated and compared with experimental fundamentals and the errors are within 20 cm -1. The significant changes on Raman spectrum of PERM, when it is encapsulated by β-CD, in combination with normal mode analysis reveal that the ring A of PERM penetrates through the toriod of β-CD and is exposed to the outside of the cavity, but the ring B is inside the cavity. The good agreements between predicted spectra and experimental ones prove that the theoretical predicted geometries are correct and accord with the real structures.

  6. Study of angiotensin-(1-7) vasoactive peptide and its beta-cyclodextrin inclusion complexes: complete sequence-specific NMR assignments and structural studies.

    PubMed

    Lula, Ivana; Denadai, Angelo L; Resende, Jarbas M; de Sousa, Frederico B; de Lima, Guilherme F; Pilo-Veloso, Dorila; Heine, Thomas; Duarte, Hélio A; Santos, Robson A S; Sinisterra, Rubén D

    2007-11-01

    We report the complete sequence-specific hydrogen NMR assignments of vasoactive peptide angiotensin-(1-7) (Ang-(1-7)). Assignments of the majority of the resonances were accomplished by COSY, TOCSY, and ROESY peak coordinates at 400MHz and 600MHz. Long-side-chain amino acid spin system identification was facilitated by long-range coherence transfer experiments (TOCSY). Problems with overlapped resonance signals were solved by analysis of heteronuclear 2D experiments (HSQC and HMBC). Nuclear Overhauser effects (NOE) results were used to probe peptide conformation. We show that the inclusion of the angiotensin-(1-7) tyrosine residue is favored in inclusion complexes with beta-cyclodextrin. QM/MM simulations at the DFTB/UFF level confirm the experimental NMR findings and provide detailed structural information on these compounds in aqueous solution. PMID:17904691

  7. Supramolecular Inclusion in Cyclodextrins: A Pictorial Spectroscopic Demonstration

    ERIC Educational Resources Information Center

    Haldar, Basudeb; Mallick, Arabinda; Chattopadhyay, Nitin

    2008-01-01

    A spectroscopic experiment is presented that reveals that the hydrophobically end-modified water-soluble polymeric fluorophore, pyrene end-capped poly(ethylene oxide) (PYPY), interacts differently with [alpha], [beta], and [gamma]-cyclodextrins (CD) to form supramolecular inclusion complexes. The emission spectrum of PYPY in aqueous solution shows…

  8. Improvement of water solubility and in vitro dissolution rate of aceclofenac by complexation with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin.

    PubMed

    Ranpise, Nisharani S; Kulkarni, Nilesh S; Mair, Parth D; Ranade, Arati N

    2010-01-01

    The present study deals with the inclusion complexation of aceclofenac with beta-cyclodextrin by grinding, microwave and spray-drying techniques. A derivative of beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, was also subjected to the complexation process with aceclofenac by spray-drying technique. The samples were subjected to in-vitro dissolution studies, fourier transform infra-red spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy and x-ray diffraction studies. The in-vitro dissolution of aceclofenac-hydroxypropyl-beta-cyclodextrin complex was faster as compared to the aceclofenac- beta-cyclodextrin complex and aceclofenac alone. Spray-dried aceclofenac-beta-cyclodextrin complex were subjected to anti-inflammatory and analgesic activity and showed significant anti-inflammatory and analgesic activity. PMID:19505225

  9. The inclusion complex of rosmarinic acid into beta-cyclodextrin: A thermodynamic and structural analysis by NMR and capillary electrophoresis.

    PubMed

    Aksamija, Amra; Polidori, Ange; Plasson, Raphaël; Dangles, Olivier; Tomao, Valérie

    2016-10-01

    This work focuses on the characterization of the rosmarinic acid (RA)-β-cyclodextrin (CD) complex in aqueous solution by (1)H NMR (1D- and 2D-ROESY), completed with studies by capillary electrophoresis (CE). From the (1)H NMR data, the stoichiometry of the complex was determined by a Job's plot and the binding constant was estimated from a linear regression (Scott's method). At pH 2.9, the results showed that RA binds CD with a 1:1 stoichiometry and a binding constant Kb of 445 (±53) M(-1) or 465 (±81) M(-1) depending on the CD protons (H-5 or H-3) selected for the evaluation. The Kb value was also calculated from the CD-induced chemical shifts of each RA proton in order to collect information on the structure of the complex. The pH dependence of Kb revealed that the RA carboxylic form displays the highest affinity for CD. An investigation by capillary electrophoresis fully confirmed these results. 2D ROESY analysis provided detailed structural information on the complex and showed a strong correlation between H-3 and H-5 of CD and most RA protons. In conclusion, RA, an efficient phenolic antioxidant from rosemary with a marketing authorization, spontaneously forms a relatively stable inclusion complex with CD in water. PMID:27132848

  10. Optical properties and inclusion of an organic fluorophore in organized media of micellar solutions and beta-cyclodextrin

    NASA Astrophysics Data System (ADS)

    El-Sayed, Yusif S.

    2013-02-01

    In this study, we prepared a new chalcone compound (3-(4'-diethylaminophenyl)-1-(2-pyridinyl) prop-2-en-1-one abbreviated as DEAPPP) and examined its characterization and photophysical properties such as singlet absorption, molar absorptivity, fluorescence spectra, and fluorescence quantum yield (ϕf). DEAPPP dye exhibited a large red shift in both absorption and emission spectra as solvent polarity increases, indicating a large change in dipole moment of molecule upon excitation. Also, the fluorescence quantum yield was solvent dependent. The absorption and fluorescence emission spectral properties of DEAPPP have been investigated in organized media of aqueous micellar and β-cyclodextrin (CD) solutions. While the absorption spectra were less sensitive to the nature of the added surfactant or CD, the characteristics of the intramolecular charge transfer (ICT) fluorescence were highly sensitive to the properties of the medium. The ICT maximum was strongly blue-shifted with a great enhancement in the fluorescence quantum yield on adding micellar or CD. This indicated that the solubilization of DEAPPP increased in the micellar core and an inclusion complex with β-CD was formed. The critical micelle concentration (CMC) as well as the polarity of the micellar core of sodium dodecyl sulfate (SDS), Cetyltrimethylammonium bromide (CTAB) and Triton X-100 (TX-100) have been determined. The CMC values were in good agreement with the reported values while the polarity was lower indicating that DEAPPP molecules were incorporated in the micellar core not at the micellar interface. The binding constants of DEAPPP: micelles or DEAPPP: CD complexes have been also determined.

  11. Some properties and the inclusion behavior of three positional isomers of 6(1),6n-di-O-alpha-D-glucosyl-cyclomaltoheptaoses (beta-cyclodextrins).

    PubMed

    Okada, Y; Koizumi, K

    1998-02-01

    Three positional isomers of 6(1),6n-di-O-alpha-D-glucosyl-cyclomaltoheptaose [1,n-(G)2-beta CDs; n = 2-4] which existed in the digests with glucoamylase of the products from cyclomaltoheptaose (beta-cyclodextrin, beta CD) and maltose with Klebsiella pneumoniae pullulanase, were purified by HPLC. The solubilities of two isomers of those doubly branched beta CDs, 1,2- and 1,3-(G)2-beta CDs, in water were much higher than those of parent non-branched beta CD and mono-branched beta CD, 6-O-alpha-D-glucosyl-beta CD (G-beta CD), while the solubility of another isomer, 1,4-(G)2-beta CD, was significantly lower than these two isomers, though it was higher than that of beta CD. On the other hand, the solubilities of 1,2- and 1,3-isomers in 10, 30, and 50% (v/v) aqueous methanol at 25 degrees C were independent of methanol concentrations and their solubilities were the same as those in water at 25 degrees C. However, that of 1,4-isomer increased with increasing methanol concentrations. The hemolytic activities of 1,n-(G)2-beta CDs on human erythrocytes in isotonic solution were lower than those of G-beta CD and beta CD, and became weaker in the order of 1,4- > 1,2- > 1,3-isomers. The complex-forming abilities of 1,n-(G)2-beta CDs for digitoxin, digoxin, fluorometholone, flurbiprofen, hydrocortisone acetate, and norfloxacin were about the same as those of beta CD and G-beta CD, whereas reserpine was more difficult to include within 1,n-(G)2-beta CDs than beta CD and G-beta CD. Nevertheless, the solubilities of those guest compounds were much more enhanced by 1,n-(G)2-beta CDs and G-beta CD than by beta CD. PMID:9501468

  12. Preparation and characterization of albendazole beta-cyclodextrin complexes.

    PubMed

    Castillo, J A; Palomo-Canales, J; Garcia, J J; Lastres, J L; Bolas, F; Torrado, J J

    1999-12-01

    Albendazole (ABZ), mebendazole (MBZ), and ricobendazole (RBZ) are low-soluble anthelmintic benzimidazole carbamate drugs. To increase their aqueous solubility, three different types of beta-cyclodextrins (CyDs): beta-cyclodextrin (CD), hydroxypropyl-beta-cyclodextrin (HPCD), and methyl-beta-cyclodextrin (MCD) were used. Solubility depended on the type of CyDs. Increased solubility was obtained when the more substituted CyDs (HPCD or MCD) were used instead of nonsubstituted CD. Stability constants were calculated assuming a 1:1 stoichiometry. Calculated stability constant values depended on initial solubility of drug and pH of the medium. Solid ABZ complexes were prepared by coprecipitation and freeze-drying methods. These products were compared with physical mixtures of ABZ and CyDs. The characterization of these products was made by differential scanning calorimetry (DSC) and drug release studies. True inclusion complexes were obtained only by the freeze-drying method. Drug release studies showed that the freeze-dried inclusion complexes increased the solubility rate of ABZ, although a supersaturation effect was observed when drug release studies were performed in nonsink conditions. A bioavailability study on mice was done with a formulation of ABZ:HPCD complex and was compared to a conventional ABZ suspension. A significantly (p < .05) shorter Tmax of absorption was obtained by using the complex formulation. Greater and significant (p < .05) differences for AUC and Cmax were observed. PMID:10612019

  13. Combining NMR and molecular modelling in a drug delivery context: investigation of the multi-mode inclusion of a new NPY-5 antagonist bromobenzenesulfonamide into beta-cyclodextrin.

    PubMed

    Uccello-Barretta, Gloria; Balzano, Federica; Sicoli, Giuseppe; Fríglola, Carmen; Aldana, Ignacio; Monge, Antonio; Paolino, Donatella; Guccione, Salvatore

    2004-01-15

    NMR spectroscopic and molecular modelling methods have been employed to describe the complexation of trans-N-4-[N'-(4-chlorobenzoyl)hydrazinocarbonyl]cyclohexylmethyl-4-bromobenzenesulfonamide, a new chemotype of NPY-5 antagonist, and beta-cyclodextrin, revealing the coexistence of two different kinds of 1:1 complexes where conformational changes of the guest compound with respect to the free state are also detected. PMID:14723963

  14. Computational study on the molecular inclusion of andrographolide by cyclodextrin.

    PubMed

    Zhou, Hongwei; Lai, Wai-Ping; Zhang, Zhiqiang; Li, Wai-Kee; Cheung, Hon-Yeung

    2009-03-01

    Due to the poor water solubility of andrographolide (andro), an inclusion technique has been developed to modify its physical and chemical properties so as to improve its bioavailability. In contrast with the immense experimental studies on the inclusion complexes of andro:cyclodextrin, no computational study has so far been carried out on this system. In this work, preliminary docking experiments with AutoDock were performed. Density Functional Theory (DFT) and Austin Model 1 (AM1) calculations upon the docking instances were applied to investigate the two possible modes of molecular inclusions between andro and x-cyclodextrin (xCD, where x is alpha, beta or gamma). Atoms-in-Molecules (AIM) analysis based on the B3LYP/cc-pVDZ wavefunction was applied to verify the existence of the intermolecular hydrogen bonds. It was found that the most stable complex among the six possible inclusion complexes was the one formed between andro and betaCD with andro's decalin ring moiety wrapped by CD at a ratio of 1:1. The hydrogen bonds between andro and CD were responsible for the stability of the inclusion complexes. The calculated data were found to be consistent with the experimental results. Thus, the results of this study can aid new drug design processes. PMID:18841328

  15. Temperature Dependence of Positron Annihilation in beta-Cyclodextrin and beta-Cyclodextrin Complexes

    NASA Astrophysics Data System (ADS)

    Hu, Y.; Hsu Hadley, F. H., Jr.; Trinh, T.

    1996-11-01

    The effects of temperature on positron annihilation in beta-cyclodextrin and beta-cyclodextrin complexed with benzyl salicylate, benzyl acetate, ethyl salicylate, geraniol, linalool and nerol were studied. Samples were prepared by slurry, air-dried and freeze-dried methods. Lifetime spectra were measured as a function of temperature for each sample. Comparison of the annihilation rate and intensity of the longer-lived component showed that positronium formation was affected by guest molecules, preparation methods and temperature variations. Results can be used to explain beta-cyclodextrin complex formation with different guest molecules.

  16. [Pharmaceutical applications of sulfobuthylether-beta-cyclodextrin].

    PubMed

    Sebestyén, Zita; Szepesi, Katalin; Szabó, Barnabás

    2013-01-01

    Sulfobuthylether-beta-cyclodextrin (SBECD) is a substituted derivative of a cyclic oligosaccharide containing seven glucopyranose units, which bear pH-independent negative charges because of sulfonate groups. This derivative has better solubility and toxicological characteristics than the unsubstituted beta-cyclodextrin, and the presence of sulfobuthyl groups opens new dimensions in the interactions acting the part of the complex formation. These create opportunities for the pharmaceutical applications of this compound. Currently six pharmaceutical preparations circulate--moiety of these circulates in Hungary also--which have a composition containing SBECD as pharmaceutical excipient. Out of the main effects of the complex-forming agent the solubility enhancement is utilized in these compositions to achieve the solution of a therapeutic dose in the case of intravascular administration. Available experimental evidences and published patents are indicative of broadening the circle of the applications in point of both technological advantages and dosage forms. PMID:23926650

  17. Host-guest interaction of L-tyrosine with beta-cyclodextrin.

    PubMed

    Shanmugam, M; Ramesh, D; Nagalakshmi, V; Kavitha, R; Rajamohan, R; Stalin, T

    2008-11-01

    The inclusion complexes of beta-cyclodextrin (beta-CD) with L-tyrosine (L-TYN) were investigated by using spectrophotometers. The absorption and fluorescence enhancement occurs with beta-CD and L-TYN forms 1:1 inclusion complex. The unusual blue shift of hydroxyl ion in the beta-CD medium confirms OH groups present in the interior part of the beta-CD cavity and -COOH group present in the upper part of the beta-CD cavity. A mechanism is proposed to explain inclusion process. The inclusion interaction was examined and the thermodynamic parameters of inclusion process DeltaG, DeltaH and DeltaS were determined. The results indicated that the inclusion process was an exergonic and spontaneous process. Stable solid inclusion complexes were established and characterized by FT-IR, scanning electron microscope (SEM) methods. PMID:18243779

  18. pH dependent in-out isomerism of an amino-beta-cyclodextrin derivative.

    PubMed

    Alcalde, Mercedes Alvarez; Gancedo, Cristina; Jover, Aida; Carrazana, Jorge; Soto, Victor H; Meijide, Francisco; Tato, José Vazquez

    2006-07-13

    An amino derivative of beta-cyclodextrin [6-(6-aminehexanamide)-6-deoxy)-beta-cyclodextrin (6-betaCD)] was synthesized, and the formation of an intramolecular inclusion complex was studied by NMR techniques. The deprotonation/protonation of the amino group stimulates an in/out movement of the pendant group toward/from the cyclodextrin cavity, the protonated species lying outside the hydrophobic cyclodextrin cavity but the unprotonated one residing inside and outside the cavity. The protonation of the amino group is a fast exchange rate NMR time-scale process, but the chain movement is a slow one. The equilibrium constants of both processes were determined from 1H NMR experiments and the kinetic constants for the slow process were determined from exchange spectroscopy (EXSY) experiments. PMID:16821861

  19. Interaction of ochratoxin A with quaternary ammonium beta-cyclodextrin.

    PubMed

    Poór, Miklós; Kunsági-Máté, Sándor; Szente, Lajos; Matisz, Gergely; Secenji, Györgyi; Czibulya, Zsuzsanna; Kőszegi, Tamás

    2015-04-01

    Ochratoxin A (OTA) is a widely spread nephrotoxic food contaminant mycotoxin. Unfortunately, attenuation or prevention of the toxic effects of OTA is still an unresolved problem. Molecular inclusion of OTA by cyclodextrins (CDs) results in complexes with low stability. In the human organism, OTA exists mostly in the dianionic state (OTA(2-)). Therefore, our major goal was to develop a chemically modified cyclodextrin which gives a more stable complex with OTA than the previously published derivatives and which shows stronger preference towards OTA(2-). In our fluorescence spectroscopic study we demonstrate that quaternary ammonium beta-cyclodextrin (QABCD) fulfils both of these requirements. The calculated stability constant of the QABCD-OTA(2-) complex was 28,840 M(-1) (about 200-fold higher than that of the β-CD-OTA(2-) complex). We hypothesize, that QABCD may be a suitable tool for the decontamination of different OTA-contaminated drinks; furthermore, for alleviation of the toxic effects of OTA, such complex formation may reduce its absorption from the intestine. PMID:25442535

  20. Preparation and Characterization of Pioglitazone Cyclodextrin Inclusion Complexes

    PubMed Central

    Pandit, V; Gorantla, R; Devi, K; Pai, RS; Sarasija, S

    2011-01-01

    Pioglitazone, a class II Biopharmaceutical Classification System drug having poor water solubility and slow dissolution rate may have a negative impact on its subtherapeutic plasma drug levels leading to therapeutic failure. In order to improve its water solubility and thus dissolution, cyclodextrin complexation technique was followed. The phase solubility studies were carried using three different types of cyclodextrins viz., β, methyl-β and γ-cyclodextrins. The Gibbs free energy was calculated in order to determine ease of the complexation. Binary systems of pioglitazone with cyclodextrins were prepared by kneading method and spray drying method. The phase solubility profiles with all the three cyclodextrins were classified as AL-type, indicating the formation of 1:1 stoichiometric inclusion complexes. The complexation capability of cyclodextrins with pioglitazone increased in the order of methyl-β > β > γ-cyclodextrin. The Gibbs free energy was found to be in the order γ > methyl-β > β cyclodextrin. Characterization of inclusion complexes was done by solubility studies, in vitro dissolution studies, Fourier transformation-infrared spectroscopy, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry studies. Inclusion complexes exhibited higher rates of dissolution than the corresponding physical mixtures and pure drug. Greater solubility was observed with spray-dried methyl-β cyclodextrin complexes (2.29 ± 0.001 mg/ml) in comparison to the kneaded methyl-β cyclodextrin complexes (1.584 ± 0.053 mg/ml) and pure drug (0.0714 ± 0.0018 mg/ml). PMID:22224032

  1. Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:beta-cyclodextrin complex.

    PubMed

    Bilensoy, Erem; Rouf, M Abdur; Vural, Imran; Sen, Murat; Hincal, A Atilla

    2006-01-01

    The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility, clotrimazole was incorporated as its inclusion complex with 1:1 molar ratio with beta-cyclodextrin. The inclusion complex was thoroughly characterized using various techniques, including 1H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and determination of stability constant (k(1:1)). The gelation temperature and rheological behavior of different formulations at varying temperatures were measured. In vitro release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with beta-cyclodextrin, inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with formulations containing drug:cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release thermosensitive and mucoadhesive vaginal gel was determined to be clotrimazole:beta-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing continuous and prolonged release of active material above MIC values. PMID:16796356

  2. Interaction of beta-cyclodextrin with cadmium(II) ions.

    PubMed

    Norkus, Eugenijus; Grinciene, Giedre; Vuorinen, Tapani; Vaitkus, Rimantas; Butkus, Eugenijus

    2003-12-01

    Reduction of Cd(II) on a dropping mercury electrode was used to study interaction of beta-cyclodextrin with Cd(II) ions. It was found that Cd(II) forms Cdbeta-CD(OH)(2)(2-) hydroxy-complex with the anion of beta-cyclodextrin in alkaline solutions (pH>11), the logarithm of stability constant being 10.4+/-0.1 (20 degrees C; I=1.0). The calculated value of the diffusion coefficient equal to 1.0x10(-6)cm(2)/s shows a large size Cd(II) complex species formation in alkaline solutions containing beta-CD. PMID:14607371

  3. Studying on inclusion complexes of Wogonin with β-cyclodextrin and hydroxypropyl-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Li, Jinxia; Chao, Jianbin; Zhang, Min

    2012-02-01

    The formation of the complexes of Wogonin with β-cyclodextrin (β-CD) and hydroxypropyl-cyclodextrin (HP-β-CD) was studied by fluorescence spectra and nuclear magnetic resonance spectroscopy (NMR). The formation constants (Ks) of complexes were determined by fluorescence method. The results suggested that HP-β-CD was easier to form inclusion with Wogonin than β-CD in solution. In different pH solutions, CDs have different inclusive capacity to Wo. β-CD was most suitable for inclusion of neutral form and HP-β-CD was suitable for acidic form. In addition, the experimental resulted confirmed the existence of 1:1 inclusion complex of Wogonin with CDs. Besides, kinetic studies of DPPH rad with Wogonin and CDs complexes were done. The results obtained indicated that the complex was the most reactive form. Special configuration of complex has been proposed on NMR technique.

  4. Poly(l-Lactic Acid)/Gelatin Fibrous Scaffold Loaded with Simvastatin/Beta-Cyclodextrin-Modified Hydroxyapatite Inclusion Complex for Bone Tissue Regeneration.

    PubMed

    Lee, Jung Bok; Kim, Ji Eun; Balikov, Daniel A; Bae, Min Soo; Heo, Dong Nyoung; Lee, Donghyun; Rim, Hyun Joon; Lee, Deok-Won; Sung, Hak-Joon; Kwon, Il Keun

    2016-07-01

    Recently, the application of nanostructured materials in the field of tissue engineering has garnered attention to mediate treatment and regeneration of bone defects. In this study, poly(l-lactic acid) (PLLA)/gelatin (PG) fibrous scaffolds are fabricated and β-cyclodextrin (βCD) grafted nano-hydroxyapatite (HAp) is coated onto the fibrous scaffold surface via an interaction between βCD and adamantane. Simvastatin (SIM), which is known to promote osteoblast viability and differentiation, is loaded into the remaining βCD. The specimen morphologies are characterized by scanning electron microscopy. The release profile of SIM from the drug loaded scaffold is also evaluated. In vitro proliferation and osteogenic differentiation of human adipose derived stem cells on SIM/HAp coated PG composite scaffolds is characterized by alkaline phosphatase (ALP) activity, mineralization (Alizarin Red S staining), and real time Polymerase chain reaction (PCR). The scaffolds are then implanted into rabbit calvarial defects and analyzed by microcomputed tomography for bone formation after four and eight weeks. These results demonstrate that SIM loaded PLLA/gelatin/HAp-(βCD) scaffolds promote significantly higher ALP activity, mineralization, osteogenic gene expression, and bone regeneration than control scaffolds. This suggests the potential application of this material toward bone tissue engineering. PMID:26996294

  5. Beta-cyclodextrin-appended giant amphiphile: aggregation to vesicle polymersomes and immobilisation of enzymes.

    PubMed

    Felici, Marco; Marzá-Pérez, María; Hatzakis, Nikos S; Nolte, Roeland J M; Feiters, Martin C

    2008-01-01

    A giant amphiphile consisting of polystyrene end-capped with permethylated beta-cyclodextrin was synthesised and found to form vesicular structures when injected as a solution in THF into water. The ability of the cyclodextrins on the surface of the polymersomes to form inclusion complexes with hydrophobic compounds was tested by carrying out a competition experiment with a fluorescent probe sensitive to the polarity of the surrounding medium. It was found that 1-adamantol can displace the fluorescent probe from the cavities of the cyclodextrin moieties of the polymersomes. The recognition of molecules by cell membranes in nature is often based on interactions with specific membrane receptors. To mimic this behaviour, the enzyme horseradish peroxidase was modified with adamantane groups through a poly(ethylene glycol) spacer and its interaction with the polymersomes was investigated. It was established that the presence of adamantane moieties on each enzyme allowed a host-guest interaction with the multifunctional surface of the polymersomes. PMID:18810732

  6. Thermodynamic analysis of the binding of a hepatoprotectant drug, thioctic acid, by beta-cyclodextrin.

    PubMed

    Junquera, E; Aicart, E

    1999-06-01

    Spectroscopic and thermodynamic studies of the binding of a hepatoprotectant drug, thioctic acid, by beta-cyclodextrin (beta-CD) have been carried out using UV-vis and pH potentiometric measurements. The UV-vis spectra and the pH of the aqueous solutions of the drug were measured (i) as a function of total drug concentration in the absence of cyclodextrin, and (ii) as a function of cyclodextrin concentration at constant drug concentration. The spectroscopic study was done at pH = 7 and 25 degrees C, while the potentiometric study was performed at several temperatures ranging from 15 to 40 degrees C. From the spectroscopic data, the molar absorption coefficient, epsilon, for the pure drug in aqueous media and the stoichiometry of the inclusion complex with beta-CD were determined. The dissociation constant, Ka, of the pure drug (which is a weak acid), and the association constants of the complexes formed by beta-cyclodextrin and both the nonionized (HTIO) and ionized (TIO-) forms of the drug, have been simultaneously determined at several temperatures from the pH data, without the necessity of working with buffered solutions. The nonionic forms are complexed by the beta-CD with higher affinity than their ionic counterparts. From the dependency of the association constants on temperature (van't Hoff analysis), the inclusion complexes formed by HTIO or TIO- and the beta-CD were found to be enthalpy driven, with a favorable enthalpic term dominant over an unfavorable entropic term. Both contributions were found to show a possible dependence with temperature (DeltaCpo not equal 0). This pattern may reveal the contribution of van der Waals interactions, hydrophobic effect, and solvent reorganization as the main driving forces promoting the complexation. PMID:10350499

  7. Inclusion complexation of pinostrobin with various cyclodextrin derivatives.

    PubMed

    Kicuntod, Jintawee; Khuntawee, Wasinee; Wolschann, Peter; Pongsawasdi, Piamsook; Chavasiri, Warinthorn; Kungwan, Nawee; Rungrotmongkol, Thanyada

    2016-01-01

    Pinostrobin (PNS) is one of the important flavonoids and can be abundantly found in the rhizomes of fingerroot (Boesenbergia rotrunda) and galangal (Alpinia galangal and Alpinia officinarum), the herbal basis of Southeast Asian cooking. Similar to other flavonoids, PNS exhibits anti-oxidative, anti-inflammatory and anti-cancer properties. However, this compound has an extremely low water solubility that limits its use in pharmaceutical applications. Beta-cyclodextrin (βCD) and its derivatives, 2,6-dimethyl-βCD (2,6-DMβCD) and the three hydroxypropyl-βCDs (2-HPβCD, 6-HPβCD and 2,6-DHPβCD), have unique properties that enhance the stability and solubility of such low-soluble guest molecules. In the present study, molecular dynamics simulations were applied to investigate the dynamics and stability of PNS inclusion complexes with βCD and its derivatives (2,6-DMβCD, 2,6-DHPβCD, 2-HPβCD and 6-HPβCD). PNS was able to form complexes with βCD and all four of its derivatives by either the chromone (C-PNS) or phenyl (P-PNS) ring dipping toward the cavity. According to the molecular mechanics-generalized Born surface area binding free energy values, the stability of the different PNS/βCD complexes was ranked as 2,6-DHPβCD>2,6-DMβCD>2-HPβCD>6-HPβCD>βCD. These theoretical results were in good agreement with the stability constants that had been determined by the solubility method. PMID:26709752

  8. In vitro and in vivo evaluation of oral tablet formulations prepared with ketoconazole and hydroxypropyl-beta-cyclodextrin.

    PubMed

    Taneri, Filiz; Ozcan, Ipek; Guneri, Tamer

    2010-04-01

    The objective of this study was to enhance the solubility, dissolution rate, and oral bioavailability of a very poorly water-soluble anti-fungal agent, ketoconazole (KET), by inclusion complexation with a highly-soluble cyclodextrin derivative, hydroxypropyl-beta cyclodextrin (HP-beta-CD). Two groups of tablets containing KET alone and KET:HP-beta-CD (1:2) kneaded product (KP) including magnesium stearate and lactopress (anhydrous and spray-dried) as excipients were prepared by direct compression method. After the characterization studies, the in vitro dissolution studies of these tablets in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were carried out. To evaluate the in vivo bioavailability, the tablets were administered orally to rabbits and drug levels in serum were determined by HPLC. Tablets containing the cyclodextrin complex showed a higher in vitro dissolution rate and bioavailability compared to the tablets containing KET alone. PMID:20148713

  9. Inclusion of terpenes in cyclodextrins: Preparation, characterization and pharmacological approaches.

    PubMed

    Lima, Pollyana S S; Lucchese, Angélica M; Araújo-Filho, Heitor G; Menezes, Paula P; Araújo, Adriano A S; Quintans-Júnior, Lucindo J; Quintans, Jullyana S S

    2016-10-20

    Terpenes constitute the largest class of natural products and are important resources for the pharmaceutical, food and cosmetics industries. However, due to their low water solubility and poor bioavailability there has been a search for compounds that could improve their physicochemical properties. Cyclodextrins (natural and derived) have been proposed for this role and have been complexed with different types of terpenes. This complexation has been demonstrated by using analytical techniques for characterizing complexes such as DSC, NMR, XRD, FTIR, and TGA. The formation of inclusion complexes has been able to improve drug characteristics such as bioavailability, solubility and stability; and to enhance biological activity and efficacy. This review shows strong experimental evidence that cyclodextrins improve the pharmacological properties of terpenes, and therefore need to be recognized as being possible targets for clinical use. PMID:27474645

  10. Electrospinning of functional poly(methyl methacrylate) nanofibers containing cyclodextrin-menthol inclusion complexes.

    PubMed

    Uyar, Tamer; Nur, Yusuf; Hacaloglu, Jale; Besenbacher, Flemming

    2009-03-25

    Electrospinning of nanofibers with cyclodextrin inclusion complexes (CD-ICs) is particularly attractive since distinct properties can be obtained by combining the nanofibers with specific functions of the CD-ICs. Here we report on the electrospinning of poly(methyl methacrylate) (PMMA) nanofibers containing cyclodextrin-menthol inclusion complexes (CD-menthol-ICs). These CD-menthol-IC functionalized nanofibers were developed with the purpose of producing functional nanofibers that contain fragrances/flavors with high temperature stability, and menthol was used as a model fragrance/flavor material. The PMMA nanofibers were electrospun with CD-menthol-ICs using three type of CD: alpha-CD, beta-CD, and gamma-CD. Direct pyrolysis mass spectrometry (DP-MS) studies showed that the thermal evaporation of menthol occurred over a very high and a broad temperature range (100-355 degrees C) for PMMA/CDmenthol-IC nanowebs, demonstrating the complexation of menthol with the CD cavity and its high temperature stability. Furthermore, as the size of CD cavity increased in the order alpha-CD<beta-CDbeta-CD>alpha-CD. PMID:19420480

  11. TDDFT study of UV-vis spectra of permethrin, cypermethrin and their beta-cyclodextrin inclusion complexes: A comparison of dispersion correction DFT (DFT-D3) and DFT

    NASA Astrophysics Data System (ADS)

    Chen, Feifei; Wang, Yujiao; Xie, Xiaomei; Chen, Meng; Li, Wei

    2014-07-01

    A comparative study of DFT and DFT-D3 has been carried out on the UV-vis absorption of permethrin, cypermethrin and their β-cyclodextrin inclusion complexes. The TDDFT method with PCM (or COSMO) model was adopted and B3LYP, BLYP and BLYP-D3 functionals were selected. Comparing the simulated spectra with experimental one, we can notice that pure BLYP functional can better reproduce the UV-vis spectra than hybrid B3LYP, but empirical dispersion corrections BLYP-D3 has better performance than BLYP. BLYP-D3 calculations reveal that the main absorption bands of permethrin and cypermethrin arise from the π → π* transition, after encapsulated by β-CD to form inclusion complexes, the host-guest intermolecular charge transfer (ICT) makes the main absorption bands to be changed significantly in wavelength and intensity.

  12. Complexation with beta-cyclodextrin confers oral activity on the flavonoid dioclein.

    PubMed

    Rezende, Bruno A; Cortes, Steyner F; De Sousa, Frederico B; Lula, Ivana S; Schmitt, Martine; Sinisterra, Rubén D; Lemos, Virginia S

    2009-02-01

    Dioclein is a flavonoid reported to have many beneficial effects on the cardiovascular system such as vasorelaxant, hypotensive, antioxidant and antiarrythmogenic activities. However, use as pharmaceuticals is limited due to the lack of oral activity and low water solubility. In this work, intending to improve its oral activity, we performed a 1:1 inclusion complex (IC) between dioclein and beta-cyclodextrin (beta-CD). The IC was characterized by nuclear magnetic resonance and infrared spectroscopy and its vasodilator and hypotensive effects were evaluated in mice. The inclusion of dioclein in beta-CD increased the water solubility 44% compared to free dioclein. The IC (2.5mgkg(-1)) produced a higher and long lasting change in systolic blood pressure (SBP) after intraperitoneal administration compared to free dioclein. When given orally, free dioclein (10mgkg(-1)) showed no hypotensive effect while the IC induced a pronounced decrease in SBP. The in vitro vasodilator effect of dioclein was unchanged by its inclusion in beta-CD showing that the IC does not change the interaction between dioclein and its cellular targets. In conclusion, our results show that the new complex prepared by inclusion of dioclein in beta-CD improves the hypotensive effect of the flavonoid by increasing its bioavailability and enables dioclein to be effective after oral administration. The mechanism underling the increase in bioavailability is probably a consequence of a protective effect of beta-CD against in vivo biodegradation by enzymes and possibly increased water solubility. PMID:18955122

  13. Modified β-Cyclodextrin Inclusion Complex to Improve the Physicochemical Properties of Albendazole. Complete In Vitro Evaluation and Characterization

    PubMed Central

    García, Agustina; Leonardi, Darío; Salazar, Mario Oscar; Lamas, María Celina

    2014-01-01

    The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms. PMID:24551084

  14. Modified β-cyclodextrin inclusion complex to improve the physicochemical properties of albendazole. complete in vitro evaluation and characterization.

    PubMed

    García, Agustina; Leonardi, Darío; Salazar, Mario Oscar; Lamas, María Celina

    2014-01-01

    The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms. PMID:24551084

  15. Quercetin/beta-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture.

    PubMed

    Borghetti, Greice S; Lula, Ivana S; Sinisterra, Ruben D; Bassani, Valquiria L

    2009-01-01

    The present study was designed to investigate the influence of operating conditions (temperature, stirring time, and excess amount of quercetin) on the complexation of quercetin with beta-cyclodextrin using a 2(3) factorial design. The highest aqueous solubility of quercetin was reached under the conditions 37 degrees C/24 h/6 mM of quercetin. The stoichiometric ratio (1:1) and the apparent stability constant (Ks = 230 M(-1)) of the quercetin/beta-cyclodextrin complex were determined using phase-solubility diagrams. The semi-industrial production of a 1:1 quercetin/beta-cyclodextrin solid complex was carried out in aqueous solution followed by spray-drying. Although the yield of the spray-drying process was adequate (77%), the solid complex presented low concentration of quercetin (0.14%, w/w) and, thus, low complexation efficiency. The enhancement of aqueous solubility of quercetin using this method was limited to 4.6-fold in the presence of 15 mM of beta-cyclodextrin. Subsequently, an inclusion complex was prepared via physical mixture of quercetin with beta-cyclodextrin (molar ratio of 1:1 and quercetin concentration of 23% (w/w)) and characterized using infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, and scanning electron microscopy analyses. The enhancement of aqueous solubility of quercetin using this method was 2.2-fold, similar to that found in the complex prepared in aqueous solution before the spray-drying process (2.5-fold at a molar ratio of 1:1, i.e., 6 mM of quercetin and 6 mM of beta-cyclodextrin). PMID:19280349

  16. Encapsulation in lipospheres of the complex between butyl methoxydibenzoylmethane and hydroxypropyl-beta-cyclodextrin.

    PubMed

    Scalia, Santo; Tursilli, Rosanna; Sala, Nicoletta; Iannuccelli, Valentina

    2006-08-31

    The aim of this study was to investigate the incorporation into lipospheres of the complex between hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and the sunscreen agent, butyl methoxydibenzoylmethane (BMDBM) and to examine the influence of this system on the sunscreen photostability. The formation of the inclusion complex was confirmed by thermal analysis and powder X-ray diffraction. Lipid microparticles loaded with free BMDBM or its complex with HP-beta-CD were prepared using tristearin as the lipid material and hydrogenated phosphatidylcholine as the emulsifier. The obtained lipospheres were characterized by scanning electron microscopy and differential scanning calorimetry. The microparticle size (15-40 microm) was not affected by the presence of the complex. Release of BMDBM from the lipospheres was lower when it was incorporated as inclusion complex rather than as free molecule. Unencapsulated BMDBM, its complex with HP-beta-CD, the sunscreen-loaded lipospheres or the lipoparticles containing the BMDBM/HP-beta-CD complex, were introduced into a model cream (oil-in-water emulsion) and irradiated with a solar simulator. The photodegradation studies showed that all the examined systems achieved a significant reduction of the light-induced decomposition of the free sunscreen agent (the BMDBM loss decreased from 28.9 to 17.3-15.2%). However, photolysis experiments performed during 3 months storage of the formulations, demonstrated that the photoprotective properties of the HP-beta-CD complex and of BMDBM alone-loaded lipospheres decreased over time, whereas the microencapsulated HP-beta-CD/BMDBM complex retained its photostabilization efficacy. Therefore, incorporation in lipid microparticles of BMDBM in the cyclodextrin complex form is more effective in enhancing the sunscreen photostability than the complex alone or the liposphere-entrapped free BMDBM. PMID:16713145

  17. Optical enrichment of dansyl-rac-amino acids by formation of crystalline inclusion complexes with cyclodextrins.

    PubMed

    Jin, H L; Stalcup, A; Armstrong, D W

    1989-01-01

    Optical enrichment from racemic dansyl-leucine, dansyl-norleucine, and dansyl-phenylalanine with both beta- and gamma-cyclodextrins in water is reported. Initial crystallization yielded the dansyl-L-Leucine isomer complexed in excess with beta-cyclodextrin with an optical purity of 62-78% depending on experimental conditions. The optical purities obtained for L-norleucine and L-phenylalanine were 71 and 64%, respectively. The optical purity can be increased with continued recrystallization. The dansyl-D-leucine isomer was obtained in the mother liquor with an optical purity of 54-93% depending on experimental conditions. The optical purities obtained for D-norleucine and D-phenylalanine were 72 and 58%. The optical purity of the isomer depended on the molar ratio of host:guest and the pH value of the solution. Optimum enrichment of both enantiomers was achieved with host:guest ratios of 2:1 and 3:1. Although maximum crystalline yield of the dansyl-leucine/CD inclusion complex was obtained at a pH of 3.5, optical purity of both enantiomers was less than that obtained at other pHs. The influence of the molar ratio of host:guest and the pH value of the solution are discussed. This method is suitable for large-scale enantiomeric separations. PMID:2642042

  18. Influence of beta-cyclodextrin and chitosan in the formulation of a colon-specific drug delivery system.

    PubMed

    Rehman, K; Amin, M C I M; Muda, S

    2013-12-01

    The increase in diseases of the colon underscores the need to develop cost-effective site-directed therapies. We formulated a polysaccharide-based matrix system that could release ibuprofen under conditions simulating those in the colon by employing a wet granulation method. Tablets were prepared in a series of formulations containing a polysaccharide (beta-cyclodextrin and chitosan) matrix system along with ethylcellulose. We characterized physicochemical properties and performed an in vitro drug release assay in the absence and presence of digestive enzymes to assess the ability of the polysaccharides to function as a protective barrier against the upper gastrointestinal environment. Fourier transform infrared spectroscopy studies revealed no chemical interaction between ibuprofen and polysaccharides; however, spectrum analysis suggested the formation of an inclusion complex of beta-cyclodextrin with ibuprofen. The formulations contained 50% ethylcellulose and 50% beta-cyclodextrins (1:1) were proven to be the better formulation that slowly released the drug until 24 h (101.04 ± 0.65% maximum drug release in which 83.08 ± 0.89% drug was released in colonic medium) showed better drug release profiles than the formulations containing chitosan. We conclude that a beta-cyclodextrin drug carrier system may represent an effective approach for treatment of diseases of the colon. PMID:23842943

  19. Antipyrine-gamma cyclodextrin inclusion complex: Molecular modeling, preparation, characterization and cytotoxicity studies

    NASA Astrophysics Data System (ADS)

    Gannimani, Ramesh; Perumal, Amanda; Ramesh, Muthusamy; Pillay, Karen; Soliman, Mahmoud E.; Govender, Patrick

    2015-06-01

    Molecular docking, semi-empirical and molecular dynamics studies were conducted for α, β and γ-cyclodextrin-associated inclusion complexes of antipyrine. The results of molecular modeling were systematically analyzed to determine the stability of inclusion complexes. In preliminary computational screening, β and γ-cyclodextrin inclusion complexes of antipyrine were found to be more stable as compared to α-cyclodextrin based on docking score and binding free energies. Further, inclusion complex of antipyrine with γ-cyclodextrin was prepared by freeze drying method. Formation of the inclusion complex was investigated by solid state characterization techniques such as thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy. The changes observed in decomposition temperature, diffractogram, vibrational frequencies and morphological appearance confirmed the formation of inclusion complex. In addition, results from 1H NMR and 2D NOESY studies supported the inclusion phenomenon. The results obtained from computational studies were found to be in consistent with experimental data to ascertain the encapsulation of antipyrine into γ-cyclodextrin. The inclusion complex was found to be non-toxic toward MDCK-1 cell lines. Thus, this approach may be helpful in the formulation of drug molecules using cyclodextrins.

  20. Probing inclusion complexes of cyclodextrins with amino acids by physicochemical approach.

    PubMed

    Roy, Mahendra Nath; Roy, Aditi; Saha, Subhadeep

    2016-10-20

    Formations of host-guest inclusion complexes of two natural amino acids, viz., l-Leucine and l-Isoleucine as guests with α and β-cyclodextrins have been investigated which include diverse applications in modern science such as controlled delivery in the field of pharmaceuticals, food processing etc. Surface tension and conductivity studies establish the formation of inclusion complexes with 1:1 stoichiometry. The interactions of cyclodextrins with amino acids have been supported by density, viscosity, refractive index, hydration and solvation number measurements indicating higher degree of inclusion in case of α-cyclodextrin. l-Leucine interacts more with the hydrophobic cavity of cyclodextrin than its isomer. With the help of stability constant by NMR titration, hydrophobic effect, H-bonds and structural effects the formations of inclusion complexes have been explained. PMID:27474589

  1. Preparation and physicochemical characterization of amoxicillin beta-cyclodextrin complexes.

    PubMed

    Bisson-Boutelliez, Catherine; Fontanay, Stephane; Finance, Chantal; Kedzierewicz, Francine

    2010-06-01

    Amoxicillin (AMOX), a penicillin A, belongs to the beta-lactam family It is usually the drug of choice within the class because it is better absorbed, following oral administration, than other beta-lactam antibiotics. Its beta-lactamase degradation might be prevented by using a molecular [AMOX:beta-CD] complex. The aim of this work was to prepare complexes using two methods and then characterize interactions between AMOX and the native beta-CD. The extent of complexation in solution has been evaluated by high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), and 2D rotating-frame Overhauser enhancement spectroscopy (2D ROESY). Mass changes (TG), calorimetric effects (DSC), and mass spectrometry (MS) were determined on the same sample under identical conditions using the Skimmer coupling system. Skimmer and infrared spectroscopy (FT-IR) were used to characterize the solid state of the binary system. Complexation of AMOX with beta-CD was proven by FT-IR, NMR, DSC, and HPLC. The 2D ROESY spectra did not show any dipolar proton interaction of the AMOX with cyclodextrin. The 1:1 stoichiometry of the complex was obtained by HPLC. The stability constant for AMOX with beta-CD was determined to be 1,878 M(-1). In the [AMOX:beta-CD] complex, the phenyl group is included inside the beta-CD, and the ionized carboxyl group on the penam ring forms hydrogen bonds with the secondary hydroxyl groups of another beta-CD to keep the complex stable. Preparation methods allowed exactly the same complex. PMID:20352533

  2. Enhancement of specific biological activity of dipyridamole by complexation with beta-cyclodextrin.

    PubMed

    Fregnan, G B; Bertè, F

    1990-01-01

    Dipyridamole forms an inclusion complex with beta-cyclodextrin (dip-beta-CD) which shows better solubility and bioavailability than the uncomplexed compound. The present studies have demonstrated that dip-beta-CD is more effective than dipyridamole either as base or HCl (dispersed or not in lactose) on some important cardiovascular parameters when orally administered to conscious animals. In particular, dip-beta-CD causes a stronger and prompter coronary and carotid vasodilatation in dogs, at doses which weakly influence the systemic arterial pressure and the heart rate. In addition, platelets collected from treated rabbits at various intervals appear to be protected from sodium adenosine diphosphate-induced aggregation in vitro more effectively and rapidly by dip-beta-CD than by dipyridamole. Studies on tail bleeding time have confirmed that dip-beta-CD is more active than dipyridamole when given orally to mice. These biological findings are fully in agreement with other oral bioavailability studies in dogs and men indicating that dip-beta-CD gives quicker and higher blood levels with smaller interindividual variability than dipyridamole. PMID:2345776

  3. Supramolecular complex of fluoxetine with beta-cyclodextrin: an experimental and theoretical study.

    PubMed

    de Sousa, Frederico B; Denadai, Angelo M Leite; Lula, Ivana S; Lopes, Juliana F; Dos Santos, Hélio F; De Almeida, Wagner B; Sinisterra, Rubén D

    2008-04-01

    In this work the complex formed between beta-cyclodextrin (betaCD) and fluoxetine (FLU) was investigated by experimental and computational methods. From Horizontal Attenuated Total Reflectance (HATR) was possible to verify a strong modification in the vibrational modes of betaCD and FLU, indicating interactions between them. The Nuclear Magnetic Resonance (NMR) experiments confirm these interactions through the change in chemical shifts in (1)H spectra, reduction in longitudinal relaxation times values, and the Nuclear Ouverhauser Effect confirm the inclusion of aromatic rings of FLU into the betaCD. The structures of the proposed inclusion compounds were optimized at PM3 semiempirical level of theory. In addition, single point calculations at the Density Functional Theory (DFT) level, using the Becke, Lee, Yang, and Parr functional and 6-31G(d,p) basis set, were used to determine the interaction energy for these structures. The DFT calculations identified the aromatic ring, which contains the CF(3) group as the most stable into the betaCD by an amount of, 11.7 kcal mol(-1), in the gas phase. Polarized continuum model, at the DFT level mentioned, was used to investigate the solvent effect, and the results corroborated the gas phase analysis. A high equilibrium constant (K approximately 6921+/-316) and the stoichiometry, 1:1, were obtained by Isothermal Titration Calorimetry (ITC) experiments. PMID:18255241

  4. 2-Hydroxypropyl-beta-cyclodextrin extracts 2-phenylphenol from silicone tubing.

    PubMed

    den Brok, Monique W J; van der Schoot, Sabien C; Nuijen, Bastiaan; Hillebrand, Michel J X; Beijnen, Jos H

    2004-07-01

    Cyclodextrins are capable to solubilise lipophilic drugs via (partial) inclusion in their lipophilic cavity. This, however, also provides the potential for the extraction of small molecules from production materials. In the present study, the potency of the commercially available and used cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) to extract the preservative 2-phenylphenol (2-PP) from platinum cured silicone tubing was tested. The presence of 2-PP was structurally confirmed with HPLC-UV and LC/MS/MS in HPbetaCD solutions after incubation with platinum cured silicone tubing. HPbetaCD concentration and prior tubing sterilisation were found not to influence the levels of 2-PP extracted. Interestingly, extraction to ethanol was 15-fold higher than observed for HPbetaCD solutions. 2-PP was extracted from silicone tubing during routine manufacture of a blank dosage form formulated with only HPbetaCD, resulting in detectable levels of 2-PP in the final product. In a freeze-dried dosage form containing HPbetaCD and an active pharmaceutical ingredient (exhibiting a stability constant for HPbetaCD/drug of 1045 L/mol), on the other hand, 2-PP was undetectable. PMID:15196635

  5. Biotreatment on cellulose fluff pulp: quaternary ammonium salts finish and grafting with beta-cyclodextrin.

    PubMed

    Ghemati, Djamila; Oudia, Atika; Aliouche, Djamel; Lamouri, Saad

    2009-11-01

    For its potential performances to be expanded, cellulose needs to be processed in different ways. Therefore, an object of the present work was to provide a chemical modification of cellulose through: a specific finish with two quaternary ammonium salts (namely Aliquat 336 and Aliquat 1529, respectively). Chemical grafting of beta-cyclodextrin derivative (beta-CD) onto fibers followed by the inclusion of benzoic acid in the grafted CD cavities as a probe chemical. Physicochemical properties and performances of the untreated and treated fibers have been determined with infrared spectra, microscopy, swelling measurements, antimicrobial finishing tests, and dye adsorption. Our results show that cellulose fibers can be efficiently modified with no significant changes in its structural and surface properties; the treated fibers show an attractive behavior in swelling, dye adsorption and antibacterial activity. PMID:19089647

  6. Study on vitamin K 3-cyclodextrin inclusion complex and analytical application

    NASA Astrophysics Data System (ADS)

    Zhenming, Dong; Xiuping, Liu; Guomei, Zhang; Shaomin, Shuang; Jinghao, Pan

    2003-07-01

    The inclusion interaction of the complexes between Vitamin K 3 (VK 3) and β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutylether-β-cyclodextrin (SBE-β-CD) were studied by using steady-state fluorescence measurements. The various factors affecting the inclusion process were examined in detail. The formation constants and inclusion stoichiometry for VK 3-CDs were determined. The results showed that the inclusion ability of β-CD and its derivatives was the order: SBE-β-CD>HP-β-CD>β-CD. The related inclusion mechanism is proposed to explain the inclusion process. A method of determining VK 3 was established with the linear range was 2.5×10 -6-5.0×10 -4 M, and was used to determine the VK 3 tablets. The recoveries were in the range of 97.52-103.5%. The results were satisfactory.

  7. Solubility Enhancement of Steviol Glycosides and Characterization of Their Inclusion Complexes with Gamma-Cyclodextrin

    PubMed Central

    Upreti, Mani; Strassburger, Ken; Chen, You L.; Wu, Shaoxiong; Prakash, Indra

    2011-01-01

    Steviol glycosidesrebaudioside (reb) A, C and D have low aqueous solubilities. To improve their aqueous solubilities, inclusion complex of steviol glycosides, reb A, C and D and gamma cyclodextrin were prepared by freeze drying method and further characterized by means of differential scanning calorimetry, Fourier transform infrared spectroscopy and Raman spectroscopy. The effect of gamma cyclodextrin on chemical shifts of the steviol glycosides was also studied in proton NMR experiments as well as in solid state 13C CP/MAS NMR experiments. These results indicated that the steviol glycosides were clearly in inclusion complex formation with the gamma cyclodextrin which also results in solubility enhancement of these steviol glycosides. Phase solubility studies showed that amounts of soluble reb A, C and D increased with increasing amounts of gamma cyclodextrin indicating formation of 1:1 stoichiometric and higher order inclusion complexes. PMID:22174615

  8. Ion-exclusion chromatography with conductimetric detection of aliphatic carboxylic acids on a weakly acidic cation-exchange resin by elution with benzoic acid-beta-cyclodextrin.

    PubMed

    Tanaka, Kazuhiko; Mori, Masanobu; Xu, Qun; Helaleh, Murad I H; Ikedo, Mikaru; Taoda, Hiroshi; Hu, Wenzhi; Hasebe, Kiyoshi; Fritz, James S; Haddad, Paul R

    2003-05-16

    In this study, an aqueous solution consisting of benzoic acid with low background conductivity and beta-cyclodextrin (beta-CD) of hydrophilic nature and the inclusion effect to benzoic acid were used as eluent for the ion-exclusion chromatographic separation of aliphatic carboxylic acids with different pKa values and hydrophobicity on a polymethacrylate-based weakly acidic cation-exchange resin in the H+ form. With increasing concentration of beta-cyclodextrin in the eluent, the retention times of the carboxylic acids decreased due to the increased hydrophilicity of the polymethacrylate-based cation-exchange resin surface from the adsorption of OH groups of beta-cyclodextrin. Moreover, the eluent background conductivity decreased with increasing concentration of beta-cyclodextrin in 1 mM benzoic acid, which could result in higher sensitivity for conductimetric detection. The ion-exclusion chromatographic separation of carboxylic acids with high resolution and sensitivity was accomplished successfully by elution with a 1 mM benzoic acid-10 mM cyclodextrin solution without chemical suppression. PMID:12830884

  9. Cyclodextrin inclusion compounds of vanadium complexes: structural characterization and catalytic sulfoxidation.

    PubMed

    Lippold, Ines; Vlay, Kristin; Görls, Helmar; Plass, Winfried

    2009-04-01

    Reaction of potassium vanadate with the hydrazone ligand derived from Schiff-base condensation of salicylaldehyde and biphenyl-4-carboxylic acid hydrazide (H(2)salhybiph) in the presence of two equivalents alpha-cyclodextrin (alpha-CD) in water yields the 1:2 inclusion compound K[VO(2)(salhybiph)@(alpha-CD)(2)]. Characterization in solution confirmed the integrity of the inclusion compound in the polar solvent water. The inclusion compound crystallizes together with additional water molecules as K[VO(2)(salhybiph)@(alpha-CD)(2)].18H(2)O in the monoclinic space group P2(1). Two alpha-CD rings forming a hydrogen bonded head to head dimer are hosting the hydrophobic biphenyl side chain of the complex K[VO(2)(salhybiph)]. The supramolecular aggregation of the inclusion compound in the solid state is established through hydrogen bonding interactions among adjacent alpha-CD hosts and with vanadate moieties of the guest complexes as well as ionic interactions with the potassium counterions. In contrast the supramolecular structure of the guest complex K[VO(2)(salhybiph)] without the presence of CD host molecules is governed by pi-pi-stacking interactions and additional CH/pi interactions. The new inclusion complex K[VO(2)(salhybiph)@(alpha-CD)(2)] and the analogous 1:1 inclusion compound with beta-CD were tested as catalyst in the oxidation of methyl phenyl sulfide (thioanisol) using hydrogen peroxide as oxidant in a water/ethanol mixture, under neutral as well as acidic conditions. PMID:19201031

  10. Synthesis, characterization and in vitro evaluation of dimethyl-beta-cyclodextrin-4-biphenylylacetic acid conjugate.

    PubMed

    Ventura, C A; Paolino, D; Pedotti, S; Pistarà, V; Corsaro, A; Puglisi, G

    2003-05-01

    Biphenylylacetic acid (BPAA) was linked to the free hydroxyl group of 2,6-di-O-methyl-beta-Cyclodextrin (DM-beta-CyD) through an ester linkage to obtain the site specific release of the drug to the colon. The conjugate at 1:1 mole ratio was separated from the reaction mixture by semipreparative reverse-phase HPLC and characterized by 1H-NMR, 13C-NMR, IR spectroscopy, mass spectrometry and elemental analysis. Chemico-physical characteristics, such as water solubility and dissolution rate, were evaluated comparatively to the BPAA-DM-beta-CyD inclusion complex. Hydrolysis rates were investigated in media simulating gastro-intestinal fluids and at pH 7.4 in the presence of porcine liver esterase. A rapid release of the drug was observed at acid pH value. In all cases a first order kinetic was observed, characterized by t1/2 value of 1.19, 19 and 4 h for chemical hydrolysis at pH 1.1, at pH 7.4 and enzymatic hydrolysis, respectively. In vitro permeation studies through caco-2 cells confirmed the ability of DM-beta-CyD to increase the absorption of included BPAA. A slow permeation was observed for the drug conjugate to DM-beta-CyD due to the slow release of BPAA. PMID:14578110

  11. In Vitro and In Vivo Evaluation of Oxatomide β-Cyclodextrin Inclusion Complex

    PubMed Central

    Hashem, Fahima M.; Mostafa, Mohamed; Shaker, Mahmoud; Nasr, Mohamed

    2013-01-01

    The objective of this study was to evaluate the influence of oxatomide β-cyclodextrin inclusion complex on the physicochemical properties and bioavailability of the drug. Oxatomide β-cyclodextrin solid complex was prepared with equimolar ratio of both oxatomide and β-cyclodextrin in presence or absence of water soluble polymers using different techniques. The coevaporated complex prepared in presence of PVP-K15 showed a prompt drug release and significantly increased % dissolution efficiency (P < 0.05) compared to the pure oxatomide. Moreover, the results of bioavailability evaluation of this complex in rabbits compared to commercial drug product indicated a 73.15% increase in the oral bioavailability of oxatomide. In conclusion, inclusion complex of oxatomide with β-cyclodextrin prepared by coevaporation in presence of PVP-K15 not only results in an enhancement of the oxatomide dissolution rate but also improves the bioavailability of oxatomide. PMID:26555988

  12. Vibrational properties of inclusion complexes: the case of indomethacin-cyclodextrin.

    PubMed

    Rossi, Barbara; Verrocchio, Paolo; Viliani, Gabriele; Scarduelli, Giorgina; Guella, Graziano; Mancini, Ines

    2006-07-28

    Vibrational properties of inclusion complexes with cyclodextrins are studied by means of Raman spectroscopy and numerical simulation. In particular, Raman spectra of the nonsteroidal, anti-inflammatory drug indomethacin undergo notable changes in the energy range between 1600 and 1700 cm(-1) when inclusion complexes with cyclodextrins are formed. By using both ab initio quantum chemical calculations and molecular dynamics, we studied how to relate such changes to the geometry of the inclusion process, disentangling single-molecule effects, from changes in the solid state structure or dimerization processes. PMID:16942160

  13. Synthesis of novel heterobranched beta-cyclodextrins having beta-D-N-acetylglucosaminyl-maltotriose on the side chain.

    PubMed

    Tanimoto, Toshiko; Omatsu, Mizue; Ikuta, Akiko; Nishi, Yuki; Murakami, Hiromi; Nakano, Hirofumi; Kitahata, Sumio

    2005-04-01

    From a mixture of N-acetylglucosaminyl-beta-cyclodextrin (GlcNAc-betaCD) and lactose, beta-D-galactosyl-GlcNAc-betaCD (Gal-GlcNAc-betaCD) was synthesized by the transfer action of beta-galactosidase. GlcNAc-maltotriose (Glc3) and Gal-GlcNAc-Glc3 were produced with hydrolysis of GlcNAc-betaCD by cyclodextrin glycosyltransferase, and Gal-GlcNAc-betaCD by bacterial saccharifying alpha-amylase respectively. Finally, GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3-betaCD were synthesized in 5.2% and 3.5% yield when Klebsiella pneumoniae pullulanase was incubated with the mixture of GlcNAc-Glc(3) and betaCD, or Gal-GlcNAc-Glc3 and betaCD respectively. The structures of GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3-betaCD were analyzed by FAB-MS and NMR spectroscopy and identified as 6-O-alpha-(6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD, and 6-O-alpha-(4-O-beta-D-galactopyranosyl-6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD respectively. PMID:15849411

  14. Neutron diffraction of alpha, beta and gamma cyclodextrins: Hydrogen bonding patterns

    SciTech Connect

    Hingerty, B.; Klar, B.; Hardgrove, G.L.; Betzel, C.; Saenger, W. )

    1984-08-01

    Cyclodextrins (CD's) have proved useful as model systems for the study of hydrogen bonding. They are torus-shaped molecules composed of six(alpha), seven(beta) or eight(gamma) (1----4) linked glucoses. Because of their particular geometry, they are able to act as a host to form inclusion complexes with guest molecules very much like enzymes. Cyclodextrins have been shown to exert catalytic activity on suitable included-substrate molecules; they catalyze the hydrolysis of phenylacetates, of organic pyrophosphates and of penicillin derivatives. They also accelerate aromatic chlorinations and diazo coupling by means of their primary and/or secondary hydroxyl groups, so that the rates of hydrolysis are enhanced by up to a factor of 400. In order to understand the hydrogen bonding in these enzyme models, neutron diffraction data were collected to unambiguously determine the hydrogen atom positions, which could not be done from the x-ray diffraction data. alpha-CD has been shown to have two different structures with well-defined hydrogen bonds, one tense and the other relaxed. An induced-fit-like mechanism for alpha-CD complex formation has been proposed. Circular hydrogen bond networks have also been found for alpha-CD due to the energetically favored cooperative effect. beta-CD with a disordered water structure possesses an unusual flip-flop hydrogen bonding system of the type O-H...H-O representing an equilibrium between two states: O-H...O in equilibrium O...H-O. gamma-CD with a disordered water structure similar to beta-CD also possesses the flip-flop hydrogen bond. This study demonstrates that hydrogen bonds are operative in disordered systems and display dynamics even in the solid state. 33 references.

  15. Use of Carboxymethyl-beta-cyclodextrin (CMCD) as Flushing Agent for Remediation of Metal Contaminated Soil

    NASA Astrophysics Data System (ADS)

    Skold, M. E.; Thyne, G. D.; McCray, J. E.; Drexler, J. W.

    2005-12-01

    One of the major challenges in remediating soil and ground water is the presence of mixed organic and inorganic contaminants. Due to their very different behavior, research has to a large extent focused on remediation of either organic or inorganic contaminants rather than mixed waste. Cyclodextrins (CDs) are a group of non-toxic sugar based molecules that do not sorb to soil particles and do not experience pore size exclusion. Thus, they have good hydraulic properties. CDs enhance the solubility of organic compounds by forming inclusion complexes between organic contaminants and the non-polar cavity at the center of the CD. By substituting functional groups to the cyclodextrin molecule it can form complexes with heavy metals. Previous studies have shown that carboxymethyl-beta-cyclodextrin (CMCD) can simultaneously complex organic and inorganic contaminants. The aim of this study is to compare how strongly CMCD complexes several common heavy metals, radioactive elements and a common divalent cation. Results from batch experiments show that CMCD has the ability to complex a wide array of heavy metals and radioactive elements. The solubility of metal oxalates and metal oxides clearly increased in the presence of CMCD. Logarithmic conditional formation constants ranged from 3.5 to 6 for heavy metals and from 3 to 6 for radioactive elements. Calcium, which may compete for binding sites, has a logarithmic conditional formation constant of 3.1. Batch experiments performed at 10 and 25 degrees C showed little temperature effect on conditional formation constants. Results from batch experiments were compared to results from column experiments where Pb was sorbed onto hydrous ferric oxide coated sand and subsequently removed by a CMCD solution. The results indicate that CMCD is a potential flushing agent for remediation of mixed waste sites.

  16. Ternary Inclusion Complexes of Rifaximin with β-Cyclodextrin and Sodium Deoxycholate for Solubility Enhancement.

    PubMed

    Kaur, Parminderjit; Rampal, Ankit; Singh Bedi, Preet M; Bedi, Neena

    2015-01-01

    Rifaximin is a rifamycin derivative, having extremely poor aqueous solubility. The objective of present study was to improve dissolution and solubility of drug using β-cyclodextrin inclusion complexes and also to evaluate the effect of presence of sodium deoxycholate on solubilization efficiency of β-cyclodextrin. The stochiometry of inclusion complexes of binary (drug-cyclodextrin) and ternary system (drug-cyclodextrin-sodium deoxycholate) were determined by phase solubility studies at 25 °C. The stability constants (K1:2) calculated from phase solubility analysis were 126 M(-1) and 267 M(-1) for binary and ternary systems respectively. The inclusion complexes were prepared by solvent evaporation method with the inclusion efficiency of 43% and 56.9% for binary and ternary systems followed by their characterization using fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry and in-vitro antibacterial activity. The solubility of drug was improved by 4.3 and 11.9 folds in binary and ternary inclusion complexes, respectively. Therefore, it can be concluded that the ternary inclusion complexation having better solubilization efficiency as compared to binary complexation. PMID:26279215

  17. Inclusion complexes of hydrochlorothiazide and β-cyclodextrin: Physicochemical characteristics, in vitro and in vivo studies.

    PubMed

    Mendes, Cassiana; Buttchevitz, Aline; Kruger, Jéssica H; Kratz, Jadel Müller; Simões, Cláudia Maria Oliveira; de Oliveira Benedet, Patricia; Oliveira, Paulo Renato; Silva, Marcos Antônio Segatto

    2016-02-15

    Hydrochlorothiazide is a thiazide diuretic widely used in clinics to treat arterial hypertension. It is a class IV drug according to the Biopharmaceutical Classification System, that is, it presents low solubility and low permeability and, consequently, low absorption in the gastrointestinal tract. As a strategy to improve stability and biopharmaceutical properties of hydrochlorothiazide, the use of cyclodextrins to produce inclusion complexes, applying different methods, was investigated. In the phase solubility studies, β-cyclodextrin was identified as the cyclodextrin which provided the most promising results in terms of the solubilization of the drug. The thermal analysis verified the interaction between hydrochlorothiazide and β-cyclodextrin, indicating the formation of inclusion complexes, and the thermal stability varied according to the preparation technique. The physicochemical characterization showed that in the inclusion complexes obtained by co-evaporation, kneading followed by freeze-drying and kneading followed by spray-drying the hydrochlorothiazide complexation mostly occurred with different degrees of amorphization and the drug solubility was improved. These three inclusion complexes presented better in vitro characteristics and the inclusion complex obtained by kneading followed by freeze-drying increased the in vivo diuretic activity of the drug accompanied by significant effects on natriuresis, kaliuresis and chloriuresis. The inclusion complex formation was effective in improving the biopharmaceutical properties of hydrochlorothiazide and protecting the drug from hydrolysis. This paper describes an important alternative approach to the development of liquid pharmaceutical formulations to pediatric administration, a real need of the current pharmaceutical market. PMID:26687444

  18. In vitro antiviral efficacy of the ganciclovir complexed with beta-cyclodextrin on human cytomegalovirus clinical strains.

    PubMed

    Nicolazzi, Céline; Venard, Véronique; Le Faou, Alain; Finance, Chantal

    2002-05-01

    The toxicity of the compounds currently used in the treatment of human cytomegalovirus (HCMV) infections in immunocompromised hosts may force the treatment to be discontinued. The aim of this study was to improve the antiviral activity of ganciclovir (GCV), one the most widely used drug, by complexing it with beta-cyclodextrin. Cyclodextrins (cds) have the property to form inclusion complexes with a great number of molecules and to enhance bioavailability and biological properties of these molecules. In this study, we investigated the in vitro antiviral activity of complexed GCV against several strains of HCMV: AD169, a reference strain, RCL-1, a laboratory mutant resistant to GCV, and four clinical isolates. The complexed GCV was more effective than free GCV against all HCMV strains tested. Cds as carriers for antiviral drugs would represent a useful adjunct to classical treatment procedures. They may make it possible to administer lower doses, thus reducing the toxic side effects of the drugs. PMID:12062397

  19. Exploration of inclusion complexes of neurotransmitters with β-cyclodextrin by physicochemical techniques

    NASA Astrophysics Data System (ADS)

    Roy, Mahendra Nath; Saha, Subhadeep; Kundu, Mitali; Saha, Binoy Chandra; Barman, Siti

    2016-07-01

    Molecular assemblies of β-cyclodextrin with few of the most important neurotransmitters, viz., dopamine hydrochloride, tyramine hydrochloride and (±)-epinephrine hydrochloride in aqueous medium have been explored by reliable spectroscopic and physicochemical techniques as potential drug delivery systems. Job plots confirm the 1:1 host-guest inclusion complexes, while surface tension and conductivity studies illustrate the inclusion process. The inclusion complexes were characterized by 1H NMR spectroscopy and association constants have been calculated by using Benesi-Hildebrand method. Thermodynamic parameters for the formation of inclusion complexes have been derived by van't Hoff equation, which demonstrate that the overall inclusion processes are thermodynamically favorable.

  20. Inclusion complexation between baicalein and β-cyclodextrin and the influence of β-cyclodextrin on the binding of baicalein with DNA: a spectroscopic approach.

    PubMed

    Sameena, Yousuf; Chandrasekaran, Sowrirajan; Israel V M V, Enoch

    2016-07-01

    This work deals with the commonly studied cyclic oligosaccharide and gains importance as it is entered on a drug delivering carbohydrate and provides insight into the oligosaccharide complex-biomolecular interaction. The binding of a flavone, baicalein, to β-cyclodextrin and calf thymus DNA is studied. The binding of baicalein to calf thymus DNA in the presence of β-cyclodextrin is analysed using the UV-vis absorption and fluorescence spectroscopy. The mode of binding and structure of the baicalein-β-cyclodextrin complex are reported. The role of the structure and the stoichiometry of the inclusion complex of baicalein-β-cyclodextrin in its influence on DNA binding are analysed. Highlights • This paper deals with the binding of a flavone, baicalein to β-cyclodextrin and/or DNA. • The inclusion complexation between baicalein and β-cyclodextrin is analysed. • The stoichiometry and the binding strength of the inclusion complex is reported. • The role of β-cyclodextrin in tuning the binding of baicalein to DNA is emphasized. • Spectroscopic and docking analysis are used to articulate the results. PMID:26308145

  1. Ionic self-assembled wormlike nanowires and their cyclodextrin inclusion-tuned transition.

    PubMed

    Li, Qiuhong; Chen, Xiao; Wang, Xudong; Zhao, Yurong; Ma, Fumin

    2010-08-19

    Wormlike nanowires have been successfully prepared via the ionic self-assembly (ISA) route from the cationic (ferrocenylmethyl)trimethylammonium iodide (FcMI) and the anionic sodium bis(2-ethyl-1-hexyl)sulfosuccinate (AOT). The formed FcM-AOT complexes have been proved to possess a composition of equal molar ratio and show good redox activity also due to the introduction of organic metal ferrocene. These complexes exhibit an ordered hexagonal columnar structure with the lattice spacing D of 2.49 nm. More interestingly, the wormlike nanowires interweave themselves together to form a net-like structure, and some of them are large enough to exhibit a high-order crystal structure. In addition, such an ISA organized aggregate can be changed into vesicles by including the Fc blocks into beta-cyclodextrins to form another supramolecular complex. The supramolecular structure and morphology of the vesicles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. Both the complex fabrication and transition mechanisms are discussed and found to be controlled by the inclusion equilibrium and the cooperative binding of noncovalent interactions, including the electrostatic interactions, pi-pi stacking, and amphiphilic hydrophobic association. PMID:20701373

  2. Oral bioavailability in sheep of albendazole from a suspension and from a solution containing hydroxypropyl-beta-cyclodextrin.

    PubMed

    Evrard, B; Chiap, P; DeTullio, P; Ghalmi, F; Piel, G; Van Hees, T; Crommen, J; Losson, B; Delattre, L

    2002-12-13

    Albendazole (ABZ) is a benzimidazole derivative with a broad spectrum of activity against human and animal helminthe parasites. ABZ has a very poor aqueous solubility. This study shows that hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is able to form inclusion complexes with ABZ and that is able to increase its aqueous solubility. A synergistic effect exists between HP-beta-CD and citric acid. The combination of HP-beta-CD (200 mM) and citric acid (50 mM) allows dissolution of more than 1.5 mg of ABZ per ml. The aim of this study is the in vivo evaluation in sheep of a solution of the inclusion complex of ABZ with HP-beta-CD in comparison with a suspension of the same drug. A significant (P<0.05) increase in the relative bioavailability is obtained with the solution containing the ABZ-HP-beta-CD complex as measured by ABZSO plasma levels. The area under the curve (AUC(0--> proportional, variant )) of the solution is 37% higher than that obtained with the suspension. Likewise the peak plasma concentration (C(max)) is twice that of the solution while the time to reach C(max) (T(max)) is reduced. PMID:12480310

  3. Water-soluble beta-cyclodextrins in paediatric oral solutions of spironolactone: preclinical evaluation of spironolactone bioavailability from solutions of beta-cyclodextrin derivatives in rats.

    PubMed

    Kaukonen, A M; Lennernäs, H; Mannermaa, J P

    1998-06-01

    Water-soluble derivatives of beta-cyclodextrin have been considered for solubilization of spironolactone in the formulation of a safe liquid preparation for premature infants. The oral absorption of spironolactone was studied in rats to evaluate the need to adjust spironolactone dosage in prospective clinical studies. Spironolactone was administered in solutions of sulphobutyl ether beta-cyclodextrin (SBE7) or dimethyl-beta-cyclodextrin (DM-beta-CyD) and also as spironolactone-containing powder papers (reference preparation). Spironolactone in SBE7 solution was administered intravenously to assess the extent of intestinal absorption from the different formulations. Spironolactone and the metabolites 7alpha-thiospirolactone, 7alpha-thiomethylspirolactone and canrenone were determined in rat serum after intravenous administration of spironolactone. Half-lives for spironolactone, 7alpha-thiomethylspirolactone and canrenone were 0.72 +/- 0.17, 1.5 +/- 0.3 and 2.2 +/- 0.3 h, respectively. Although, according to Cmax values, 7alpha-thiomethylspirolactone was the major serum metabolite in rats, higher AUC (area under the serum concentration-time curve) values were obtained for canrenone. After oral administration of spironolactone the bioavailabilities evaluated from the AUC values of 7alpha-thiomethylspirolactone were 27.5 +/- 9.3%, 81.3 +/- 28.8% and 82.8 +/- 28.6% for powder papers, DM-beta-CyD and SBE7 solutions, respectively. The oral absorption of spironolactone by rats was better after administration of spironolactone in SBE7 and DM-beta-CyD solutions than after administration as powder papers. Both cyclodextrin formulations enhanced spironolactone bioavailability to a similar extent despite some deacetylation of spironolactone in the presence of SBE7. A reduction of spironolactone dosage would be recommended during clinical studies with premature infants. These results indicate that SBE7 could be a safe and suitable excipient for the solubilization of

  4. Host-guest inclusion system of artesunate with β-cyclodextrin and its derivatives: Characterization and antitumor activity

    NASA Astrophysics Data System (ADS)

    Xie, Hudie; Yang, Bo; Wang, Fen; Zhao, Yulin

    2015-04-01

    Inclusion complexes between artesunate (ATS) and three cyclodextrins, namely β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD), were prepared by a suspension method. The complexes in both liquid and solid were characterized by phase-solubility diagram, nuclear magnetic resonance (NMR), powder X-ray diffraction (XRD) and thermoanalysis. The results suggested that artesunate was partly encapsulated within the cyclodextrin cavity to form a 1:1 stoichiometry host-guest compound. Especially in the SBE-β-CD complex, displayed the greatest stability constant. Significant enhancement of water solubility and thermal stability of ATS in present of β-CDs was shown. The calculated IC50 values indicated that the antitumor activities of inclusion complexes were better than that of ATS. Satisfactory aqueous solubility, along with high thermal stability of inclusion complexes will be potentially useful for their application on the formulation design of natural medicine.

  5. Dissolution Rate Enhancement, Design and Development of Buccal Drug Delivery of Darifenacin Hydroxypropyl β-Cyclodextrin Inclusion Complexes

    PubMed Central

    Jagdale, Swati C.; Mohanty, Prachyasuman; Chabukswar, Aniruddha R.; Kuchekar, Bhanudas S.

    2013-01-01

    Darifenacin is a urinary antispasmodic. The oral absorption of darifenacin is poor due to its low solubility and poor bioavailability (15–19%). Darifenacin was complexed with hydroxylropyl beta-cyclodextrin (Hpβ-CD). The best results were obtained with the coevaporation that interacts in a 1 : 1 drug : cyclodextrin molar ratio. The solid inclusion complexes were found to be amorphous in the characterization. The dissolution rate of darifenacin from the Hpβ-CD solid inclusion complex was increased compared to the powdered drug. The controlled release buccoadhesive patches for the delivery of darifenacin were prepared using HPMC K100M CR and HPMC K15. The coevaporation complex of the drug was used in the formulation due to its increased saturation solubility and increased ease of dissolution. The patches were evaluated for their surface pH, folding endurance, swelling, mucoadhesive properties, in vitro residence time, vapour transmission test, and in vitro and ex vivo release studies. Formulations Hb2 (2%) and Pb4 (4%) were found to be optimized. These two formulations can be used for buccal delivery of darifenacin which avoids first pass effect and leads to increased bioavailability of darifenacin. PMID:26556003

  6. Stretching a polymer brush by making in situ cyclodextrin inclusion complexes.

    PubMed

    Joseph, Julie; Dreiss, Cécile A; Cosgrove, Terence

    2008-09-16

    The interaction between poly(ethylene oxide) (PEO) chains grafted onto polystyrene latex particles and alpha-, beta-, and gamma-cyclodextrins (CD) was studied by small-angle neutron scattering. The particles were contrast-matched to the solvent in order that only the scattering from the polymer layers was detected. The signal from the layers was fitted to a double-exponential volume fraction profile. The effects of adding cyclodextrin on the polymer profile are shown as a function of cyclodextrin concentration. The polymer layers are seen to extend on addition of CD, which is consistent with a complexation between the grafted PEO and the CD molecules. The effect is the strongest with alpha-CD. PMID:18712892

  7. Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Herbicide Bentazon: Exploring Better Formulations

    PubMed Central

    Yáñez, Claudia; Cañete-Rosales, Paulina; Castillo, Juan Pablo; Catalán, Nicole; Undabeytia, Tomás; Morillo, Esmeralda

    2012-01-01

    The knowledge of the host-guest complexes using cyclodextrins (CDs) has prompted an increase in the development of new formulations. The capacity of these organic host structures of including guest within their hydrophobic cavities, improves physicochemical properties of the guest. In the case of pesticides, several inclusion complexes with cyclodextrins have been reported. However, in order to explore rationally new pesticide formulations, it is essential to know the effect of cyclodextrins on the properties of guest molecules. In this study, the inclusion complexes of bentazon (Btz) with native βCD and two derivatives, 2-hydroxypropyl-β-cyclodextrin (HPCD) and sulfobutylether-β-cyclodextrin (SBECD), were prepared by two methods: kneading and freeze-drying, and their characterization was investigated with different analytical techniques including Fourier transform infrared spectroscopy (FT-IR), differential thermal analysis (DTA), X-ray diffractometry (XRD) and differential pulse voltammetry (DPV). All these approaches indicate that Btz forms inclusion complexes with CDs in solution and in solid state, with a stoichiometry of 1∶1, although some of them are obtained in mixtures with free Btz. The calculated association constant of the Btz/HPCD complex by DPV was 244±19 M−1 being an intermediate value compared with those obtained with βCD and SBECD. The use of CDs significantly increases Btz photostability, and depending on the CDs, decreases the surface tension. The results indicated that bentazon forms inclusion complexes with CDs showing improved physicochemical properties compared to free bentazon indicating that CDs may serve as excipient in herbicide formulations. PMID:22952577

  8. Inclusion complexes of chlorzoxazone with β- and hydroxypropyl-β-cyclodextrin: Characterization, dissolution, and cytotoxicity.

    PubMed

    Tang, Peixiao; Li, Shanshan; Wang, Lili; Yang, Hongqin; Yan, Jin; Li, Hui

    2015-10-20

    This study aimed to improve the water solubility and reduce the toxicity of chlorzoxazone via complexation with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Inclusion complexes between chlorzoxazone and the two cyclodextrins (CDs) were prepared by freeze-drying method. Formation of the complexes was confirmed by FT-IR, PXRD, (1)H NMR, DSC, and SEM. The water solubility and dissolution rates of chlorzoxazone were significantly increased by complexation with the two CDs. Preliminary in vitro cytotoxicity tests showed that the complexes are less toxic to normal liver cells than free chlorzoxazone. In general, the HP-β-CD complex exhibited better dissolution properties than the β-CD complex in various dissolution media. Therefore, the HP-β-CD complex can be used to design novel formulations of chlorzoxazone. PMID:26256188

  9. A γ-cyclodextrin duplex connected with two disulfide bonds: synthesis, structure and inclusion complexes.

    PubMed

    Volkov, Sergey; Kumprecht, Lukáš; Buděšínský, Miloš; Lepšík, Martin; Dušek, Michal; Kraus, Tomáš

    2015-03-14

    Per(2,3,6-tri-O-benzyl)-γ-cyclodextrin was debenzylated by DIBAL-H to produce a mixture of C6(I),C6(IV) and C6(I),C6(V) isomeric diols, which were separated and isolated. The C2-symmetrical C6(I),C6(V) diol was transformed into dithiol and dimerized to produce a γ-cyclodextrin duplex structure. A crystal structure revealed tubular cavity whose peripheries are slightly elliptically distorted. The solvent accessible volume of the cavity of the γ-CD duplex is about 740 Å(3). Due to this large inner space the duplex forms very stable inclusion complexes with steroids; bile acids examined in this study show binding affinities to the γ-cyclodextrin duplex in the range of 5.3 × 10(7) M(-1)-1.9 × 10(8) M(-1). PMID:25616110

  10. Pickering emulsions with α-cyclodextrin inclusions: Structure and thermal stability.

    PubMed

    Diaz-Salmeron, Raul; Chaab, Ismail; Carn, Florent; Djabourov, Madeleine; Bouchemal, Kawthar

    2016-11-15

    This paper explores structural, interfacial and thermal properties of two types of Pickering emulsions containing α-cyclodextrin inclusion complexes: on one hand, emulsions were obtained between aqueous solutions of α-cyclodextrin and different oils (fatty acids, olive oil, silicone oil) and on the other hand, emulsions were obtained between these oils, water and micro or nano-platelet suspensions with inclusion complexes of hydrophobically-modified polysaccharides. The emulsions exhibit versatile properties according to the molecular architecture of the oils. Experiments were performed by microcalorimetry, X-ray diffraction and confocal microscopy. The aptitude of oil molecules to be threaded in α-cyclodextrin cavity is a determining parameter in emulsification and thermal stability. The heat flow traces and images showed dissolution, cooperative melting and de-threading of inclusion complexes which take place progressively, ending at high temperatures, close or above 100°C. Another important feature observed in the emulsions with micro-platelets is the partial substitution of the guest molecules occurring at room temperature at the oil/water interfaces without dissolution, possibly by a diffusion mechanism of the oil. Accordingly, the dissolution and the cooperative melting temperatures of the inclusion crystals changed, showing marked differences upon the type of guest molecules. The enthalpies of dissolution of crystals were measured and compared with soluble inclusions. PMID:27491001

  11. Rare 'head-to-tail' arrangement of guest molecules in the inclusion complexes of (+)- and (-)-menthol with β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Ceborska, Magdalena; Asztemborska, Monika; Lipkowski, Janusz

    2012-11-01

    The inclusion of (+)- and (-)-menthols in β-cyclodextrin has been studied by X-ray crystallography. The obtained [2:2] complexes show typical for β-cyclodextrin form of head-to-head dimer. In both (+)- and (-)-cases, the menthol molecule in one of cyclodextrins forming dimer exhibits disorder and occupies two major sites. Also both of the diastereoisomeric complexes show unusual 'head to tail' arrangement of guest molecules - two guest molecules are differently oriented inside β-cyclodextrin cavity. Stability constants for both complexes in solution were measured.

  12. Inclusion process of tetracycline in β and γ-cyclodextrins: A theoretical investigation

    NASA Astrophysics Data System (ADS)

    Costa, Mércia A. S.; Anconi, Cleber P. A.; Dos Santos, Hélio F.; De Almeida, Wagner B.; Nascimento, Clebio S.

    2015-04-01

    The present Letter reports results from a comprehensive theoretical analysis of the inclusion process involving the tetracycline (TC) by β and γ-cyclodextrin (CD). Structure and stabilization energies were calculated, both in gas phase and aqueous solution, using a sequential methodology based on semiempirical and density functional theory (DFT) calculations. By the results, a qualitative structure-property relationship could be established with two main structural features being relevant for inclusion complex stabilization: (i) the depth of inclusion, which favors the hydrophobic contact inside the cavity of CDs and (ii) the hydrogen bonds established between guest and host molecules.

  13. A DFT investigation on the host/guest inclusion process of prilocaine into β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    de Sousa, Sara Maria R.; Guimarães, Luciana; Ferrari, Jefferson L.; De Almeida, Wagner B.; Nascimento, Clebio S.

    2016-05-01

    A theoretical analysis of the host/guest inclusion process involving the prilocaine into the β-cyclodextrin was performed. Structure and stabilization energies were calculated, in both gas and aqueous phases, using Density Functional Theory level of theory. As results, a qualitative structure property relationship could be established with structural features being relevant for inclusion complex stabilization: (i) the hydrogen bonds established between guest and host molecules and (ii) the dispersion effect in the formation of the complexes. Besides, a theoretical 1H NMR analysis has shown to be an adequate procedure to predict correctly the inclusion mode of guest molecule into the host.

  14. Interaction of lead(II) with beta-cyclodextrin in alkaline solutions.

    PubMed

    Norkus, Eugenijus; Grinciene, Giedre; Vaitkus, Rimantas

    2002-10-01

    Polarographic and UV-spectrophotometric investigations of Pb(II) complex formation with beta-cyclodextrin have showed that the complexation of Pb(II) ions begins at pH >10. The formation of lead(II) 1:1 complex with the beta-cyclodextrin anion was observed at pH 10-11.5. The logarithm of the stability constant of this complex compound is 15.9+/-0.3 (20 degrees C, ionic strength 1.0), and the molar extinction coefficient value is ca. 5500 (lambda(max)=260 nm). With further increase in solution pH the Pb-beta-cyclodextrin complex decomposes and converts to Pb(OH)(2) or Pb(OH)(3)(-) hydroxy-complexes. This process occurs with a decrease in Pb(II) complexation degree. The latter result could be explained by a decrease in the beta-cyclodextrin anion activity. Neither Pb(OH)(2) nor Pb(OH)(3)(-) encapsulation into beta-CD cavity was observed. PMID:12423967

  15. Modulated dissolution rate from the inclusion complex of antichagasic benznidazole and cyclodextrin using hydrophilic polymer.

    PubMed

    Sá-Barreto, Lívia C L; Gustmann, Pricila C; Garcia, Felipe S; Maximiano, Flávia P; Novack, Kátia M; Cunha-Filho, Marcílio S S

    2013-01-01

    Benznidazole (BNZ) is the primary chemotherapeutic agent for treating Chagas' disease; however, its poor water solubility and irregular oral absorption lead to the treatment failure in the chronic phase. The aim of this work was to investigate the utility of the polymer hydroxypropyl methylcellulose (HPMC) in controlling the release of BNZ from solid inclusion complexes with cyclodextrin to overcome the problem of its bioavailability. Preliminary studies of solubility were conducted in solution using selected β-cyclodextrin derivatives according to an experimental mixture design. The best cyclodextrin composition was used to produce solid-state systems by kneading in the presence or absence of HPMC. The formulations were characterized by different physico-chemical techniques, including the dissolution rate. Hydroxypropyl-β-cyclodextrin (HPβCD) produced the greatest improvement in drug solubility and was selected for the development of solid systems. Assays confirmed the production of true inclusion complexes between BNZ and HPβCD. The dissolution rate of the BNZ-HPβCD system was markedly increased, while the presence of HPMC retarded drug release. An optimal formulation obtained by the combination of kneading systems developed in appropriate ratios could be a promising drug delivery system with a prolonged therapeutic effect coupled with more balanced bioavailability. The produced systems present interesting perspectives for Chagas' therapy. PMID:22200091

  16. Differential effects of modified beta-cyclodextrins on pharmacological activity and bioavailability of 4-biphenylacetic acid in rats after oral administration.

    PubMed

    Puglisi, G; Ventura, C A; Spadaro, A; Campana, G; Spampinato, S

    1995-02-01

    Gastric tolerability, absorption and pharmacological activity of the non-steroidal anti-inflammatory drug 4-biphenylacetic acid (BPAA), as an inclusion complex with beta-cyclodextrin (beta-CyD) or chemically modified beta-CyDs: 2,6-di-O-methyl-beta-CyD (DM-beta-CyD), 2,3,6-tri-O-methyl-beta-CyD (TM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD), were investigated in the rat after oral administration. BPAA absorption, determined from area under the plasma concentration-time curve (AUC), was increased by complexation with all beta-CyDs in the following order: DM-beta-CyD > TM-beta-CyD > HP-beta-CyD > beta-CyD. The carrageenan paw oedema test demonstrated a significant increase in anti-inflammatory activity of BPAA and the ED50 values, compared with BPAA alone, were reduced to about a third for the BPAA-DM-beta-CyD complex and halved for the others. BPAA complexed with DM-beta-CyD, HP-beta-CyD or beta-CyD showed better gastric tolerability compared with uncomplexed drug, whereas the BPAA-TM-beta-CyD complex produced marked gastric lesions similar in extent to BPAA alone. TM-beta-CyD (500 mg kg-1) and DM-beta-CyD (1000 mg kg-1) caused gastric erosions 21 h after oral administration. The pharmacokinetic profiles of BPAA-beta-CyD complexes have shown that DM-beta-CyD is the most effective in enhancing the bioavailability of BPAA. PMID:7602465

  17. Improved drug delivery properties of PVDF membranes functionalized with beta-cyclodextrin--application to guided tissue regeneration in periodontology.

    PubMed

    Boschin, F; Blanchemain, N; Bria, M; Delcourt-Debruyne, E; Morcellet, M; Hildebrand, H F; Martel, B

    2006-10-01

    The purpose of this study was to develop a membrane for guided tissue regeneration applicable in periodontology that could release antimicrobial agent during the healing period. Our strategy consisted to graft beta-cyclodextrin (beta-CD), a molecule that is known to form inclusion complexes with a large variety of drugs, onto PVDF membranes. Grafting occurred by using citric acid that provoked a crosslinking reaction of beta-CD, and the resulting polymer was imprisoned into the porous structure of the PVDF membrane. The reaction produced a weight increase of the membrane, the range of which depended on the temperature and on the time of curing applied in the process. The biological behavior of the membranes evaluated by proliferation and vitality tests showed good proliferation and improved activity of L132 epithelial cells on the raw and on the grafted membranes. Doxycyclin (DOX) and chlorhexidine (CHX) were used as antimicrobial agents. Their inclusion into the beta-CD cavity in aqueous solutions was confirmed by NMR spectroscopy. After the impregnation of the membranes with DOX and CHX, their release was studied in vitro in batch type experiments and measured by UV spectrophotometry. Low amounts of DOX and CHX were delivered from the raw membranes within the first few hours of tests. Grafted membranes, however, delivered DOX and CHX in larger quantities within 24 h and 10 days respectively. PMID:16758457

  18. Inclusion complexes of red bell pepper pigments with β-cyclodextrin: preparation, characterisation and application as natural colorant in yogurt.

    PubMed

    Gomes, Lidiane Martins Mendes; Petito, Nicolly; Costa, Valéria Gonçalves; Falcão, Deborah Quintanilha; de Lima Araújo, Kátia G

    2014-04-01

    This work aimed to prepare inclusion complexes between red bell pepper pigments and β-cyclodextrin using two different procedures (i.e., magnetic stirring and ultrasonic homogenisation), to characterise the prepared inclusion complexes and to evaluate the colour stability of a selected complex added to yogurt. The mass ratio of extract to β-cyclodextrin was 1:4. The formed extract: β-cyclodextrin complexes and a physical mixture of extract and β-cyclodextrin were evaluated by differential scanning calorimetry, Fourier transform-infrared spectroscopy, proton nuclear magnetic resonance, particle size distribution and Zeta potential. The obtained data showed that ultrasonic homogenisation resulted in better yield and inclusion efficiency compared to magnetic stirring. The yogurt with the added complex produced by ultrasonic homogenisation showed slower variations for the a(∗) (redness) and b(∗) (yellowness) indices compared to yogurt with added extract, indicating a higher protection of the colour during storage. PMID:24262579

  19. Characterization and evaluation of synthetic riluzole with β-cyclodextrin and 2,6-di-O-methyl-β-cyclodextrin inclusion complexes.

    PubMed

    Wang, Lili; Li, Shanshan; Tang, Peixiao; Yan, Jin; Xu, Kailin; Li, Hui

    2015-09-20

    β-Cyclodextrin (β-CD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD) inclusion complexes with riluzole (RLZ) were prepared to improve water solubility and broaden potential pharmaceutical applications. CDs/RLZ inclusion complexes were confirmed via phase solubility studies, FT-IR spectroscopy, PXRD, DSC, (1)H NMR, and SEM. Phase solubility studies indicated that β-CD and DM-β-CD can form 1:1 inclusion complexes with RLZ, and the stability constants were 663.17 and 1609.07M(-1), respectively. Water solubility and dissolution rate of RLZ were significantly improved in complex forms, implying that the inclusion complexes may develop pharmaceutical applications. Preliminary in vitro cytotoxicity assay also showed that RLZ hepatotoxicity was not increased in the inclusion complexes. PMID:26050882

  20. [Use of water-soluble beta-cyclodextrin derivatives as carriers of anti-inflammatory drug biphenylylacetic acid in rectal delivery].

    PubMed

    Arima, H; Kondo, T; Irie, T; Hirayama, F; Uekama, K; Miyaji, T; Inoue, Y

    1992-01-01

    To improve the rectal delivery of an anti-inflammatory drug, biphenylylacetic acid (BPAA), the use of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and heptakis (2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) was investigated. Inclusion complex formations of BPAA with both beta-CyDs in a molar ratio of 1:1 in water were ascertained, and their stability constants were determined. The dissolution of BPAA in water and the release of BPAA from an oleaginous suppository (Witepsol H-5) were significantly increased by beta-CyDs, depending on the magnitude of the stability constants of the water-soluble complexes. However, the serum levels of BPAA after rectal administration of the suppositories containing BPAA or its beta-CyDs complexes in rats increased in the order of BPAA alone much less than DM-beta-CyD less than or equal to HP-beta-CyD complex. The in situ recirculation study revealed that the greater the stability constant of the complex, the lesser was the absorption of BPAA from the rectal lumen of rats under the solution state. Both in vivo and in situ studies demonstrated that rather high amount of HP-beta-CyD (about 20% of dose) was absorbable from the rat's rectum, compared with DM-beta-CyD (less than 5% of dose), suggesting the possibility of the permeation of BPAA through the rectal membrane in the form of HP-beta-CyD complex. Furthermore, DM-beta-CyD and HP-beta-CyD significantly reduced the irritation of the rectal mucosa caused by BPAA after the administration of the suppositories to rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1578346

  1. Cyclodextrin inclusion complex of racecadotril: effect of drug-β- cyclodextrin ratio and the method of complexation.

    PubMed

    Semalty, Mona; Panchpuri, Mitali; Singh, Devendra; Semalty, Ajay

    2014-06-01

    Racecadotril is an antisecretory and antidiarrheal agent against watery diarrhoea in children. Racecadotril is a class II drug (as per Biopharmaceutical Classification System) with poor aqueous solubility and dissolution rate limited absorption. β-cyclodextrin complexation of solubility or dissolution rate limited drugs provides an amphiphilic complex with improved solubility and dissolution profile. Thus Racecadotril - β-cyclodextrin complex were prepared to improve its solubility and dissolution by imparting an environment of improved hydrophilicity. Racecadotril was complexed with β-cyclodextrin (in 1:1 and 1:2 molar ratios) by two different methods (solvent evaporation and kneading method). These inclusion complexes were evaluated for solubility, drug content, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X ray powder diffraction (XRPD) and in vitro dissolution study. The highest drug content (30.83%) was found in complex made by kneading method (RK1:1) in 1:1 molar ratio. Complex prepared by solvent evaporation method (RSE1:1, RSE1:2) were found to be showing irregular disc shaped non-porous surface, while the complexes prepared by kneading method (RK1:1, RK1:2) showed rough, fluffy, non-porous and irregular surface in SEM. Solubility of the drug improved up to 2 to 3 folds in the complexes. The complex RK1:1 showed the greatest improvement in solubility (from 28.98 to76.56 µg/ml). The dissolution of the complexes was also found to be improved. Complex prepared by solvent evaporation method in 1:1 molar ratio (RSE1:1) showed a marked improvement in percent drug release (100.33%) than that of pure drug (52.58%) at the end of 1 hour in dissolution study. FTIR, DSC and XRPD data confirmed the formation of inclusion complex. It was concluded that water solubility of all the complexes were increased when the drug was complexed with β-CD in 1:1 molar ratio. The complex made in 1:1 molar ratio (irrespective of the method) showed

  2. Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

    PubMed Central

    Trollope, Lee; Cruickshank, Dyanne L; Noonan, Terence; Bourne, Susan A; Sorrenti, Milena; Catenacci, Laura

    2014-01-01

    Summary The phytoalexin trans-resveratrol, 5-[(1E)-2-(4-hydroxyphenyl)ethenyl]-1,3-benzenediol, is a well-known, potent antioxidant having a variety of possible biomedical applications. However, its adverse physicochemical properties (low stability, poor aqueous solubility) limit such applications and its inclusion in cyclodextrins (CDs) has potential for addressing these shortcomings. Here, various methods of the attempted synthesis of inclusion complexes between trans-resveratrol and three methylated cyclodextrins (permethylated α-CD, permethylated β-CD and 2,6-dimethylated β-CD) are described. Isolation of the corresponding crystalline 1:1 inclusion compounds enabled their full structure determination by X-ray analysis for the first time, revealing a variety of guest inclusion modes and unique supramolecular crystal packing motifs. The three crystalline inclusion complexes were also fully characterized by thermal analysis (hot stage microscopy, thermogravimetric analysis and differential scanning calorimetry). To complement the solid-state data, phase-solubility studies were conducted using a series of CDs (native and variously derivatised) to establish their effect on the aqueous solubility of trans-resveratrol and to estimate association constants for complex formation. PMID:25670983

  3. Study on inclusion complex of cyclodextrin with methyl xanthine derivatives by fluorimetry

    NASA Astrophysics Data System (ADS)

    Wei, Yan-Li; Ding, Li-Hua; Dong, Chuan; Niu, Wei-Ping; Shuang, Shao-Min

    2003-10-01

    The inclusion complexes of β-cyclodextrin (β-CD) and HP-β-cyclodextrin (HP-β-CD) with caffeine, theophylline and theobromine were investigated by fluorimetry. Various factors affecting the formation of inclusion complexes were discussed in detail including forming time, pH effect and temperature. The results indicate that inclusion process was affected seriously by laying time and pH. The forming time of β-CD inclusion complexes is much longer than that of HP-β-CD. The optimum pH range is about 7-12 for caffeine, 8-10 for TP, 10.5-12 for TB. The intensities of their fluorescence increase with the decreasing of temperature. Their maximum excitation wavelengths are all in the range of 280-290 nm. The emission wavelength of caffeine and theophylline are both in the range of 340-360 nm, and that of theobromine is about 325 nm. The fluorescence signals are intensified with the increasing concentration of CD. The stoichiometry of the inclusion complexes of CD with these three methyl xanthine derivatives are all 1:1 and the formation constant are all calculated.

  4. Inclusion complexes of β-cyclodextrin-dinitrocompounds as UV absorber for ballpoint pen ink.

    PubMed

    Srinivasan, Krishnan; Radhakrishnan, S; Stalin, Thambusamy

    2014-08-14

    2,4-Dinitrophenol (2,4-DNP), 2,4-dinitroaniline (2,4-DNA), 2,6-dinitroaniline (2,6-DNA) and 2,6-dinitrobenzoic acid (2,6-DNB) has appeared for the UV absorption bands in different wavelength region below 400 nm, a combination of these dinitro aromatic compounds gave the broad absorption spectra within the UV region. The absorption intensities have been increased by preparation of the inclusion complex of dinitro compounds with β-cyclodextrin (β-CD). Prepared inclusion complexes are used to improve the UV protection properties of the ball point pen ink against photo degradation. The formation of solid inclusion complexes was characterized by FT-IR, and (1)H NMR spectroscopy. The UV protecting properties of these inclusion complexes were calculated their sun protection factor (SPF) is also discussed. The stability of the ballpoint pen ink has been confirmed by UV-Visible spectroscopic method. PMID:24813164

  5. Preparation and spectral investigation of inclusion complex of caffeic acid with hydroxypropyl-β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Zhang, Min; Li, Jinxia; Zhang, Liwei; Chao, Jianbin

    2009-01-01

    The inclusion complexation behavior of caffeic acid (CA) with hydroxypropyl-β-cyclodextrin (HP-β-CD) was studied by UV-vis, fluorescence spectroscopy and nuclear magnetic resonance spectroscopy (NMR). Experimental conditions including the concentration of HP-β-CD and media acidity were investigated in detail. The result suggested HP-β-CD was more suitable for including CA in acidity solution. The binding contants ( K) of the inclusion complexes were determined by linear regression analysis and the inclusion ratio was found to be 1:1. The water solubility of CA was increased by inclusion with HP-β-CD according to the phase-solubility diagram. The spatial configuration of complex has been proposed based on 1H NMR and two-dimensional (2D) NMR, the result suggested that CA was entrapped inside the hydrophobic core of HP-β-CD with the lipophilic aromatic ring and the portion of ethylene.

  6. Development of a myricetin/hydroxypropyl-β-cyclodextrin inclusion complex: preparation, characterization, and evaluation.

    PubMed

    Yao, Yashu; Xie, Yan; Hong, Chao; Li, Guowen; Shen, Hongyi; Ji, Guang

    2014-09-22

    Myricetin shows low oral bioavailability (<10%) in rats due to poor aqueous solubility, though it has various pharmacological activities. Complexation with cyclodextrins (CDs) is a potent pharmaceutical method to enhance the bioavailability of poorly soluble compounds. The myricetin/HP-β-CD inclusion complex was prepared and confirmed by DSC, PXRD, and SEM. Here, the inclusion mode is described in detail with regard to structural and energetic aspects using a phase solubility diagram and 1H NMR, NOESY, and FT-IR spectra. The water solubility and dissolution rate of myricetin were greatly enhanced by forming the myricetin/HP-β-CD inclusion complex. Consequently, the oral bioavailability of the myricetin/HP-β-CD inclusion complex in rats was effectively increased 9.4-fold over free myricetin, and its antioxidant activity was also improved. The present study provides useful information for the potential application of complexation with myricetin, a naturally occurring hydrophobic phenolic compound in herbal medicine. PMID:24906763

  7. Inclusion complexes of β-cyclodextrin-dinitrocompounds as UV absorber for ballpoint pen ink

    NASA Astrophysics Data System (ADS)

    Srinivasan, Krishnan; Radhakrishnan, S.; Stalin, Thambusamy

    2014-08-01

    2,4-Dinitrophenol (2,4-DNP), 2,4-dinitroaniline (2,4-DNA), 2,6-dinitroaniline (2,6-DNA) and 2,6-dinitrobenzoic acid (2,6-DNB) has appeared for the UV absorption bands in different wavelength region below 400 nm, a combination of these dinitro aromatic compounds gave the broad absorption spectra within the UV region. The absorption intensities have been increased by preparation of the inclusion complex of dinitro compounds with β-cyclodextrin (β-CD). Prepared inclusion complexes are used to improve the UV protection properties of the ball point pen ink against photo degradation. The formation of solid inclusion complexes was characterized by FT-IR, and 1H NMR spectroscopy. The UV protecting properties of these inclusion complexes were calculated their sun protection factor (SPF) is also discussed. The stability of the ballpoint pen ink has been confirmed by UV-Visible spectroscopic method.

  8. Electrospinning of Poly (epsilon-caprolactone) Fibers Functionalized with Cyclodextrins and their Inclusion Complexes

    NASA Astrophysics Data System (ADS)

    Narayanan, Ganesh

    Functionalization of polymeric nanofibers by cyclodextrins offers a novel way to enhance properties such as, small molecule encapsulation, efficient drug delivery, tissue engineering, improved mechanical and thermal behavior, in the resultant nanofibers. The advantage of using CDs, apart from their abundant availability from natural resources, biodegradability and biocompatibility, include their easy manipulation to obtain desired features in the nanofibers. In the first study, a unique way to electrospin PCL nanofibers with alpha- and gamma-CDs, without forming ICs was described. This was achieved by using a binary solvent mixture of chloroform/DMF, which is expected to hinder the formation of ICs. The resultant nanofibers were characterized by FTIR, DSC, TGA, SEM, water contact angle, and for the efficiency of PhP absorption. Based on the results, a simple model was proposed for both alpha- and gamma-CD filled PCL nanowebs. In the second study, electrospinning of PCL with beta-CD was performed from mixture of chloroform/DMF, and the nanofibers were characterized using FTIR, WAXD, TGA, and SEM. An interesting application of this material, i.e., as an absorbant for wound odors, was proposed, and subsequently the potential was studied by GC & XPS analysis. XPS indicated higher absorption of volatile fatty acids with higher CD loadings, whereas the absorption by the neat PCL nanofibers was little. The results found led to the suggestion that stabilizing CD over PCL by cross-linking will enhance the wound odor absorption potential, and this idea should be explored by further experimentation. In the third study, mechanically strong nanofibers were obtained from electrospinning PCL along with non-stochiometric inclusion complexes formed with PCL and alpha-CD, as a solution/suspension, from chloroform/DMF mixture. Non-stochiometric inclusion complexes were prepared from PCL and alpha-CD at various ratios, and were characterized by FTIR, DSC, and 1H-NMR. The electrospun

  9. Catalytic beta-cyclodextrin enzyme mimics as soman hydrolases

    SciTech Connect

    Seltzman, H.H.; Lonikar, M.S.

    1993-05-13

    The use of chemically accessible artificial enzymes as in vivo scavengers of soman offers an attractive approach for protecting the soldier from the debilitating and often fatal effects of this organophosphate poison. The ability of modified B-cyclodextrins to scavenge soman both in vitro and in vivo has been demonstrated. These enzyme mimics however are stoichiometric in their reaction, consuming and being consumed by one molecule of soman. The ability to inactivate multiple soman molecules, that is to function as a true catalytic enzyme, would further enhance scavenging by a factor that would be proportional to the turnover rate. We now report the synthesis and activity of a series of iodosobenzoic acid-B-cyclodextrin conjugates (IBA-BCD) that catalytically hydrolyzes soman. Two assays for enzyme like activity were conducted. The first for enhanced scavenging ability demonstrated that the IBA-BCD conjugates enhanced the scavenging of soman by nearly three orders of magnitude in a structure dependent manner compared to soman scavenging by BCD. The second assay, for catalytic activity, demonstrated that the tested compounds were able to scavenge a stoichiometric excess of soman (with turnover rates in the range of 5 to 13 mole soman/mole mimic/min). This is in contrast to stoichiometric scavengers, tested as controls, that were able to scavenge only one soman per cyclodextrin molecule.

  10. NMR spectroscopic characterization of β-cyclodextrin inclusion complex with vanillin

    NASA Astrophysics Data System (ADS)

    Pîrnau, Adrian; Bogdan, Mircea; Floare, Calin G.

    2009-08-01

    The inclusion of vanillin by β-cyclodextrin was investigated by 1H NMR. The continuous variation technique was used to evidence the formation of soluble 1:1 complex in aqueous solution. The association constant of vanillin with β-cyclodextrin has been obtained at 298 K by fitting the experimental chemical shifts differences, Δδobs = δfree - δobs of the observed guest and host protons, with a non-linear regression method. Besides the effective association constant, the fitting procedure allows a precise determination of all chemical shift parameters characterizing the pure complex. They can by used for an analysis of the geometry of the molecular complex in solution.

  11. Study of the inclusion interaction of HP-γ-cyclodextrin with bupropion and its analytical application

    NASA Astrophysics Data System (ADS)

    Misiuk, Wieslawa; Jasiuk, Emilia

    2014-02-01

    Inclusion complex formation between bupropion (BUP) and hydroxypropyl-γ-cyclodextrin (HP-γ-CD) was studied by Fourier transformation infrared (FT-IR), nuclear magnetic resonance (NMR) and UV spectroscopy. The main factors affecting inclusion interaction were discussed in detail. The inclusion complex of bupropion and hydroxypropyl-γ-cyclodextrin was studied at pH 5 in aqueous phase. Stoichiometry of the complex was found to be 1:1 and apparent formation constant (log K) was determined as 3.54 ± 0.01, suggesting a tendency of the drug to enter HP-γ-CD cavity. All obtained information proved the formation of BUP/HP-γ-CD inclusion complex. A significant enhancement of absorption intensity of bupropion in presence of HP-γ-CD was shown. Due to the property a sensitive spectrophotometric method was elaborated for determination of active substance in bulk solution. At optimum experimental conditions, a linear relationship between absorbance and concentration of bupropion is observed in range of 4-60 μg mL-1 with limit detection of 0.32 μg mL-1 and correlation coefficient of 0.9991. The proposed method was applied successfully to the determination of BUP in pharmaceutical preparations and the results were satisfactory in comparison to official method.

  12. Photochemical intracomplex reaction between [beta]-cyclodextrin and anthraquinone-2,6-disulfonic acid disodium salt in water solution

    NASA Astrophysics Data System (ADS)

    Petrova, S. S.; Kruppa, A. I.; Leshina, T. V.

    2005-05-01

    1D and 2D 1H NMR studies of anthraquinone-2,6-disulfonic acid disodium salt in the β-cyclodextrin solution have identified the inclusion complex formation. The association constant of AQDS-β-CD inclusion complex was determined as 800 ± 100 M -1. The selective intra-complex photo-oxidation of β-cyclodextrin at C6 position was detected by CIDNP method.

  13. Enhancement of 4-biphenylacetic acid bioavailability in rats by its beta-cyclodextrin complex after oral administration.

    PubMed

    Puglisi, G; Santagati, N A; Ventura, C A; Pignatello, R; Panico, A M; Spampinato, S

    1991-06-01

    4-Biphenylacetic acid, a potent non-steroidal anti-inflammatory agent forms a solid inclusion complex with beta-cyclodextrin in a 1:1 molar ratio, which exhibits better solubility and dissolution characteristics than the uncomplexed drug. Following oral administration of the complex to rats, quicker and higher drug plasma concentrations can be achieved than with the drug alone. Parallel studies, using the carrageenan paw oedema test, demonstrate a greater anti-inflammatory activity of the complex (ED50 of 2.9 mg kg-1 for the complex and of 6.2 mg kg-1 for the free drug). The complex displayed a better gastric tolerability in the rat than drug alone. PMID:1681057

  14. Influence of chemical structure of amphiphilic beta-cyclodextrins on their ability to form stable nanoparticles.

    PubMed

    Gèze, Annabelle; Aous, Soad; Baussanne, Isabelle; Putaux, JeanLuc; Defaye, Jacques; Wouessidjewe, Denis

    2002-08-21

    The aim of the study was to establish a correlation between the chemical structure of amphiphilic beta-cyclodextrins (beta-CDa) and their ability to form stable nanospheres. Amphiphilic derivatives were obtained according to an optimized well-known three-step synthesis. The selective acylation of the secondary face of beta-CD being well controlled, several beta-CDa presenting different substitution degree were synthesized. The self-organization properties of the derivatives were evaluated. The peracylated beta-CD, i.e. bearing 14 alkyl chains on the secondary hydroxyl groups, does not yield stable nanosphere suspension, even in the presence of a non ionic surfactant in the aqueous phase. However, the presence of partially acylated derivatives within the beta-CDa allows self-assembly into stable nanosphere suspension. PMID:12176268

  15. Improvement of the in vitro dissolution of praziquantel by complexation with alpha-, beta- and gamma-cyclodextrins.

    PubMed

    Becket, G; Schep, L J; Tan, M Y

    1999-03-01

    Although praziquantel (PZQ) is the primary drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery via the oral route. In spite of its poor solubility, PZQ is well absorbed across the gastrointestinal tract, but large doses are required to achieve adequate concentrations at the target sites. Improving the solubility would enable the parenteral route to be used, thereby avoiding significant first pass metabolism. The aqueous solubility of PZQ was improved by forming inclusion complexes with alpha-, beta- and gamma-cyclodextrins (CDs). These complexes were assessed and confirmed by solubility analysis, Fourier transform infrared analysis, elemental analysis, differential scanning calorimetry and mass spectrometry. Dissolution of PZQ from the alpha-, beta- and gamma-CD complexes was 2.6-, 5- and 8-fold greater, respectively, than that of the pure drug. However, only the beta-complex had a stability constant in the optimum range for pharmaceutical use, suggesting that the preferred complex for further development would be a water-soluble beta-CD derivative. PMID:10053203

  16. Synthesis and Characterization of the Inclusion Complex of β-cyclodextrin and Azomethine

    PubMed Central

    Sambasevam, Kavirajaa Pandian; Mohamad, Sharifah; Sarih, Norazilawati Muhamad; Ismail, Nor Atiqah

    2013-01-01

    A β-cyclodextrin (β-Cyd) inclusion complex containing azomethine as a guest was prepared by kneading method with aliquot addition of ethanol. The product was characterized by Fourier Transform Infrared (FTIR) spectrometer, 1H Nuclear Magnetic Resonance (1H NMR) and Thermogravimetric Analyzer (TGA), which proves the formation of the inclusion complex where the benzyl part of azomethine has been encapsulated by the hydrophobic cavity of β-Cyd. The interaction of β-Cyd and azomethine was also analyzed by means of spectrometry by UV-Vis spectrophotometer to determine the formation constant. The formation constant was calculated by using a modified Benesi-Hildebrand equation at 25 °C. The apparent formation constant obtained was 1.29 × 104 L/mol. Besides that, the stoichiometry ratio was also determined to be 1:1 for the inclusion complex of β-Cyd with azomethine. PMID:23434664

  17. Inclusion complex of Alizarin Red S with β-cyclodextrin: Synthesis, spectral, electrochemical and computational studies

    NASA Astrophysics Data System (ADS)

    Chin, Yuk Ping; Abdul Raof, Siti Farhana; Sinniah, Subathra; Lee, Vannajan Sanghiran; Mohamad, Sharifah; Abdul Manan, Ninie Suhana

    2015-03-01

    Inclusion complex formation of Alizarin Red S (ARS) with β-cyclodextrin was studied by UV-visible, Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), cyclic voltammetry (CV) and molecular modeling methods. FTIR and NMR results had justified that ARS was partly included into the β-CD cavity. The inclusion complex has 1:1 stoichiometry, where the apparent formation constant achieved was 4.137 × 103 L/mol using Benesi-Hildebrand equation. Cyclic voltammetry results shows the peak current decreased as the ARS molecule entered the hydrophobic cavity of β-CD. Molecular modeling results showed that the aromatic ring of the ARS entered into the secondary hydroxyl rim of the CD cavity was more thermodynamically favorable. The lowest stabilization energy, ΔE was -17.80 kcal/mol, and dipole-dipole interaction is was one of the driving forces for the inclusion complex formation.

  18. Antimicrobial and mechanical properties of β-cyclodextrin inclusion with essential oils in chitosan films.

    PubMed

    Sun, Xiuxiu; Sui, Siyao; Ference, Christopher; Zhang, Yifan; Sun, Shi; Zhou, Ninghui; Zhu, Wenjun; Zhou, Kequan

    2014-09-01

    Chitosan films incorporated with various concentrations of the complex of β-cyclodextrin and essential oils (β-CD/EO) were prepared and investigated for antimicrobial, mechanical, and physical properties. Four bacterial strains that commonly contaminate food products were chosen as target bacteria to evaluate the antimicrobial activity of the prepared films. The incorporation of β-CD/EO significantly increased the antimicrobial activities of the chitosan films against Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Listeria monocytogenes. It was also found that tensile strength (TS) of chitosan film was significantly increased with the incorporation of the β-cyclodextrin and 0.75% essential oils complex. The elongation at break (EB) decreased with the increasing concentrations of essential oils. Inclusion of the complex of β-cyclodextrin and 0.25% essential oils also significantly decreased water vapor permeability (WVP) of chitosan films. Our results suggest that chitosan films containing β-CD/EO could be used as active food-packaging material. PMID:25141280

  19. Inclusion of riboflavin in β-cyclodextrin: A fluorimetric and absorption spectrometric study

    NASA Astrophysics Data System (ADS)

    Roy, Dalim Kumar; Deb, Nipamanjari; Ghosh, Bankim Chandra; Mukherjee, Asok K.

    2009-07-01

    Formation of inclusion complexes between riboflavin and β-cyclodextrin (β-CD) with both 1:1 and 1:2 stoichiometry has been established by fluorimetric titration. However, in absorption spectrometric experiment, spectral change of riboflavin in the visible range could be observed only by taking β-CD at a much higher concentration (about 100 times) than riboflavin and under such condition only 1:2 complexes could be detected. Its formation constant ( K) was determined by a multiple linear regression analysis of the absorption data. The reliability of the K value was confirmed by the consistency achieved on analyzing the data at two different wavelengths.

  20. Stereoselective analysis of herbicides by capillary electrophoresis using sulfobutyl ether beta-cyclodextrin as chiral selector.

    PubMed

    Desiderio, C; Polcaro, C M; Fanali, S

    1997-02-01

    Capillary zone electrophoresis has been used for the enantiomeric separation of several herbicides. Different beta-cyclodextrin (CD) derivatives have been investigated for chiral separations and among them the negatively charged sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) proved to be effective for the stereo-selective resolutions of the investigated herbicides. The effect of CD concentration, buffer pH and organic modifier on effective mobilities, resolution and selectivity of the analytes have been studied. Addition of SBE-beta-CD (5-50 mg/mL) to the buffer at pH 9 resulted in a general increase of migration times as well as resolution. A CD concentration as low as 5 mg/mL was effective to completely resolve napropamide and ethofumesate enantiomers. Buffer solutions containing 40 mg/mL of SBE-beta-CD were chosen to study the effect of buffer pH (7, 8, and 9) on chiral separation of the herbicides. No great differences in resolution and effective mobilities have been found in the pH 7-9 range. The addition of different organic modifiers to the background electrolyte at pH 9, containing 20 mg/mL of SBE-beta-CD, showed different effects. Methanol was the most effective in improving resolution but in some cases total loss in enantiomeric separation was observed. The qualitative analysis of an enantiomerically pure herbicide (flamprop isopropyl) commercial preparation is also shown. PMID:9080130

  1. "Back to the Future": A New Look at Hydroxypropyl Beta-Cyclodextrins.

    PubMed

    Malanga, Milo; Szemán, Julianna; Fenyvesi, Éva; Puskás, István; Csabai, Katalin; Gyémánt, Gyöngyi; Fenyvesi, Ferenc; Szente, Lajos

    2016-09-01

    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. PMID:27317368

  2. Ternary complexation of carvedilol, beta-cyclodextrin and citric acid for mouth-dissolving tablet formulation.

    PubMed

    Pokharkar, Varsha; Khanna, Abhishek; Venkatpurwar, Vinod; Dhar, Sheetal; Mandpe, Leenata

    2009-06-01

    The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a ternary complex with beta-cyclodextrin and citric acid and to formulate its mouth-dissolving tablets. The rationale for preparing mouth-dissolving tablet of carvedilol was to make the drug available in a soluble form in the mouth, which would facilitate its absorption from the buccal cavity. This would help to overcome its first-pass metabolism and thereby improve bioavailability. Phase solubility studies revealed the ability of beta-cyclodextrin and citric acid to complex with carvedilol and significantly increase its solubility. Ternary complexation of carvedilol was carried out with beta-cyclodextrin and citric acid by physical mixing, kneading and spray drying methods and the prepared complexes were characterized by Fourier transform infra red spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and complexation efficiency. The complex obtained by the spray drying method resulted in highest complexation efficiency and a 110-fold increase in the solubility of carvedilol. The mouth-dissolving tablets formulated using the spray dried complex with suitable excipients showed 100 % dissolution within five minutes. Accelerated stability studies of mouth-dissolving tablets carried out as per ICH guidelines revealed that the tablets were stable. PMID:19564138

  3. Recognition ability and cytotoxicity of some oligosaccharidyl substituted beta-cyclodextrins.

    PubMed

    Attioui, F; al-Omar, A; Leray, E; Parrot-Lopez, H; Finance, C; Bonaly, R

    1994-01-01

    This paper reports a chemico-enzymatic synthesis of beta-CD derivatives. The recognition properties of these derivatives were tested using flocculating yeast and isolated lectins. It was observed that the substitution of beta-cyclodextrins with galactose end arms induces the better recognition by a cell-linked galactose-specific lectin. The physicochemical effects of the beta-CD derivatives on membranes were estimated using red blood cells and the effects on the viability of yeast and human rectal tumor cells were appreciated by measuring the mitochondrial deshydrogenase activity. The substitutions of the beta-CD ring by sugar antennae decrease the negative physicochemical effects of the beta-CD, ie their hemolytic properties. However, these substitutions induce significant modifications of the biological properties of the molecules, particularly the cytotoxicity and the growth of eukaryotic cells. PMID:7606211

  4. Evaluation of gastric toxicity of indomethacin acid, salt form and complexed forms with hydroxypropyl-beta-cyclodextrin on Wistar rats: histopathologic analysis.

    PubMed

    Ribeiro-Rama, A C; Figueiredo, Isabel Vitoria; Veiga, F; Castel-Branco, M M; Cabrita, A M S; Caramona, M M

    2009-12-01

    Indomethacin (IM) is a non-steroidal anti-inflammatory drug which inhibits prostaglandin biosynthesis. It is practically insoluble in water and has the capacity to induce gastric injury. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is an alkylated derivative of beta-CD with the capacity to form inclusion complexes with suitable molecules. IM is considered to form partial inclusion complexes with HP-beta-CD by enclosure of the p-chlorobenzoic part of the molecule in the cyclodextrin channel, reducing the adverse effects. The aim of this paper is to evaluate the gastric damage induced by the IM inclusion complex prepared by freeze-drying and spray-drying. A total of 135 Wistar rats weighing 224.4 +/- 62.5 g were put into 10 groups. They were allowed free access to water but were maintained fasted for 18 h before the first administration until the end of the experiment. IM acid-form, IM trihydrated-sodium-salt and IM-HP-beta-CD spray and freeze-dried, at normal and toxic doses, were administered through gastric cannula once/day for 3 days. Seventy-two hours after the first administration, the animals were sacrificed and the stomachs collected and prepared for morphological study by using the haematoxylin-eosin technique. Lesion indexes (rated 0/4) were developed and the type of injury was scored according to the severity of damage and the incidence of microscopic evidence of harm. Microscopic assessment demonstrated levels of injury with index one on 10-25%. The type of complexation method had different incidence but the same degree. The results show that IM inclusion complexation protects against gastric injury, reducing the incidence and the maximum degree of severity from 4 to 1, with a better performance of the spray-dried complex. PMID:19656206

  5. Spectroscopic study and antioxidant properties of the inclusion complexes of rosmarinic acid with natural and derivative cyclodextrins

    NASA Astrophysics Data System (ADS)

    Çelik, Saliha Esin; Özyürek, Mustafa; Tufan, Ayşe Nur; Güçlü, Kubilay; Apak, Reşat

    2011-05-01

    Measurement of total antioxidant activity/capacity of polyphenols in various solvent media necessitates the use of cyclodextrins to solubilize lipophilic antioxidants of poor aqueous solubility. The inclusion complexes of the slightly water soluble antioxidant, rosmarinic acid (RA), with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), 2-hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (M-β-CD) were investigated for the first time. The effect of cyclodextrins (CDs) on the spectral features of RA was measured in aqueous medium using UV-vis and steady-state fluorescence techniques by varying the concentrations of CDs. The molar stoichiometry of RA-CD inclusion complexes was verified as 1:1, and the formation constants of the complexes were determined from Benesi-Hildebrand equation using fluorescence spectroscopic data. Among the CDs, maximum inclusion ability was measured in the case of M-β-CD followed by HP-β-CD, HE-β-CD, β-CD and α-CD. Solid inclusion complexes were prepared by freeze drying, and their functional groups were analyzed by IR spectroscopy. Antioxidant capacity of CD-complexed rosmarinic acid was measured to be higher than that of the lone hydroxycinnamic acid by the CUPric Reducing Antioxidant Capacity (CUPRAC) method. The mechanism of the TAC increase was interpreted as the stabilization of the 1 - e oxidized o-catechol moiety of RA by enhanced intramolecular H-bonding in a hydrophobic environment provided by CDs, mostly by M-β-CD.

  6. Development of inclusion complex of brinzolamide with hydroxypropyl-β-cyclodextrin.

    PubMed

    Zhang, Ying; Ren, Ke; He, Zhiyao; Li, Huili; Chen, Tong; Lei, Yi; Xia, Shan; He, Gu; Xie, Yongmei; Zheng, Yu; Song, Xiangrong

    2013-10-15

    Glaucoma is an accumulative optic neuropathy resulted from increasing intraocular pressure. Brinzolamide (BRZ) is a kind of carbonic anhydrase inhibitors for glaucoma treatment. In this study, brinzolamide-hydroxypropyl-β-cyclodextrin (BRZ-HP-β-CD) inclusion complex was prepared by solvent evaporation method to improve the solubility of BRZ and enhance the therapeutic effect of BRZ. The formation of the inclusion complex was confirmed by Fourier transform infrared spectroscopy, differential scanning calorimeter and nuclear magnetic resonance spectroscopy. The solubility of BRZ increased about 10-fold after the formation of the BRZ-HP-β-CD inclusion complex. The in vitro corneal accumulative permeability of the inclusion complex increased 2.91-fold compared to the commercial available formulation (AZOPT(®)). In addition, BRZ-HP-β-CD inclusion complex (0.5% BRZ) had an equivalent efficiency of lowering intraocular pressure with AZOPT(®) (1% BRZ) in vivo. These results identified the BRZ-HP-β-CD inclusion complex might have a promising future as a novel formulation of BRZ for glaucoma treatment. PMID:23987393

  7. Possible enhancing mechanism of the cutaneous permeation of 4-biphenylylacetic acid by beta-cyclodextrin derivatives in hydrophilic ointment.

    PubMed

    Arima, H; Miyaji, T; Irie, T; Hirayama, F; Uekama, K

    1996-03-01

    The enhancing effects of heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) and 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) on the percutaneous absorption of 4-biphenylylacetic acid (BPAA), a nonsteroidal anti-inflammatory drug, in hydrophilic ointment were studied and compared with the parent beta-cyclodextrin (beta-CyD). 13C-NMR measurements suggested that the biphenyl group of BPAA is preferably included within the cavity of three beta-CyDs. The three beta-CyDs remarkably enhanced the release of BPAA from the hydrophilic ointment base and the in vitro cutaneous permeation, depending on the increase in solubility of BPAA in the ointment base. Pretreatment of the ointment containing DM-beta-CyD or HP-beta-CyD onto the isolated skin of hairless mice, however, provided no effects on the skin permeation of BPAA. When propylene glycol was used as a vehicle, both the release rate and cutaneous permeation parameters showed no appreciable difference between BPAA alone and its HP-beta-CyD complex, because the solubilities of BPAA and its HP-beta-CyD complex were almost comparable in the vehicle. The present results suggested that the enhancing effect of beta-CyDs on the percutaneous absorption of BPAA can be mainly ascribed to an increase in the solubility of BPAA in the hydrophilic ointment. PMID:8882455

  8. Binding geometry, stoichiometry, and thermodynamics of cyclomalto-oligosaccharide (cyclodextrin) inclusion complex formation with chlorogenic acid, the major substrate of apple polyphenol oxidase.

    PubMed

    Irwin, P L; Pfeffer, P E; Doner, L W; Sapers, G M; Brewster, J D; Nagahashi, G; Hicks, K B

    1994-03-18

    The inclusion complexes of cyclomaltohexaose (alpha-CD), cyclomaltoheptaose (beta-CD), cyclomaltooctaose (gamma-CD), and polymerized beta-CD (beta-CDn) with chlorogenic acid (CA), the major substrate of apple fruit polyphenol oxidase (PPO), were studied with regard to pH, ionic strength, and temperature in model buffer systems and apple juice. The thermodynamics of CD.CA inclusion complex formation, which were studied in solution using UV spectrophotometry, displayed enthalpy-entropy compensation typical of processes driven by solvation phenomena. We also found that the apparent association constants (K) of the CD.CA equilibrium were relatively insensitive to pH for beta-CD, compared to alpha- and gamma-CDs, but were subject to substantial enhancement at low ionic strengths. The beta-CD.CA inclusion complex was also characterized for binding geometry and stoichiometry at 9.4 T and 25 degrees C in 0.05 M Na phosphate buffer by 1H NMR spectroscopy. A 1:1 stoichiometric ratio for the complex was found using the method of continuous variations. 1H Spin-lattice relaxation and chemical-shift data indicate that the phenolic ring of CA docks within the cavity of beta-CD. The Ks for beta-, alpha-, and gamma-CD determined in apple juice, which contains a mixture of PPO substrates, were found to correlate with PPO activity-related data. Apple juice, treated with beta-CDn, did not brown until CA was added back. These latter findings strongly argue that the mechanism for inhibition of juice browning with cyclodextrins was mainly due to the binding of PPO substrates and not some other means such as enzyme inactivation via sequestration of Cu2+ by CDs. PMID:8194069

  9. Thermodynamics of complexation of dimethyl esters of tere-, iso-, and phthalic acids with alpha- and beta-cyclodextrins.

    PubMed

    Di Marino, Antonio; Mendicuti, Francisco

    2004-07-01

    Thermodynamics of inclusion of alpha- and beta-cyclodextrins (CDs) with three diester precursors of polyesters, dimethyl terephthalate (DMT), dimethyl isophthalate (DMI), and dimethyl phthalate (DMP) were studied with different fluorescence spectroscopy techniques. The stoichiometry, association constants, and other thermodynamics parameters were investigated from the fluorescence intensity decrease that takes place upon CD addition and temperature changes. Apart from DMP, which did not form a complex with alphaCD, all other systems showed 1:1 stoichiometry complexes with different stabilities. The complexes formed with the DMT guest are the most stable, whereas the stability constant for DMP:betaCD is the lowest. Binding constants are also larger for complexes formed with betaCD than for those formed with alphaCD. Fluorescence polarization, quenching, and lifetime measurements provide information about the structure of the complexes formed. This geometry explains the values of enthalpy and entropy changes during complexation. Van der Waals interactions seem to be involved in the formation of these complexes. PMID:15282048

  10. [Studies and application of fluorescence of metacycline enhanced by synergetic effect of beta-cyclodextrin and DBS].

    PubMed

    Ao, Deng-Gaowa; Si, Qin

    2008-11-01

    The fluorescence of metacycline enhanced by the synergetic effect of beta-cyclodextrin with anion surfactant sodium dodecylbenzene sulfonate (DBS) was studied. It was found that the fluorescence intensity of metacycline was greatly enhanced in the system of beta-CD-DBS. Based on this a new sensitive method for the determination of metacycline was established. The experiments indicated that MTC-beta-CD-DBS can form 1 : 1 : 1 ternary inclusion complex with apparent stability constant of 1 294 L2 x mol(-2), respectively. The fluorescence intensity was linearly related to the metacycline concentration in the range of 1.7 x 10(-7) to 8.8 x 10(-5) mol x L(-1) with a correlation coefficient of 0.996 6. The detection limit was 7.4 x 10(-9) mol x L(-1) this method was satisfactorily applied to the determination of metacycline in pharmaceutical preparations. The recovery was within the range of 95% to 106%. PMID:19271508

  11. Electrospinning of functional poly(methyl methacrylate) nanofibers containing cyclodextrin-menthol inclusion complexes

    NASA Astrophysics Data System (ADS)

    Uyar, Tamer; Nur, Yusuf; Hacaloglu, Jale; Besenbacher, Flemming

    2009-03-01

    Electrospinning of nanofibers with cyclodextrin inclusion complexes (CD-ICs) is particularly attractive since distinct properties can be obtained by combining the nanofibers with specific functions of the CD-ICs. Here we report on the electrospinning of poly(methyl methacrylate) (PMMA) nanofibers containing cyclodextrin-menthol inclusion complexes (CD-menthol-ICs). These CD-menthol-IC functionalized nanofibers were developed with the purpose of producing functional nanofibers that contain fragrances/flavors with high temperature stability, and menthol was used as a model fragrance/flavor material. The PMMA nanofibers were electrospun with CD-menthol-ICs using three type of CD: α-CD, β-CD, and γ-CD. Direct pyrolysis mass spectrometry (DP-MS) studies showed that the thermal evaporation of menthol occurred over a very high and a broad temperature range (100-355 °C) for PMMA/CDmenthol-IC nanowebs, demonstrating the complexation of menthol with the CD cavity and its high temperature stability. Furthermore, as the size of CD cavity increased in the order α-CD<β-CD<γ-CD, the thermal evolution of menthol shifted to higher temperatures, suggesting that the strength of interaction between menthol and the CD cavity is in the order γ-CD>β-CD>α-CD.

  12. Preparation, Physicochemical Characterization and I n - vitro Dissolution Studies of Diosmin-cyclodextrin Inclusion Complexes.

    PubMed

    Ai, Fengwei; Ma, Yingli; Wang, Jiayu; Li, Yanfeng

    2014-01-01

    Diosmin, a vascular-protecting agent, is practically insoluble in water, and its oral absorption is limited by its extremely low dissolution rate. In this study, β-cyclodextrin (βCD) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) were obtained to improve the solubility and dissolution rate of diosmin. Phase solubility studies of diosmin with βCD and HPβCD in distilled water were conducted to characterize the complexes in liquid state. The solid-state characterization of the complexes prepared with different methods was performed by fourier transform-infra red spectroscopy (FTIR), optical microscopy analyses, and differential scanning calorimetry (DSC). Dissolution studies were carried out in distilled water using US pharmacopeia dissolution rate testing equipment. The complexation of diosmin with βCD and HPβCD both indicated an AL type of phase-solubility diagrams, and the apparent stability constants (Kc) was found to be 222.13 and 200.08 M(-1), respectively. The Kc values indicated the βCD and HPβCD showed the similar equal complexation ability with diosmin, HPβCD provided higher solubility for diosmin due to its higher water solubility. The dissolution studies suggest that the inclusion complexes provide higher dissolution rate compared with the physical mixtures and the drug alone. Furthermore, the inclusion complex prepared by freeze drying method presented higher dissolution rate than kneading method. PMID:25587299

  13. Use of liquid crystals for imaging different inclusion abilities of α-cyclodextrin and β-cyclodextrin toward cetyltrimethyl ammonium bromide

    NASA Astrophysics Data System (ADS)

    Liao, Zhijian; Du, Sinan; Qin, Zhenli; Wang, Jinyan; Zuo, Fang; Luo, Jianbin

    2015-09-01

    We herein report a method for the imaging of different inclusion abilities of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) toward cetyltrimethyl ammonium bromide (CTAB) using liquid crystals (LCs). The optical transition from the dark to the bright state was caused by the inclusion interaction between CTAB and CDs. It was confirmed that α-CD formed more stable CTAB complexes than β-CD, leading to different optical responses of the LCs from the α-CD/CTAB and β-CD/CTAB systems. This method could be used to provide a visual method for selection of the correct CD molecules for interaction with surfactant molecules in recognition systems.

  14. NMR Study on the Inclusion Complexes of β-Cyclodextrin with Isoflavones.

    PubMed

    Zhao, Rui; Sandström, Corine; Zhang, Haiyang; Tan, Tianwei

    2016-01-01

    The structure of the inclusion complexes of β-cyclodextrin (β-CD) with daidzein and daidzin in D₂O were investigated using NMR spectroscopy. For the β-CD and daidzein system, two types of 1:1 complexes were formed with the daidzein deeply inserted into the CD cavity with different orientations. For the β-CD/daidzin system, a 1:1 complex was formed with the flavonoid part of daidzin entering the CD cavity from the wide rim. The inclusion complexes determined by NMR were constructed using molecular docking. Furthermore, the mixture of puerarin, daidzein and daidzin, which are the major isoflavonoid components present in Radix puerariae, was analyzed by diffusion-ordered spectroscopy (DOSY) alone and upon addition of β-CD in order to mimic chromatographic conditions and compare their binding affinities. PMID:27043500

  15. Study of inclusion complex of β-cyclodextrin and diphenylamine: Photophysical and electrochemical behaviors

    NASA Astrophysics Data System (ADS)

    Srinivasan, K.; Kayalvizhi, K.; Sivakumar, K.; Stalin, T.

    2011-06-01

    The photophysical, electrochemical and photoprototropic behaviors of diphenylamine (DPA) in aqueous β-cyclodextrin (β-CD) solution have been investigated using absorption spectroscopy and cyclic voltammetric techniques. Absorption of the neutral and cationic form of DPA is enhanced due to the formation of a 1:1 complex with β-CD. The formation of this complex has been confirmed by Benesi-Hildebrand plot and docking studies by RasMol tool methods. The solid complex of β-CD with DPA is investigated by FT-IR, XRD and AFM methods. The thermodynamic parameters (Δ G, Δ H and Δ S) of inclusion process are also determined. The p Ka values of neutral-monocation equilibria have been determined with absorption (conjugate acid-base) titrations. A mechanism is proposed to explain the inclusion process.

  16. Capillary electrophoretic behaviors of pharmacologically active xanthones from Securidaca inappendiculata with beta-cyclodextrin as a buffer additive.

    PubMed

    Bo, Tao; Huang, Yongfa; Yang, Xuedong; Li, Ke An; Liu, Huwei; Xu, Lizhen

    2003-04-01

    The capillary electrophoretic (CE) behaviors of ten xanthones in the presence of beta-cyclodextrin (CD) are investigated, and apparent analyte-selector binding constants between beta-CD and the xanthones in the CE running buffer are calculated to elucidate the migration order. Also, the separation selectivity with beta-CD additive is compared with that of sulfated beta-CD additive. It is indicated that beta-CD can greatly change the separation selectivity of xanthones, and the electrophoretic behaviors of xanthones are rather different when using beta-CD from that when using sulfated beta-CD as an additive. PMID:12803804

  17. Correlation of the solubility of several aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin with steric and hydrophobicity parameters.

    PubMed

    Demian, B A

    2000-10-01

    The solubility isotherms of nineteen aromatics and terpenes in aqueous hydroxypropyl-beta-cyclodextrin were determined to be straight lines. This is explained by the host-guest complexation which is characteristic for the whole class of cyclodextrins and derivatives. The slopes of the solubility isotherms correlate with Sterimol L and log P(ow) as descriptors of the steric fit and hydrophobicity match, in accord with the qualitative representation of the phenomenon. PMID:11093722

  18. Thermodynamic study on the effects of β-cyclodextrin inclusion with berberine

    NASA Astrophysics Data System (ADS)

    Yu, Jun-Sheng; Wei, Fang-Di; Gao, Wei; Zhao, Chang-Chun

    2002-01-01

    The fluorescence enhancement of berberine (Berb) as a result of complex with β-cyclodextrin (β-CD) is investigated. The association constants of α-CD and β-CD with Berb are 60 and 137 M -1 at 20 °C in pH 7.20 aqueous solution. Effects of temperature on the forming inclusion complexes of β-CD with Berb have been examined through using fluorescence titration. Enthalpy and entropy values calculated from fluorescence data are -33.7·kJ mol -1 and 74.3 J·mol -1·K -1, respectively. It was found that the dielectric constant of β-CD cavity is about 24 in a rough analogy with absolute alcohol. These results suggest that the extrusion of 'high energy water' molecules from the cavity of β-CD and hydrophobic interaction upon the inclusion complex formation are the main forces of the inclusion reaction. Effect of pH on the association of β-CD with Berb was also studied. Mechanism of the inclusion of β-CD with Berb is further studied by absorption and NMR measurements. Results show that β-CD forms a 1:1 inclusion complex with Berb.

  19. Inclusion of Paracetamol into β-cyclodextrin nanocavities in solution and in the solid state

    NASA Astrophysics Data System (ADS)

    El-Kemary, Maged; Sobhy, Saffaa; El-Daly, Samy; Abdel-Shafi, Ayman

    2011-09-01

    We report on steady-state UV-visible absorption and emission characteristics of Paracetamol, drug used as antipyretic agent, in water and within cyclodextrins (CDs): β-CD, 2-hydroxypropyl- β-CD (HP- β-CD) and 2,6-dimethyl- β-CD (Me- β-CD). The results reveal that Paracetamol forms a 1:1 inclusion complex with CD. Upon encapsulation, the emission intensity enhances, indicating a confinement effect of the nanocages on the photophysical behavior of the drug. Due to its methyl groups, the Me- β-CD shows the largest effect for the drug. The observed binding constant showing the following trend: Me- β-CD > HP- β-CD > β-CD. The less complexing effectiveness of HP- β-CD is due to the steric effect of the hydroxypropyl-substituents, which can hamper the inclusion of the guest molecules. The solid state inclusion complex was prepared by co-precipitation method and its characterization was investigated by Fourier transform infrared spectroscopy, 1H NMR and X-ray diffractometry. These approaches indicated that Paracetamol was able to form an inclusion complex with CDs, and the inclusion compounds exhibited different spectroscopic features and properties from Paracetamol.

  20. Some pharmaceutical and inclusion properties of 2-hydroxybutyl-β-cyclodextrin derivative.

    PubMed

    Ishiguro, Takako; Morishita, Eri; Iohara, Daisuke; Hirayama, Fumitoshi; Wada, Koki; Motoyama, Keiichi; Arima, Hidetoshi; Uekama, Kaneto

    2011-10-31

    2-Hydroxybutyl-β-cyclodextrins (HB-β-CyDs) with different degrees of substitution (D.S.) were prepared and their physicochemical and biological properties and solubilizing abilities were studied and compared with those of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD). The surface activity of HB-β-CyD was higher than that of HP-β-CyD (D.S. 5.6) and increased with its concentration and D.S. The moisture sorption of HB-β-CyD (D.S. 5.5) was less than that of HP-β-CyD (D.S. 5.6), because of the introduction of hydrophobic hydroxybutyl groups in a molecule. The hemolytic activity (rabbit erythrocytes) decreased in the order of 2,6-di-O-methyl-β-cyclodextrin (DM-β-CyD)>methyl-β-cyclodextrin (M-β-CyD)>HB-β-CyD (D.S. 5.5)>β-CyD>HP-β-CyD (D.S. 5.6). The hemolytic activity of HB-β-CyD increased with D.S. and HB-β-CyD induced echinocyte (or crenation), as well as DM-β-CyD does. It was suggested from the solubility study of membrane components that HB-β-CyD interacted predominantly with cholesterol in erythrocytes, resulting in the hemolysis. The inclusion ability of HB-β-CyD was higher than that of HP-β-CyD (D.S. 5.6), especially for poorly water-soluble drugs with long linear structures such as biphenylylacetic acid and flurbiprofen (FP). For example, HB-β-CyD formed the inclusion complex with FP in a molar ratio of 1:1, by including the biphenyl moiety in the host cavity. The dissolution rate of FP/HB-β-CyD (D.S. 5.5) complex was faster than that of HP-β-CyD (D.S. 5.6) complex. The results suggested that HB-β-CyDs have considerable pharmaceutical potential and can work as a fast-dissolving carrier for poorly water-soluble drugs. PMID:21839823

  1. Characterization of the complexation of diflunisal with hydroxypropyl-beta-cyclodextrin.

    PubMed

    Ugwu, S O; Alcala, M J; Bhardwaj, R; Blanchard, J

    1999-03-01

    The equilibrium dialysis method was applied to the determination of drug cyclodextrin stability constants using diflunisal and 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as a model system. Analysis of the data showed the existence of a linear Scatchard plot, indicative of the formation of a 1:1 diflunisal:HPBCD complex. The mean complexation constant (Kc) +/- S.D. was 3,892 +/- 360 M(-1). The stoichiometry of the complex was verified using the appropriate mass action law equation. The diflunisal:HPBCD complex was also investigated using titration microcalorimetry. A Kc of 3,394 M(-1) was obtained together with an enthalpy change (deltaH) of -20.76 kJ/mol(-1). The Kc values obtained here using the equilibrium dialysis and microcalorimetric methods were comparable to one reported previously using a potentiometric method (5,564 +/- 56 M(-1)). PMID:10704104

  2. Theoretical and Experimental Study of Inclusion Complexes of β-Cyclodextrins with Chalcone and 2',4'-Dihydroxychalcone.

    PubMed

    Sancho, Matias I; Andujar, Sebastian; Porasso, Rodolfo D; Enriz, Ricardo D

    2016-03-31

    The inclusion complexes formed by chalcone and 2',4'-dihydroxychalcone with β-cyclodextrin have been studied combining experimental (phase solubility diagrams, Fourier transform infrared spectroscopy) and molecular modeling (molecular dynamics, quantum mechanics/molecular mechanics calculations) techniques. The formation constants of the complexes were determined at different temperatures, and the thermodynamic parameters of the process were obtained. The inclusion of chalcone in β-cyclodextrin is an exothermic process, while the inclusion of 2',4'-dihydroxychalcone is endothermic. Free energy profiles, derived from umbrella sampling using molecular dynamics simulations, were constructed to analyze the binding affinity and the complexation reaction at a molecular level. Hybrid QM/MM calculations were also employed to obtain a better description of the energetic and structural aspects of the complexes. The intermolecular interactions that stabilize both inclusion complexes were characterized by means of quantum atoms in molecules theory and reduce density gradient method. The calculated interactions were experimentally observed using FTIR. PMID:26950264

  3. Studies on the Preparation, Characterization, and Solubility of 2-HP-β-Cyclodextrin-Meclizine HCl Inclusion Complexes

    PubMed Central

    George, SJ; Vasudevan, DT

    2012-01-01

    Meclizine HCl is a poorly water-soluble drug having a very slow-onset of action. The effect of 2-hydroxypropyl-β-cyclodextrins and β-cyclodextrins on its aqueous solubility and dissolution rate was investigated. The phase solubility profile indicated that the solubility of Meclizine HCl was significantly increased in the presence of both 2-hydroxypropyl-β-cyclodextrin and β- cyclodextrin; an extend of increase being more for 2-hydroxypropyl-β-cyclodextrin. It was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. The complexes formed were quite stable. The solid complexes prepared by physical mixtures, kneading methods, and co-precipitation methods were characterized using differential scanning calorimetry and FTIR. An in vitro study showed that the solubility and dissolution rate of Meclizine HCl were significantly improved by complexation with 2-hydroxypropyl-β-cyclodextrin. Tablet formulation using 1:1 kneading complex of Meclizine HCl and 2-hydroxypropyl-β-cyclodextrin with drug equivalent to 25 mg was prepared by a direct compression method. A dissolution study of prepared tablets was performed in 0.5% SLS in water (pH 7.0). Almost 96% drug was released from the formulation at the end of 30min. A comparison study of prepared tablets was done with marketed a Meclizine HCl 25 mg conventional tablet. From the results of dissolution study, it was found that the prepared formulation was showing better release, which was statistically significant P < 0.01 than a marketed tablet (paired t-test). Only 54% drug release was observed from the marketed tablet at the end of 30 min. Hence this study concludes that the solubility enhancement of Meclizine HCl could be successfully achieved using the inclusion complexation technique. PMID:23493156

  4. Studies on the Preparation, Characterization, and Solubility of 2-HP-β-Cyclodextrin-Meclizine HCl Inclusion Complexes.

    PubMed

    George, Sj; Vasudevan, Dt

    2012-10-01

    Meclizine HCl is a poorly water-soluble drug having a very slow-onset of action. The effect of 2-hydroxypropyl-β-cyclodextrins and β-cyclodextrins on its aqueous solubility and dissolution rate was investigated. The phase solubility profile indicated that the solubility of Meclizine HCl was significantly increased in the presence of both 2-hydroxypropyl-β-cyclodextrin and β- cyclodextrin; an extend of increase being more for 2-hydroxypropyl-β-cyclodextrin. It was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. The complexes formed were quite stable. The solid complexes prepared by physical mixtures, kneading methods, and co-precipitation methods were characterized using differential scanning calorimetry and FTIR. An in vitro study showed that the solubility and dissolution rate of Meclizine HCl were significantly improved by complexation with 2-hydroxypropyl-β-cyclodextrin. Tablet formulation using 1:1 kneading complex of Meclizine HCl and 2-hydroxypropyl-β-cyclodextrin with drug equivalent to 25 mg was prepared by a direct compression method. A dissolution study of prepared tablets was performed in 0.5% SLS in water (pH 7.0). Almost 96% drug was released from the formulation at the end of 30min. A comparison study of prepared tablets was done with marketed a Meclizine HCl 25 mg conventional tablet. From the results of dissolution study, it was found that the prepared formulation was showing better release, which was statistically significant P < 0.01 than a marketed tablet (paired t-test). Only 54% drug release was observed from the marketed tablet at the end of 30 min. Hence this study concludes that the solubility enhancement of Meclizine HCl could be successfully achieved using the inclusion complexation technique. PMID:23493156

  5. Liposomes incorporating cyclodextrin-drug inclusion complexes: Current state of knowledge.

    PubMed

    Gharib, Riham; Greige-Gerges, Hélène; Fourmentin, Sophie; Charcosset, Catherine; Auezova, Lizette

    2015-09-20

    Cyclodextrins (CDs) are cyclic oligosaccharides, consisting of glucopyranose units, which are able to form host-guest inclusion complexes with lipophilic molecules. The ability of CD to increase drug solubility may be used to increase drug entrapment in the aqueous compartment of liposomes and liposomes can protect CD/drug inclusion complexes until drug release. Liposomes are phospholipid vesicles composed of lipid bilayers enclosing one or more aqueous compartments. They have been widely used as safe and effective carriers for both hydrophilic and lipophilic drugs. However, lipophilic drugs incorporated in the membrane bilayers can be rapidly released, which limits the effectiveness of this drug delivery system. The coupling of both delivery systems by encapsulating CD/drug inclusion complex into liposomes is proposed to circumvent the drawbacks of each separate system. Here, we review the literature regarding the encapsulation of CD/drug inclusion complex into conventional, deformable and double loaded liposomes. The review highlights the characteristics of these systems and presents the advantages and disadvantages of each one. PMID:26050903

  6. β-Cyclodextrin inclusion complex: preparation, characterization, and its aspirin release in vitro

    NASA Astrophysics Data System (ADS)

    Zhou, Hui-Yun; Jiang, Ling-Juan; Zhang, Yan-Ping; Li, Jun-Bo

    2012-09-01

    In this work, the optimal clathration condition was investigated for the preparation of aspirin-β-cyclodextrin (Asp-β-CD) inclusion complex using design of experiment (DOE) methodology. A 3-level, 3-factor Box-Behnken design with a total of 17 experimental runs was used. The Asp-β-CD inclusion complex was prepared by saturated solution method. The influence on the embedding rate was investigated, including molar ratio of β-CD to Asp, clathration temperature and clathration time, and the optimum values of such three test variables were found to be 0.82, 49°C and 2.0 h, respectively. The embedding rate could be up to 61.19%. The formation of the bonding between -COOH group of Asp and O-H group of β-CD might play an important role in the process of clathration according to FT-IR spectra. Release kinetics of Asp from inclusion complex was studied for the evaluation of drug release mechanism and diffusion coefficients. The results showed that the drug release from matrix occurred through Fickian diffusion mechanism. The cumulative release of Asp reached only 40% over 24 h, so the inclusion complex could potentially be applied as a long-acting delivery system.

  7. Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability.

    PubMed

    Desai, Samixa; Poddar, Aditi; Sawant, Krutika

    2016-01-01

    The present investigation was aimed towards developing a beta-cyclodextrin (β-CD) solid dispersion (SD) based orally disintegrating tablet (ODT) of eslicarbazepine acetate (ESL), for improving the dissolution and providing fast onset of anti-epileptic action. Optimum ratio of ESL and β-CD was determined by Job's plot. Thereafter, solid dispersions were prepared by solvent evaporation method and evaluated for yield, assay, Differential scanning calorimetry (DSC), Fourier transform infra red spectroscopy (FTIR), X-ray diffraction (XRD), and in vitro dissolution. Optimized SD was compressed into ODT by direct compression using super disintegrants and evaluated for wetting time, drug content, in vitro drug release and in vivo studies. The results of DSC, FTIR and XRD analysis supported the formation of inclusion complex. An improved dissolution with 99.95 ± 2.80% drug release in 60 min was observed in comparison to 24.85 ± 2.96% release from a plain drug suspension. Tablets with crosspovidone as a super disintegrant showed the least disintegration time of 24.66 ± 1.52 s and higher in vitro drug release against marketed tablets. In vivo studies indicated that the formulated tablets had 2 times higher bioavailability than marketed tablets. Thus, the developed β-CD-ESL SD-ODT could provide faster onset of action and higher bioavailability, which would be beneficial in case of epileptic seizures. PMID:26478377

  8. A direct sensitized fluorimetric determination of 5,10,15,20-tetra(m-hydroxyphenyl)chlorin [m-THPC (Foscan)] in human plasma using a cyclodextrin inclusion complex.

    PubMed

    Desroches, M C; Kasselouri, A; Bourdon, O; Chaminade, P; Blais, J; Prognon, P

    2001-06-01

    The 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (m-THPC) (Foscan) is a photosensitizer used in the photodynamic therapy (PDT) of cancers which is currently under clinical trial. The formation of a m-THPC inclusion complex with dimethyl-beta-cyclodextrin (Me-beta-CD) in solution was demonstrated on the basis of circular dichroism experiments. A 1:2 complex stoichiometry was found and an inclusion constant beta 2 = 2.8(+/- 0.4) x 10(10) M-2 was determined. The formation of such a complex was shown to enhance the m-THPC fluorescence intensity. It could be exploited to improve the sensitivity of the direct m-THPC detection in human plasma. Optimization of the operating conditions shows that the best results were obtained by the addition of 100 microL of a concentrated Me-beta-CD solution (3.2 x 10(-2) M) to 1 mL plasma samples. Compared to the standard conditions, a 90% increase in sensitivity was obtained. The proposed analytical method which showed a linear response function [0-300 ng mL-1 (440 pM)] and a low limit of detection [1.5 ng mL-1 (2 pM) (S/N = 3)] appears, especially due to the absence of metabolism, a simple and specific method suitable for pharmacokinetics studies in patients. PMID:11445963

  9. Neutron diffraction of. cap alpha. ,. beta. and. gamma. cyclodextrins: hydrogen bonding patterns

    SciTech Connect

    Hingerty, B.E.; Klar, B.; Hardgrove, G.; Betzel, C.; Saenger, W.

    1983-01-01

    Cyclodextrins (CD's) are torus-shaped molecules composed of six (..cap alpha..), seven (..beta..) or eight (..gamma..) (1 ..-->.. 4) linked glucoses. ..cap alpha..-CD has been shown to have two different structures with well-defined hydrogen bonds, one tense and the other relaxed. An induced-fit-like mechanism for ..cap alpha..-CD complex formation has been proposed. Circular hydrogen bond networks have also been found for ..cap alpha..-CD due to the energetically favored cooperative effect. ..beta..-CD with a disordered water structure possesses an unusual flip-flop hydrogen bonding system of the type O-H H-O representing an equilibrium between two states; O-H O reversible H-O. ..gamma..-CD with a disordered water structure similar to ..beta..-CD also possesses the flip-flop hydrogen bond. This study demonstrates that hydrogen bonds are operative in disordered systems and display dynamics even in the solid state.

  10. Vitamin A Palmitate-β-cyclodextrin inclusion complexes: characterization, protection and emulsification properties.

    PubMed

    Vilanova, Neus; Solans, Conxita

    2015-05-15

    The interest in the production of foods enriched with vitamins, in order to prevent diseases related with their deficiency, has recently increased. However, the low stability and the low water solubility of certain vitamins make difficult their incorporation in foodstuff, especially in water-based formulations. This limitation is typically overcome by using encapsulating systems such as cyclodextrins. In this paper the formation of water-soluble inclusion complexes of Vitamin A Palmitate with β-cyclodextrins, without the use of organic solvents, is described. The objective was to increase the water solubility of Vitamin A Palmitate and its stability against different external factors to eventually enrich aqueous-based products. The stability of Vitamin A Palmitate in the complexes towards temperature, oxygen and UV light was investigated. All results showed a notably increase of Vitamin A Palmitate water solubility and stability in front of those variables when encapsulated. The surface activity of the complex suggests its possible use as stabilizer in emulsion formulations. PMID:25577116

  11. Effect of inclusion complexation of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges on solubility, in vitro release and stability studies.

    PubMed

    Shende, Pravin K; Gaud, R S; Bakal, Ravindra; Patil, Dipmala

    2015-12-01

    The objective of the present work was to develop inclusion complexes of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges to enhance their solubility and stability and to prolong release using different methods that included physical mixing, kneading and sonication. Particle size, zeta potential, encapsulation efficiency, stability study results, in vitro and in vivo drug release study results, FTIR, DSC and XRPD were used as characterization parameters. SEM (Scanning Electron Microscope) studies revealed that the particle sizes of the inclusion complexes of meloxicam were within the range of 350 ± 5.69-765 ± 13.29 nm. The zeta potentials were sufficiently high to obtain stable formulations. In vitro and in vivo release studies revealed the controlled release of meloxicam from the nanosponges for 24h. The interaction of the meloxicam with the nanosponges was confirmed by FTIR and DSC. A XRPD study revealed that the crystalline nature of meloxicam was changed to an amorphous form due to the complexation with the nanosponges. A stability study revealed that the meloxicam nanosponges were stable. Therefore, β-cyclodextrin-based nanosponges represent a novel approach for the controlled release of meloxicam for anti-inflammatory and analgesic effects. PMID:26364091

  12. Microanalyses of beta-cyclodextrin in plasma by high-performance liquid chromatography.

    PubMed

    Koizumi, K; Kubota, Y; Okada, Y; Utamura, T

    1985-05-31

    Procedures for the micro-determination of beta-cyclodextrin (beta-CyD) in plasma were investigated by four methods using high-performance liquid chromatography (HPLC). In methods A and B, underivatized beta-CyD was detected with a refractive index detector and determined by the absolute calibration graph method. An NH2-bonded silica/acetonitrile-water system was used in A and a C18-bonded silica/methanol-water system in B. In method C, the percarbanilate of beta-CyD was separated on a C8-bonded silica column with acetonitrile-water and determined using gamma-CyD as the internal standard with a UV detector at 231 nm. In method D, the per[1-14C]acetate of beta-CyD was fractionated on a silica column with n-hexane-ethanol containing 1% of water and the radioactivity of each fraction was measured with a liquid scintillation counter. gamma-CyD was used as the internal standard. Interfering plasma proteins were removed by centrifugal ultrafiltration with an MPS-1 micro-partition system. Method B was superior to the other methods with respect to ease of sample preparation, sensitivity and time required for analysis. The cumulative amount of beta-CyD in the mesenteric vein absorbed from the rat intestinal lumen after administration of phenobarbital-beta-CyD complex in a closed loop method was determined by the use of method B. PMID:4019695

  13. Electrochemical study of mono-6-thio-beta-cyclodextrin/ferrocene capped on gold nanoparticles: characterization and application to the design of glucose amperometric biosensor.

    PubMed

    Chen, Ming; Diao, Guowang

    2009-12-15

    A novel amperometric glucose sensor based on inclusion complex of mono-6-thio-beta-cyclodextrin/ferrocene capped on gold nanoparticles (GNPs/CD-Fc) and glucose oxidase (GOD) was described. The inclusion complex of mono-6-thio-beta-cyclodextrin/ferrocene capped on gold nanoparticles played an effective role of an electron shuttle and allowed the detection of glucose at 0.25 V (versus SCE), with dramatically reduced interference from easily oxidizable constituents. The sensor (GNPs/CD-Fc/GOD) showed a relatively fast response time (5 s), low detection limit (15 microM, S/N=3), and high sensitivity (ca. 18.2 mA M(-1) cm(-2)) with a linear range of 0.08-11.5mM of glucose. The excellent sensitivity was possibly attributed to the presence of the GNPs/CD-Fc film that can provide a convenient electron tunneling between the protein and the electrode. In addition, the biosensor demonstrated high anti-interference ability, stability and natural life. The good stability and natural life can be attributed to the following two aspects: on the one hand, the fabrication process was mild and no damage was made on the enzyme molecule, on the other hand, the GNPs possessed good biocompatibility that could retain the bioactivity of the enzyme molecules immobilized on the electrode. PMID:19836557

  14. [Preparation and investigation of gemfibrozil + dimethyl-beta-cyclodextrin products and solid dosage forms].

    PubMed

    Hassan, Bin Hassan; Aigner, Zoltán; Kása, Péter; Hódi, Klára; Eros, István

    2005-01-01

    Gemfibrozil is a lipid-regulating active substance. Dimethyl-beta-cyclodextrin products were prepared from this sparingly soluble pharmacon by means of methods such as physical mixing, kneading, spray drying and ultrasonication. Solid dosage forms (hydroxypropylmethyl cellulose /HPMC/ capsules and tablets) were prepared from the selected products on the basis of their dissolution profile and the in vitro membrane diffusion results. This publication details the results of electronmicroscopic morphological studies, particle size analysis and wetting contact angle determinations, and also the preparation and examination of the resulting solid dosage forms. PMID:16318236

  15. Characterization and Enhanced Antioxidant Activity of the Cysteinyl β-Cyclodextrin-Baicalein Inclusion Complex.

    PubMed

    Kim, Hwanhee; Yiluo, Hu; Park, Seyeon; Lee, Jae Yung; Cho, Eunae; Jung, Seunho

    2016-01-01

    Baicalein is a type of flavonoid isolated from the roots of a medicinal plant, Scutellaria baicalensis. Although it has attracted considerable attention due to its antiviral, anti-tumor, and anti-inflammatory activities, its limited aqueous solubility inhibits the clinical application of this flavonoid. The present study aimed to prepare and characterize a host-guest complex in an effort to improve the solubility and antioxidant activity of baicalein. The host molecule is a macrocyclic β-cyclodextrin (β-CD) functionalized with cysteine for a synergetic effect. The structure of the synthesized cysteinyl β-CD was analyzed using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. The inclusion complex with baicalein was studied by UV-vis, NMR spectroscopy, scanning electron microscopy, and X-ray powder diffractometry. The formed cysteinyl β-CD/baicalein inclusion complex efficiently improved the solubility and antioxidant ability of baicalein. Therefore, we suggest that the present cysteinyl β-CD is a potential host molecule for inclusion complexation and for bioavailability augmentation. PMID:27240335

  16. Quercetin/β-cyclodextrin inclusion complex embedded nanofibres: Slow release and high solubility.

    PubMed

    Aytac, Zeynep; Kusku, Semran Ipek; Durgun, Engin; Uyar, Tamer

    2016-04-15

    Electrospinning of polyacrylic acid (PAA) nanofibres (NF) incorporating β-cyclodextrin inclusion complex (β-CD-IC) of quercetin (QU) was performed. Here, β-CD was used as not only the crosslinking agent for PAA nanofibres but also as a host molecule for inclusion of QU. The phase solubility test showed enhanced solubility of QU due to the inclusion complexation; in addition, the stoichiometry of QU/β-CD-IC was determined to be 1:1. Computational modelling studies confirmed that 1:1 and 1:2 complex formation are desirable; 1:1 complex formation was chosen to have higher weight loading of QU. SEM images showed that PAA/QU/β-CD-IC-NF were bead-free and uniform. XRD indicated that PAA/QU/β-CD-IC-NF were amorphous in nature without the crystalline peaks of QU. Comparative results revealed that the release profile of QU from PAA/QU/β-CD-IC-NF was much slower but greater in total than from PAA/QU/β-CD-IC-film. Moreover, high antioxidant activity and photostability of QU was achieved in PAA/QU/β-CD-IC-NF. PMID:26617028

  17. Investigation on the inclusion and toxicity of acriflavine with cyclodextrins: A spectroscopic approach

    NASA Astrophysics Data System (ADS)

    Manivannan, C.; Meenakshi Sundaram, K.; Sundararaman, M.; Renganathan, R.

    2014-03-01

    Acriflavine hydrochloride (AFN) is a prospective drug worn in the eradication of HIV1 infection. The toxicity and adverse side effects renders the potent drug to limits its usage. However, to overcome the dilemma we have aimed to select carriers with great complexation efficiencies in different cyclodextrins (CDs) of varying cavity size. The interaction of AFN with α, β and γ-CDs were investigated using absorption and steady state as well as lifetime measurements. From the obtained data it was found that AFN fits in the cavity of α and β-CDs but unable to form inclusion complex with γ-CD. The effect of quencher molecules during the inclusion phenomena of AFN with CDs was explored via steady state measurements. The nature of binding forces responsible for the inclusion of AFN with CDs was discussed by using thermodynamic parameters. Using Benesi-Hildebrand equation the stoichiometry of AFN with CDs was predominantly found to be 1:1. To get deeper in situ, the in vitro toxicity of AFN and its complexation product were probed by Artemia salina sp. The toxicity of AFN was reduced when complexed with α and β-CDs.

  18. Chitosan-graft-beta-cyclodextrin scaffolds with controlled drug release capability for tissue engineering applications.

    PubMed

    Prabaharan, M; Jayakumar, R

    2009-05-01

    Biodegradable scaffolds composed of chitosan-g-beta-cyclodextrin (chit-g-beta-CD) were prepared by freeze-drying method as synthetic extracellular matrices to fill the gap during the healing process. Due to the presence of beta-CD, these scaffolds can be used as a matrix for drug loading and controlled release. The morphology, swelling and drug release properties of the scaffolds were found to be dependent on the extent of cross-linking density in the scaffolds. The drug dissolution profile showed that chit-g-beta-CD scaffolds provided a slower release of the entrapped ketoprofen than chitosan scaffold. The MTT assay showed that there is no obvious cytotoxicity of chit-g-beta-CD scaffolds cross-linked with 0.01 M of glutaraldehyde against the fibroblasts (L929) cells. These results suggest that chit-g-beta-CD scaffolds may become a potential biodegradable active filling material with controlled drug release capability, which provide a healthy environment and enhance the surrounding tissue regeneration. PMID:19428461

  19. Liquid chromatography analysis of monosubstituted sulfobutyl ether-beta-cyclodextrin isomers on porous graphitic carbon.

    PubMed

    Jacquet, Romain; Pennanec, Rodolphe; Elfakir, Claire; Lafosse, Michel

    2004-10-01

    The retention behaviour of the three positional isomers of monosubstituted sulfobutyl ether-beta-cyclodextrin was investigated on a porous graphitic carbon (PGC) column. The influence of the mobile phase composition (nature and concentration of organic and electronic modifiers) was studied as well as the effect of column temperature. These hydrophilic and anionic analytes were highly retained on the PGC stationary phase compared to octadecyl bonded phases. The retention is mainly governed by a reversed-phase mechanism with electronic interaction playing a secondary role. An increase in solute retention and efficiency with temperature was observed. Successful isocratic separation with satisfactory baseline resolution of the three isomers of monosubstituted sulfobutyl ether-beta-cyclodextrin was achieved at 75 degrees C on a Hypercarb column by using ammonium acetate as electronic modifier in water-acetonitrile (83:17). The chromatographic methodology developed can be easily used for relative quantification of each isomer within a mixture and can be applied for semi-preparative purification of each one. The evaporative light scattering detector allows the detection of these non UV-visible absorbing molecules. PMID:15537080

  20. Characterizing the natural canthaxanthin/2-hydroxypropyl-β-cyclodextrin inclusion complex.

    PubMed

    Gharibzahedi, Seyed Mohammad Taghi; Razavi, Seyed Hadi; Mousavi, Mohammad

    2014-01-30

    A fundamental study on the phase-solubility, storage stability and antioxidant activity of the inclusion complex of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) with canthaxanthin (CTX) biosynthesized by Dietzia natronolimnaea HS-1 in a continuous bioreactor was designed. A variety of in vitro chemical methods including reducing power (RP), nitrite-scavenging activity (NSA), and 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and hydroxyl radicals scavenging capacities was used to determine antioxidant activities of the CTX and CTX/HP-β-CD complex. Results revealed that the apparent stability constant of the inclusion complex was 669 M(-1) in a 1:1 stoichiometric ratio. The complexation of CTX with HP-β-CD significantly improved its water solubility and storage stability. An increased dose-dependent manner was found for the NSA and RP values of the CTX and CTX/HP-β-CD complex. The CTX/HP-β-CD complex showed higher scavenging capacity than native CTX against DPPH, ABTS and hydroxyl radicals. It can be used as a promising strategy to improve the food application of CTX. PMID:24299886

  1. Characterization of the Supermolecular Structure of Polydatin/6-O-α-Maltosyl-β-cyclodextrin Inclusion Complex.

    PubMed

    Liu, Benguo; Li, Yun; Xiao, Huizhi; Liu, Yonglan; Mo, Haizhen; Ma, Hanjun; Liang, Guizhao

    2015-06-01

    Polydatin is the main bioactive ingredient in many medicinal plants, such as Hu-zhang (Polygonum cuspidatum), with many bioactivities. However, its poor aqueous solubility restricts its application in functional food. In this work, 6-O-α-Maltosyl-β-cyclodextrin (Malt-β-CD), a new kind of β-CD derivative was used to enhance the aqueous solubility and stability of polydatin by forming the inclusion complex. The phase solubility study showed that polydatin and Malt-β-CD could form the complex with the stoichiometric ratio of 1:1. The supermolecular structure of the polydatin/Malt-β-CD complex was characterized by ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), thermogravimetric/differential scanning calorimetry (TG/DSC), and proton nuclear magnetic resonance ((1) H-NMR) spectroscopy. The changes of the characteristic spectral and thermal properties of polydatin suggested that polydatin could entrap inside the cavity of Malt-β-CD. Furthermore, to reasonably understand the complexation mode, the supermolecular structure of polydatin/Malt-β-CD inclusion complex was postulated by a molecular docking method based on Autodock 4.2.3. It was clearly observed that the ring B of polydatin oriented toward the narrow rim of Malt-β-CD with ring A and glucosyl group practically exposed to the wide rim by hydrogen bonding, which was in a good agreement with the spectral data. PMID:25916244

  2. An inclusion complex of eugenol into β-cyclodextrin: Preparation, and physicochemical and antifungal characterization.

    PubMed

    Gong, Liang; Li, Taotao; Chen, Feng; Duan, Xuewu; Yuan, Yunfei; Zhang, Dandan; Jiang, Yueming

    2016-04-01

    The inclusion of eugenol (EG) into β-cyclodextrin (βCD), its structural characterization and antifungal activity, and mode of action for control of Peronophythora litchii in postharvest fresh litchi fruits is described. Nuclear magnetic resonance spectra revealed chemical shifts in H-3 and H-5 protons of βCD, indicating EG inclusion into the lipophilic cavity of βCD. In vitro assays showed βCD-EG significantly inhibited P. litchii colony growth in a concentration- and time-dependent manner (MIC100=0.2g). In vivo assays showed βCD-EG significantly (p<0.05) reduced the decay index of treated fresh litchi fruits. After exposure to βCD-EG, the surface of P. litchii hyphae and/or sporangiophores became wrinkled, with folds and breakage observed by scanning electron microscopy. Damage to hyphal and/or sporangiophore cell walls and membrane structures post-treatment with βCD-EG was confirmed by transmission electron microscopy. Therefore, βCD-EG shows great potential as a controlled-release agent against P. litchii. PMID:26593497

  3. A 5,7-dimethoxyflavone/hydroxypropyl-β-cyclodextrin inclusion complex with anti-butyrylcholinesterase activity.

    PubMed

    Songngam, Supachai; Sukwattanasinitt, Mongkol; Siralertmukul, Krisana; Sawasdee, Pattara

    2014-10-01

    This study aimed to improve the water solubility of 5,7-dimethoxyflavone (5,7-DMF) isolated from Kaempferia parviflora by complexation with 2-hydroxypropyl-β-cyclodextrin (HPβ-CD). The phase solubility profile of 5,7-DMF in the presence of HPβ-CD was classified as AL-type and indicated a 1:1 mole ratio. Differential scanning colorimetry, X-ray diffraction, NMR and SEM analyses supported the formation of a 5,7-DMF/HPβ-CD inclusion complex involving the A ring of 5,7-DMF inside the HPβ-CD cavity. This is the first example of CD inclusion with the A ring of non-hydroxyl flavones. The stability and binding constants of the complexes were determined using the phase solubility and UV-vis absorption spectroscopy, respectively. The water solubility of 5,7-DMF was increased 361.8-fold by complexation with HPβ-CD and overcame the precipitation problem observed in aqueous buffers, such as during in vitro anti-butyrylcholinesterase activity assays. The 1:1 mole ratio of the 5,7-DMF/HPβ-CD complex showed a 2.7-fold higher butyrylcholinesterase inhibitory activity (in terms of the IC50 value) compared to the non-complexed compound. PMID:24879292

  4. Using molecular recognition of beta-cyclodextrin to determine molecular weights of low-molecular-weight explosives by MALDI-TOF mass spectrometry.

    PubMed

    Zhang, Min; Shi, Zhen; Bai, Yinjuan; Gao, Yong; Hu, Rongzu; Zhao, Fenqi

    2006-02-01

    This study presents a novel method for determining the molecular weights of low molecular weight (MW) energetic compounds through their complexes of beta-cyclodextrin (beta-CD) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in a mass range of 500 to 1700 Da, avoiding matrix interference. The MWs of one composite explosive composed of 2,6-DNT, TNT, and RDX, one propellant with unknown components, and 14 single-compound explosives (RDX, HMX, 3,4-DNT, 2,6-DNT, 2,5-DNT, 2,4,6-TNT, TNAZ, DNI, BTTN, NG, TO, NTO, NP, and 662) were measured. The molecular recognition and inclusion behavior of beta-CD to energetic materials (EMs) were investigated. The results show that (1) the established method is sensitive, simple, accurate, and suitable for determining the MWs of low-MW single-compound explosives and energetic components in composite explosives and propellants; and (2) beta-CD has good inclusion and modular recognition abilities to the above EMs. PMID:16406809

  5. Solution structures of 1:1 complexes of oxyphenonium bromide with beta- and gamma-cyclodextrins.

    PubMed

    Funasaki, Noriaki; Sumiyoshi, Tomoko; Ishikawa, Seiji; Neya, Saburo

    2004-01-01

    The solution structures of complexes of oxyphenonium bromide (OB) with beta- and gamma-cyclodextrins (beta- and gamma-CDs, respectively) in deuterium oxide have been investigated by 500 MHz proton NMR spectroscopy and molecular mechanics calculations. The chemical shifts induced by complex formation provide the 1:1 binding constants and the chemical shift variations, DeltadeltaOB-CD, with complexation for the protons of OB and the CDs. The observed binding constants are very close to those obtained by other methods and are in the following order: beta-CD > gamma-CD > alpha-CD. Initial structures of the complexes are constructed on the basis of the ROESY spectra and the DeltadeltaOB-CD values and are optimized by molecular mechanics calculations. The intermolecular distances between the protons of OB and CD calculated for these structures are well-correlated with the observed ROESY intensities. The cyclohexyl group of OB penetrates deeply into a beta-CD cavity, and the phenyl group is close to the wide rim of the cavity. The phenyl and cyclohexyl groups of OB are both incorporated into a gamma-CD cavity. Furthermore, these structures of the complexes are consistent with the suppression of bitter taste and basic hydrolysis of OB by CDs and the polarity of binding sites of OB. PMID:15832513

  6. Inclusion complexes of quercetin with three β-cyclodextrins derivatives at physiological pH: Spectroscopic study and antioxidant activity

    NASA Astrophysics Data System (ADS)

    Liu, Min; Dong, Lina; Chen, Aiju; Zheng, Yan; Sun, Dezhi; Wang, Xu; Wang, Bingquan

    2013-11-01

    Properties of the inclusion complexes of quercetin (QUE) with sulfobutyl ether-β-cyclodextrin (SBE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and methylated-β-cyclodextrin (M-β-CD) in tris-HCl buffer solutions of pH 7.40 were investigated. The stoichiometry and thermodynamic parameters for the complexation process (stability constants K, Gibbs free energy change ΔG, enthalpy change ΔH and entropy change ΔS) were determined using phase-solubility and fluorescence spectra analysis. The thermodynamic studies indicated that the inclusion reactions between QUE and the three β-CDs are enthalpy-driven processes. Proton nuclear magnetic resonance spectroscopy indicated that B-ring, C-ring, and part of A-ring of QUE interact with the cavity of β-CDs. The antioxidant activity of QUE and its inclusion complexes were determined by the scavenging of stable radical DPPH*. The results showed that the complexed QUE/CDs were more effective than free QUE, with the QUE/SBE-β-CD complex as the best form.

  7. Nanosuspensions Containing Oridonin/HP-β-Cyclodextrin Inclusion Complexes for Oral Bioavailability Enhancement via Improved Dissolution and Permeability.

    PubMed

    Zhang, Xingwang; Zhang, Tianpeng; Lan, Yali; Wu, Baojian; Shi, Zhihai

    2016-04-01

    Chemotherapy via oral route of anticancer drugs offers much convenience and compliance to patients. However, oral chemotherapy has been challenged by limited absorption due to poor drug solubility and intestinal efflux. In this study, we aimed to develop a nanosuspension formulation of oridonin (Odn) using its cyclodextrin inclusion complexes to enhance oral bioavailability. Nanosuspensions containing Odn/2 hydroxypropyl-β-cyclodextrin inclusion complexes (Odn-CICs) were prepared by a solvent evaporation followed by wet media milling technique. The nanosuspensions were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and dissolution. The resulting nanosuspensions were approximately 313.8 nm in particle size and presented a microcrystal morphology. Nanosuspensions loading Odn-CICs dramatically enhanced the dissolution of Odn. Further, the intestinal effective permeability of Odn was markedly enhanced in the presence of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and poloxamer. Bioavailability studies showed that nanosuspensions with Odn-CICs can significantly promote the oral absorption of Odn with a relative bioavailability of 213.99% (Odn suspensions as reference). Odn itself possesses a moderate permeability and marginal intestinal metabolism. Thus, the enhanced bioavailability for Odn-CIC nanosuspensions can be attributed to improved dissolution and permeability by interaction with absorptive epithelia and anti-drug efflux. Nanosuspensions prepared from inclusion complexes may be a promising approach for the oral delivery of anticancer agents. PMID:26187778

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

    PubMed

    Silva, Nataly; Muñoz, Camila; Diaz-Marcos, Jordi; Samitier, Josep; Yutronic, Nicolás; Kogan, Marcelo J; Jara, Paul

    2016-12-01

    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 Abstract Atomic Force Microscopy observation of the disintegration of a cyclodextrin inclusion compound by gold nanoparticles photothermal effect. PMID:27053258

  9. Inclusion complex of erlotinib with sulfobutyl ether-β-cyclodextrin: Preparation, characterization, in silico, in vitro and in vivo evaluation.

    PubMed

    Devasari, Naresh; Dora, Chander Parkash; Singh, Charan; Paidi, Sharan Reddy; Kumar, Vivek; Sobhia, Masilamani Elizabeth; Suresh, Sarasija

    2015-12-10

    The aim of the study was to investigate the impact of erlotinib sulfobutyl ether beta-cyclodextrin complex (ERL-SBE-β-CD) on ERL dissolution rate and oral bioavailability. Preliminary comparative phase solubility study indicated ERL exhibited maximum solubility in SBE-β-CD solution. Optimal experimental design confirmed freeze drying of SBE-β-CD:ERL in 1:1.05 molar ratio as the optimum method. Differential scanning calorimetry (DSC), Fourier transformation infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), proton nuclear magnetic resonance ((1)H NMR) and two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY NMR) confirmed the inclusion complexation. The in silico computational study, employed to analyze the comparative interactions of ERL with SBE-β-CD and β-CD, indicated ease of ERL-SBE-β-CD complexation. In vitro dissolution and in vivo bioavailability studies further confirmed the ERL-SBE-β-CD as a valuable approach to enhance ERL oral bioavailability with 3.6-fold increase in relative oral bioavailability with higher Cmax (134.29 ± 36.51 vs. 42.36 ± 1.75 μg/ml) and AUC0-∞ (2103.47 ± 156.75 vs.580.43 ± 71.91 μg/ml h) over the free drug. The complex exhibited 3.2-fold increase in Cmax with 5.4-fold decrease in Tmax (0.5 ± 0.2 vs. 2.7 ± 0.8h) in comparison to pure ERL. Thus, ERL-SBE-β-CD complexation exhibits a potential to enhance oral bioavailability of ERL leading to reduce dose and dose-related side effects. PMID:26428157

  10. Spectral and electrochemical study of host-guest inclusion complex between 2,4-dinitrophenol and β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Srinivasan, K.; Stalin, T.; Sivakumar, K.

    The formation of host-guest inclusion complex of 2,4-dinitrophenol (2,4-DNP) with nano-hydrophobic cavity of β-cyclodextrin (β-CD) in solution phase was studied by UV-visible spectrophotometer and electrochemical method (cyclic voltammetry, CV). The prototropic behaviors of 2,4-DNP with and without β-CD and the ground state acidity constant (pKa) of host-guest inclusion complex (2,4-DNP-β-CD) were studied. The binding constant of inclusion complex at 303 K was calculated using Benesi-Hildebrand plot and thermodynamic parameter (ΔG) was also calculated. The solid inclusion complex formation between β-CD and 2,4-DNP was confirmed by 1H NMR, FT-IR, XRD and SEM analysis. A schematic representation of this inclusion process is proposed by molecular docking studies using PatchDock server.

  11. [Study on the inclusion compound of avermectin by infrared spectroscopy].

    PubMed

    Shen, Wen; Zhang, Guang-Hua; Guo, Ning; Li, Yun-Tao

    2014-05-01

    This study was designed to investigate the formation and effect of inclusion complex of Avermectin-beta-cyclodextrin based on the accommodation property of beta-cyclodextrin's molecular cavity. The inclusion complex of Averrnectin-beta-cyclodextrin was prepared using saturated solution method and high performance liquid chromatography (HPLC) was employed to determine its entraping efficiency. The formation of Avermectin-beta-cyclodextrin inclusion complex was also demonstrated by infrared spectroscopy(IR). The change of chemical structure produced by photocatalysis of Abamectin was analyzed and the effect of inclusion complex to strengthen the photolysis stability of Abamectin's chemical structure was studied. The results show that the entraping efficiency of the inclusion complex was 40. 5%. The IR analysis presents that the intermolecular hydrogen bond was formed in the Avermectin-beta-cyclodextrin inclusion complex, indicating the composition effect was different from physical mixture. The lactones structure of Avermectin Bla can be photodecomposed and disrupted. After decomposition, the infrared stretching vibration peak of C-O-C structure disappeared and the lactone bond was significantly broken. The lactones structure of avermectin Bla was covered by the inclusion molecular loci in beta-cyclodextrin after the formation of avermectin-beta-cyclodextrin inclusion complex, providing a good photophobic protection for C-O-C structure in the macrocyclic lactone structure of avermectin Bla and improving the photostability of avermectin Bla molecule. The innovation of this study is that the structure and the characters of the prepared avermectin-beta-cyclodextrin inclusion complex were analyzed using spectrum methods. This inclusion complex is expected to be the ideal intermediate in the construction of protective controlled release formulation of avermectin. PMID:25095407

  12. Stability and spatial arrangement of the 2,4-dichlorophenoxyacetic acid and β-cyclodextrin inclusion compound: A theoretical study

    NASA Astrophysics Data System (ADS)

    Pereira, Robson A.; Anconi, Cleber P. A.; Nascimento, Clebio S.; De Almeida, Wagner B.; Dos Santos, Hélio F.

    2015-07-01

    The present letter reports results from a comprehensive theoretical analysis of the inclusion process involving 2,4-dichlorophenoxyacetic acid (2,4-D) and β-cyclodextrin (β-CD) for which the experimental data of formation is available. Spatial arrangement and stabilization energies were evaluated in gas phase and aqueous solution through density functional theory (DFT) and through the use of SMD implicit solvation approach. The discussed methodology was applied to predict the stability and identify the most favorable form (deprotonated or neutral) as well as the most probable spatial arrangement of the studied inclusion compound.

  13. Quantification of Randomly-methylated-{beta}-cyclodextrin effect on liposome: An ESR study

    SciTech Connect

    Grammenos, A.; Bahri, M.A.; Guelluy, P.H.; Piel, G.; Hoebeke, M.

    2009-12-04

    In the present work, the effect of Randomly-methylated-{beta}-cyclodextrin (Rameb) on the microviscosity of dimyristoyl-L-{alpha} phosphatidylcholine (DMPC) bilayer was investigated using the electron spin resonance (ESR) technique. The ability of Rameb to extract membrane cholesterol was demonstrated. For the first time, the percentage of cholesterol extracted by Rameb from cholesterol doped DMPC bilayer was monitored and quantified throughout a wide Rameb concentration range. The effect of cholesterol on the inner part of the membrane was also investigated using 16-doxyl stearic acid spin label (16-DSA). 16-DSA seems to explore two different membrane domains and report their respective microviscosities. ESR experiments also establish that the presence of 30% of cholesterol in DMPC liposomes suppresses the jump in membrane fluidity at lipids phase-transition temperature (23.9 {sup o}C).

  14. Preparation and characterization of polystyrene microspheres in the presence of beta-cyclodextrin.

    PubMed

    Wang, Wei; Deng, Yan; Zhang, Liming; Fu, Juan; Lu, Zhuoxuan; Xu, Lijian

    2012-09-01

    Using styrene as raw material, potassium persulfate as an initiator, beta-cyclodextrin as a stabilizer, polystyrene microspheres were successfully prepared with nice monodisperse feature by means of soap-free emulsion polymerization method. Experimental studies were performed in detail to check the effect of the synthesis process of the microspheres, the stabilizer dosage, monomer concentration, and initiator dosage on the particle size and distribution, the microstructures were characterized with SEM, TEM, infrared (IR) and the particle size distribution investigation. The results show that the appropriate changes in amount of stabilizer and monomer concentration and dosage of initiator can result in a different particle size and polystyrene microspheres with good monodispersity were finally obtained. PMID:23035453

  15. Beta-cyclodextrins conjugated magnetic Fe3O4 colloidal nanoclusters for the loading and release of hydrophobic molecule

    NASA Astrophysics Data System (ADS)

    Lv, Shaonan; Song, Yubei; Song, Yaya; Zhao, Zhigang; Cheng, Changjing

    2014-06-01

    Herein, we report a facile method to prepare beta-cyclodextrin (β-CD)-conjugated magnetic Fe3O4 colloidal nanocrystal clusters (Fe3O4@GLY-CD) using (3-glycidyloxypropyl) trimethoxysilane (GLY) as the intermediate linker. The resulting Fe3O4@GLY-CD was characterized by several methods including Fourier transform infrared (FT-IR) spectroscopy, field-emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and vibrating sample magnetometer (VSM). In addition, the loading and release properties of the synthesized Fe3O4@GLY-CD for the hydrophobic molecule 8-anilino-1-naphthalenesulfonic acid ammonium salt (ANS) were also investigated. The results show that the Fe3O4@GLY-CD has a spherical structure with an average diameter of 186 nm and high saturated magnetism of 51.2 emu/g. The grafting of β-CD onto Fe3O4 colloidal nanocrystal clusters can markedly increase the loading capacity of ANS because of β-CD/ANS inclusion complex formation. The in vitro delivery profile shows that the release of ANS from the Fe3O4@GLY-CD nanosystem exhibits an initial burst followed by a slow and steady release. Moreover, Fe3O4@GLY-CD also demonstrates a temperature-dependent release behavior for ANS owing to the effect of temperature on the association constants of β-CD/ANS inclusion complexes. The developed magnetic hybrid nanomaterial is expected to find potential applications in several fields including separation science and biomedicine.

  16. Studies on the inclusion behavior of 9-Aminoacridine into cyclodextrins: Spectroscopic and theoretical evidences

    NASA Astrophysics Data System (ADS)

    Manivannan, C.; Vijay Solomon, R.; Venuvanalingam, P.; Renganathan, R.

    2013-02-01

    9-Aminoacridine (9-AA) is an important attractive pharmaceutical drug employed as chemotheraptic agent for wound dressings. However, 9-AA possesses limited solubility and rapid metabolic decomposition renders this potential drug to limit its applications. Here we propose cyclodextrins (CDs) as a drug carrier to improve the bioavailability, solubility of 9-AA. The interaction between 9-AA and CDs (α-CD and β-CD) has been studied using UV-Vis absorption, steady state time resolved fluorescence, 1H NMR and FT-IR spectroscopy techniques. The spectroscopic measurements show that 9-AA does not form stable complex with α-CD and also confirmed by DFT calculations. On the other hand, 9-AA forms inclusion complex with β-CD in a 1:1 stoichiometry ratio. Our DFT results suggest that 9-AA stabilizes inside the CD environment through hydrogen bonding that has unambiguously confirmed by AIM analysis. Thus our studies provide a useful insights in the development of Aminoacridine based drugs & its delivery through a suitable carrier like CDs.

  17. Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes.

    PubMed

    Nutho, Bodee; Khuntawee, Wasinee; Rungnim, Chompoonut; Pongsawasdi, Piamsook; Wolschann, Peter; Karpfen, Alfred; Kungwan, Nawee; Rungrotmongkol, Thanyada

    2014-01-01

    In the present study, our aim is to investigate the preferential binding mode and encapsulation of the flavonoid fisetin in the nano-pore of β-cyclodextrin (β-CD) at the molecular level using various theoretical approaches: molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. The molecular docking suggested four possible fisetin orientations in the cavity through its chromone or phenyl ring with two different geometries of fisetin due to the rotatable bond between the two rings. From the multiple MD results, the phenyl ring of fisetin favours its inclusion into the β-CD cavity, whilst less binding or even unbinding preference was observed in the complexes where the larger chromone ring is located in the cavity. All MM- and QM-PBSA/GBSA free energy predictions supported the more stable fisetin/β-CD complex of the bound phenyl ring. Van der Waals interaction is the key force in forming the complexes. In addition, the quantum mechanics calculations with M06-2X/6-31G(d,p) clearly showed that both solvation effect and BSSE correction cannot be neglected for the energy determination of the chosen system. PMID:25550745

  18. Enhancement of enantioselectivity in chiral capillary electrophoresis using hydroxypropyl-beta-cyclodextrin as chiral selector under molecular crowding conditions induced by dextran or dextrin.

    PubMed

    Fu, Qifeng; Yang, Fengqing; Chen, Hua; Xia, Zhining

    2014-10-01

    Molecular crowding is a new approach to enhance the retention properties and selectivity of molecularly imprinted polymers. In this work, this concept was first applied to chiral CE to enhance its enantioselectivity. A model system, enantioseparation of salbutamol using hydroxypropyl-beta-cyclodextrin as chiral selector in the presence of dextran or dextrin as crowding-inducing agents, was chosen to demonstrate its potency. Some parameters, especially the concentration of crowding-inducing agents and cyclodextrins were investigated intensively. Moreover, based on fluorescence spectroscopy and affinity CE, it was found that the presence of crowding-inducing agents could promote the association of enantiomers with cyclodextrins and intensify the interacting differences of two enantiomers with cyclodextrins. As a result, the essential concentration of cyclodextrins to make the enantiomers reach baseline separation was significantly decreased with the aid of molecular crowding. This study shows that molecular crowding is an effective strategy to enhance the enantioselectivity of cyclodextrin in chiral CE. PMID:24981718

  19. Detoxification of nerve agents by a substituted beta-cyclodextrin: application of a modified biological assay.

    PubMed

    Wille, T; Tenberken, O; Reiter, G; Müller, S; Le Provost, R; Lafont, O; Estour, F; Thiermann, H; Worek, F

    2009-11-30

    Chemical warfare agents (nerve agents) are still available and present a real threat to the population. Numerous in vitro and in vivo studies showed that various nerve agents, e.g. tabun and cyclosarin, are resistant towards standard therapy with atropine and oxime. Based on these facts we applied a modified biological assay for the easy, semi-quantitative testing of the detoxifying properties of the beta-cyclodextrin derivative CD-IBA. Cyclosarin, sarin, tabun and VX were incubated with CD-IBA for 1-50 min at 37 degrees C, then an aliquot was added to erythrocyte acetylcholinesterase (AChE) and the percentage of AChE inhibition was determined. The validity of the assay was confirmed by concomitant quantification of tabun by GC-MS. Different concentrations of cyclosarin were detoxified by CD-IBA in a concentration-dependent velocity. The ability to detoxify various nerve agents decreased in the order cyclosarin>sarin>tabun>VX. Hereby, no detoxification of VX could be detected. Sarin was detoxified in a biphasic reaction with a fast reduction of inhibitory potential in the first phase and a slower detoxification in the second phase. CD-IBA detoxified tabun in a one phase decay and, compared to cyclosarin and sarin, a longer half-life was determined with tabun. The modified biological assay is appropriate for the initial semi-quantitative screening of candidate compounds for the detoxification of nerve agents. The beta-cyclodextrin derivative CD-IBA demonstrated its ability to detoxify different nerve agents. PMID:19800384

  20. Antilithiasic effect of beta-cyclodextrin in LPN hamster: comparison with cholestyramine.

    PubMed

    Boehler, N; Riottot, M; Férézou, J; Souidi, M; Milliat, F; Sérougne, C; Smith, J L; Lutton, C

    1999-04-01

    Beta-Cyclodextrin (BCD), a cyclic oligosaccharide that binds cholesterol and bile acids in vitro, has been previously shown to be an effective plasma cholesterol lowering agent in hamsters and domestic pigs. This study examined the effects of BCD as compared with cholestyramine on cholesterol and bile acid metabolism in the LPN hamster model model for cholesterol gallstones. The incidence of cholesterol gallstones was 65% in LPN hamsters fed the lithogenic diet, but decreased linearly with increasing amounts of BCD in the diet to be nil at a dose of 10% BCD. In gallbladder bile, cholesterol, phospholipid and chenodeoxycholate concentrations, hydrophobic and lithogenic indices were all significantly decreased by 10% BCD. Increases in bile acid synthesis (+110%), sterol 27-hydroxylase activity (+106%), and biliary cholate secretion (+140%) were also observed, whereas the biliary secretion of chenodeoxycholate decreased (-43%). The fecal output of chenodeoxycholate and cholate (plus derivatives) was increased by +147 and +64%, respectively, suggesting that BCD reduced the chenodeoxycholate intestinal absorption preferentially. Dietary cholestyramine decreased biliary bile acid concentration and secretion, but dramatically increased the fecal excretion of chenodeoxycholate and cholate plus their derivatives (+328 and +1940%, respectively). In contrast to BCD, the resin increased the lithogenic index in bile, induced black gallstones in 34% of hamsters, and stimulated markedly the activities of HMG-CoA reductase (+670%), sterol 27-hydroxylase (+310%), and cholesterol 7alpha-hydroxylase (+390%). Thus, beta-cyclodextrin (BCD) prevented cholesterol gallstone formation by decreasing specifically the reabsorption of chenodeoxycholate, stimulating its biosynthesis and favoring its fecal elimination. BCD had a milder effect on lipid metabolism than cholestyramine and does not predispose animals to black gallstones as cholestyramine does in this animal model. PMID:10191297

  1. Characterization and dynamic properties for the solid inclusion complexes of β-cyclodextrin and perfluorooctanoic acid.

    PubMed

    Karoyo, Abdalla H; Sidhu, Paul; Wilson, Lee D; Hazendonk, Paul

    2013-07-11

    The structural characterization and dynamic properties of solid-state inclusion complexes (ICs) formed between β-cyclodextrin (β-CD; host) and perfluorooctanoic acid (PFOA; guest) were investigated using (13)C NMR spectroscopy. The 1:1 and 2:1 host/guest solid-state complexes were prepared using a modified dissolution method to obtain complexes with high phase purity. These complexes were further characterized using differential scanning calorimetry (DSC), FT-IR spectroscopy, powder X-ray diffraction (PXRD), (19)F directpolarization (DP), and (13)C cross-polarization (CP) with magic-angle spinning (MAS) NMR spectroscopy. The (19)F → (13)C CP results provided unequivocal support for the formation of well-defined inclusion compounds. The phase purity of the complexes formed between β-CD and PFOA were assessed using the (19)F DP NMR technique at variable temperature (VT) and MAS at 20 kHz. The complexes were found to be of high phase purity when prepared in accordance with the modified dissolution method. The motional dynamics of the guest in the solid complexes were assessed using T1/T2/T1ρ relaxation NMR methods at ambient and VT conditions. The relaxation data revealed reliable and variable guest dynamics for the 1:1 versus 2:1 complexes at the VTs investigated. The motional dynamics of the guest molecules involve an ensemble of axial motions of the whole chain and 120° rotational jumps of the methyl (CF3) group at the termini of the perfluorocarbon chain. The axial and rotational dynamics of the guest in the 1:1 and 2:1 complexes differ in distribution and magnitude in accordance with the binding geometry of the guest within the host. PMID:23713518

  2. Impact of beta-cyclodextrin and resistant starch on bile acid metabolism and fecal steroid excretion in regard to their hypolipidemic action in hamsters.

    PubMed

    Trautwein, E A; Forgbert, K; Rieckhoff, D; Erbersdobler, H F

    1999-01-29

    To examine the impact on bile acid metabolism and fecal steroid excretion as a mechanism involved in the lipid-lowering action of beta-cyclodextrin and resistant starch in comparison to cholestyramine, male golden Syrian hamsters were fed 0% (control), 8% or 12% of beta-cyclodextrin or resistant starch or 1% cholestyramine. Resistant starch, beta-cyclodextrin and cholestyramine significantly lowered plasma total cholesterol and triacylglycerol concentrations compared to control. Distinct changes in the bile acid profile of gallbladder bile were caused by resistant starch, beta-cyclodextrin and cholestyramine. While cholestyramine significantly reduced chenodeoxycholate independently of its taurine-glycine conjugation, beta-cyclodextrin and resistant starch decreased especially the percentage of taurochenodeoxycholate by -75% and -44%, respectively. As a result, the cholate:chenodeoxycholate ratio was significantly increased by 100% with beta-cyclodextrin and by 550% with cholestyramine while resistant starch revealed no effect on this ratio. beta-Cyclodextrin and resistant starch, not cholestyramine, significantly increased the glycine:taurine conjugation ratio demonstrating the predominance of glycine conjugated bile acids. Daily fecal excretion of bile acids was 4-times higher with 8% beta-cyclodextrin and 19-times with 1% cholestyramine compared to control. beta-Cyclodextrin and cholestyramine also induced a 2-fold increase in fecal neutral sterol excretion, demonstrating the sterol binding capacity of these two compounds. Resistant starch had only a modest effect on fecal bile acid excretion (80% increase) and no effect on excretion of neutral sterols, suggesting a weak interaction with intestinal steroid absorption. These data demonstrate the lipid-lowering potential of beta-cyclodextrin and resistant starch. An impaired reabsorption of circulating bile acids and intestinal cholesterol absorption leading to an increase in fecal bile acid and neutral sterol

  3. Host-guest inclusion systems of daidzein with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD): Preparation, binding behaviors and water solubility

    NASA Astrophysics Data System (ADS)

    Deng, Yinghui; Pang, Yanhua; Guo, Yafei; Ren, Yufeng; Wang, Fen; Liao, Xiali; Yang, Bo

    2016-08-01

    Daidzein is an isoflavone of naturally abundance existing in plants and foods which has attracted much attention for its significant benefits on human health. However, its application was severely limited by its poor solubilities, instability and low bioavailability. To overcome these drawbacks, inclusion complexes of daidzein with two cyclodextrin (CD) derivatives, i.e., 2-hydropropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin (SBE-β-CD) were prepared and characterized both in solution and solid state by 1D and 2D NMR, XRD, SEM and elemental analyses. Fluorescence spectroscopy and the Job plot were used to demonstrate a mainly 1:1 inclusion mode between daidzein and CDs. Their thermal stabilities were evaluated with TG and DSC experiments. Moreover, water solubility of daidzein was significantly improved by inclusion complexation with CDs. These results might suggest valuable approaches to developments of new pharmaceutical formulations of daidzein.

  4. Integrated immobilized cell reactor-adsorption system for beta-cyclodextrin production: a model study using PVA-cryogel entrapped Bacillus agaradhaerens cells.

    PubMed

    Martins, Rita F; Plieva, Fatima M; Santos, Ana; Hatti-Kaul, Rajni

    2003-09-01

    Production of cyclodextrins (CDs) by immobilized cells of the alkaliphilic Bacillus agaradhaerens LS-3C with integrated product recovery was studied. The microorganism was entrapped in polyvinyl alcohol-cryogel beads and used as a convenient source of immobilized cyclodextrin glycosyltransferase (CGTase). On activation by incubation in the cultivation medium containing 1% (w/v) starch, the entrapped cells multiplied and secreted CGTase with an activity of 2-3 mg beta-cyclodextrin h(-1) g(-1) beads. The immobilized biocatalyst exhibited maximum activity at pH 9 and 50 degrees C, and formed cyclodextrins comprising 92-94% beta-CD and remaining alpha-CD. The cyclodextrin product from the immobilized cell bioreactor was continuously recovered by adsorption to Amberlite XAD-4 in a recycle batch mode. The product adsorption was facilitated at low temperature while hot water was used for elution. PMID:14571979

  5. Studies on inclusion complexation between 4,4‧-dihydroxybiphenyl and β-cyclodextrin by experimental and theoretical approach

    NASA Astrophysics Data System (ADS)

    Paramasivaganesh, K.; Srinivasan, K.; Manivel, A.; Anandan, S.; Sivakumar, K.; Radhakrishnan, S.; Stalin, T.

    2013-09-01

    The inclusion complex formation between 4,4‧-dihydroxybiphenyl (DHBP) and β-cyclodextrin (β-CD) in aqueous state were studied by UV-Visible spectroscopy, Fluorescence spectroscopy and electrochemical study (cyclic voltammetry, CV). The solid state complex between β-CD and DHBP were characterized by FT-IR, XRD techniques and SEM morphological studies. The β-CD: DHBP inclusion complex obtained by molecular docking studies was in good correlation with the results obtained through experimental methods. The binding constant of 'β-CD: DHBP' inclusion complex was calculated using Benesi-Hildebrand plot at 303 K. The experimental results indicated that the inclusion process is an exergonic and spontaneous process. The point energy, stabilization energy upon complexation and frontier molecular orbital's were obtained. The calculation results correlates well with the docking and experimental observations.

  6. Structure of the complex of beta-cyclodextrin with beta-naphthyloxyacetic acid in the solid state and in aqueous solution.

    PubMed

    Kokkinou, A; Yannakopoulou, K; Mavridis, I M; Mentzafo, D

    2001-05-01

    The structure of the complex of beta-cyclodextrin (cyclomaltoheptaose) with beta-naphthyloxyacetic acid was studied in solid state by X-ray diffraction and in aqueous solution by 1H NMR spectroscopy. The complex crystallizes in the channel mode, space group C2, with a stoichiometry of 2:1; two beta-cyclodextrin molecules related by a twofold crystal axis form dimers, in the cavity of which one guest molecule is found on average. The above stoichiometry indicates one guest per beta-CD dimer statistically oriented over two positions or two guest molecules in pi-pi interactions in half of the beta-CD dimers and the rest of the beta-CD dimers empty. In addition, occupancy of 0.5 for the guest per every beta-CD dimer is in accord with the occupancy of the two disordered primary hydroxyls. These two hydroxyl groups, to which the carboxylic oxygen atoms of the guest are hydrogen bonded, point towards the interior of the beta-CD cavity. In aqueous solution, the 1H NMR spectroscopic study indicated that there is a mixture of complexes with host-guest stoichiometries both 1:1 and 2:1. PMID:11403091

  7. Formulation and In-vitro Evaluation of Orally Disintegrating Tablets of Olanzapine-2-Hydroxypropyl-β-Cyclodextrin Inclusion Complex

    PubMed Central

    Ajit Shankarrao, Kulkarni; Dhairysheel Mahadeo, Ghadge; Pankaj Balavantrao, Kokate

    2010-01-01

    The aim of this study was to design orally disintegrating tablets of Olanzapine and to complex Olanzapine with 2-hydroxypropyl-β- cyclodextrin with special emphasis on disintegration and dissolution studies. Phase solubility studies demonstrated the formation of 1:1 molar inclusion complex by kneading method. Tablets were prepared by using superdisintegrants namely, sodium starch glycolate, croscarmellose sodium, crospovidone, tulsion 339, and indion 414. Complex was characterized using infrared spectroscopy, drug content estimation, saturated solubility study, diffrerential scanning calorimetry and X-ray diffractometry. 5% w/w croscarmellose sodium showed the minimum disintegration time 39 ± 1.76 sec and in-vitro drug release 99.19 ± 0.18% within 6 min. In general, solubility of Olanzapine can be improved by complexing with 2-hydroxypropyl-β- cyclodextrin. Croscarmellose sodium can be used for faster disintegration of tablets. PMID:24381598

  8. 1H NMR studies on the hydrogen-bonding network in mono-altro-beta-cyclodextrin and its complex with adamantane-1-carboxylic acid.

    PubMed

    Hakkarainen, Birgit; Fujita, Kahee; Immel, Stefan; Kenne, Lennart; Sandström, Corine

    2005-06-13

    The hydrogen-bond network in mono-altro-beta-cyclodextrin and in its inclusion complex with adamantane-1-carboxylic acid were investigated by (1)H NMR spectroscopy using the chemical shifts, temperature coefficients and vicinal coupling constants of the exchangeable hydroxy protons. The chemical shifts of the 3-OH signals indicated that the hydrogen-bond network between the 2-OH and 3-OH groups was disturbed not only on each side of the altrose residue, but also along the whole dextrin chain. Upon addition of adamantane-1-carboxylic acid, altrose underwent a conformational change from the (1)C(4) to the (O)S(2) form, allowing a more continuous belt of hydrogen bonding, as evidenced by the downfield shift experienced by the 3-OH proton signals of the glucose residues. PMID:15885670

  9. Enantioseparation of mandelic acid derivatives by high performance liquid chromatography with substituted β-cyclodextrin as chiral mobile phase additive and evaluation of inclusion complex formation

    PubMed Central

    Tong, Shengqiang; Zhang, Hu; Shen, Mangmang

    2014-01-01

    The enantioseparation of ten mandelic acid derivatives was performed by reverse phase high performance liquid chromatography with hydroxypropyl-β-cyclodextrin (HP-β-CD) or sulfobutyl ether-β-cyclodextrin (SBE-β-CD) as chiral mobile phase additives, in which inclusion complex formations between cyclodextrins and enantiomers were evaluated. The effects of various factors such as the composition of mobile phase, concentration of cyclodextrins and column temperature on retention and enantioselectivity were studied. The peak resolutions and retention time of the enantiomers were strongly affected by the pH, the organic modifier and the type of β-cyclodextrin in the mobile phase, while the concentration of buffer solution and temperature had a relatively low effect on resolutions. Enantioseparations were successfully achieved on a Shimpack CLC-ODS column (150×4.6 mm i.d., 5 μm). The mobile phase was a mixture of acetonitrile and 0.10 mol L-1 of phosphate buffer at pH 2.68 containing 20 mmol L-1 of HP-β-CD or SBE-β-CD. Semi-preparative enantioseparation of about 10 mg of α-cyclohexylmandelic acid and α-cyclopentylmandelic acid were established individually. Cyclodextrin-enantiomer complex stoichiometries as well as binding constants were investigated. Results showed that stoichiomertries for all the inclusion complex of cyclodextrin-enantiomers were 1:1. PMID:24893270

  10. Encapsulation of gallic acid/cyclodextrin inclusion complex in electrospun polylactic acid nanofibers: Release behavior and antioxidant activity of gallic acid.

    PubMed

    Aytac, Zeynep; Kusku, Semran Ipek; Durgun, Engin; Uyar, Tamer

    2016-06-01

    Cyclodextrin-inclusion complexes (CD-ICs) possess great prominence in food and pharmaceutical industries due to their enhanced ability for stabilization of active compounds during processing, storage and usage. Here, CD-IC of gallic acid (GA) with hydroxypropyl-beta-cyclodextrin (GA/HPβCD-IC) was prepared and then incorporated into polylactic acid (PLA) nanofibers (PLA/GA/HPβCD-IC-NF) using electrospinning technique to observe the effect of CD-ICs in the release behavior of GA into three different mediums (water, 10% ethanol and 95% ethanol). The GA incorporated PLA nanofibers (PLA/GA-NFs) were served as control. Phase solubility studies showed an enhanced solubility of GA with increasing amount of HPβCD. The detailed characterization techniques (XRD, TGA and (1)H-NMR) confirmed the formation of inclusion complex between GA and HPβCD. Computational modeling studies indicated that the GA made an efficient complex with HPβCD at 1:1 either in vacuum or aqueous system. SEM images revealed the bead-free and uniform morphology of PLA/GA/HPβCD-IC-NF. The release studies of GA from PLA/GA/HPβCD-IC-NF and PLA/GA-NF were carried out in water, 10% ethanol and 95% ethanol, and the findings revealed that PLA/GA/HPβCD-IC-NF has released much more amount of GA in water and 10% ethanol system when compared to PLA/GA-NF. In addition, GA was released slowly from PLA/GA/HPβCD-IC-NF into 95% ethanol when compared to PLA/GA-NF. It was also observed that electrospinning process had no negative effect on the antioxidant activity of GA when GA was incorporated in PLA nanofibers. PMID:27040215

  11. Effect of Tween 80 and beta-cyclodextrin on degradation of decabromodiphenyl ether (BDE-209) by White rot fungi.

    PubMed

    Zhou, Juan; Jiang, Weiying; Ding, Juan; Zhang, Xingding; Gao, Shixiang

    2007-12-01

    The environmental safety of decabromodiphenyl ether (BDE-209), a widely used flame retardant, has been the topic of controversial discussions during the past several years. Degradation of BDE-209 into lower brominated diphenyl ether congeners, exhibiting a higher bioaccumulation potential, has been a critical issue. White rot fungi are known to degrade a wide variety of recalcitrant pollutants. In this work, white rot fungi were used to degrade BDE-209 in liquid culture medium, and the effects of Tween 80 and beta-cyclodextrin on BDE-209 degradation by white rot fungi were evaluated. On the basis of these results, it appears that BDE-209 could be degraded by white rot fungi, and Tween 80 and beta-cyclodextrin can both increase the biodegradation. The best result in Tween 80 experiments was obtained at a Tween 80 concentration of 500mgl(-1) within 10d, which showed 96.5% (w/w) BDE-209 transformed. Tween 80 at a high concentration will restrain the fungal growth and the degradation of BDE-209. However, beta-cyclodextrin had positive effects both on the BDE-209 degradation and the fungal growth. PMID:17707457

  12. Enhanced bioavailability of raloxifene hydrochloride via dry suspensions prepared from drug/HP-β-cyclodextrin inclusion complexes.

    PubMed

    Lu, Rong; Liu, Shan; Wang, Qilin; Li, Xia

    2015-12-01

    This study aimed to develop a dry suspension formulation of raloxifene (RLX) using its HP-β-cyclodextrin inclusion complexes to enhance the oral bioavailability. Dry suspensions loading RLX/HP-β-cyclodextrin inclusion complexes (RLX-HICs) were prepared by solvent evaporation followed by a standard wet granulation process. The inclusion complexes were characterized by scanning electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy. The features of dry suspensions such as dispersibility, flowability and dissolution were compared with conventional suspensions. Dry suspensions containing RLX-HICs dramatically increased the dissolution of RLX. Pharmacokinetic studies in rats showed that dry suspensions with RLX-HICs significantly enhanced the oral bioavailabilities of RLX. The absolute and relative bioavailabilities were up to 13.04% and 413.97% compared with the solution formulation (i.v.) and conventional suspensions (i.g.), respectively. The bioavailability improvement for dry suspensions with RLX-HICs can be attributed to improved dissolution and physiochemical properties of RLX, by which the overall absorption was enhanced. Dry suspensions prepared from RLX-HICs may be an attractive formulation for the oral delivery of RLX. PMID:26817276

  13. Experimental and molecular docking investigations on the inclusion mechanism of the complex of phloridzin and hydroxypropyl-β-cyclodextrin.

    PubMed

    Zhang, Chun-Ling; Liu, Jie-Chao; Yang, Wen-Bo; Chen, Da-Lei; Jiao, Zhong-Gao

    2017-01-15

    Phloridzin is a nutraceutical. Its use in food, medicine and cosmetics is limited because of its low aqueous solubility and stability limits, but it can be improved by complexing with cyclodextrins. In this study, we investigated the inclusion mechanism between phloridzin and hydroxylpropyl-β-cyclodextrin (HP-β-CD) using isothermal titration calorimetry (ITC), ultraviolet-visible spectrometry (UV), infrared spectrometry (IR), proton nuclear magnetic resonance spectroscopy ((1)H NMR) and molecular docking simulations. The ITC results found that the equilibrium binding constant of HP-β-CD with phloridzin was higher than that of β-CD. Their inclusion was a spontaneous process with negative ΔG, ΔH and ΔS values. UV spectra showed that the aqueous solubility of phloridzin was enhanced by HP-β-CD. Our IR analysis verified the inclusion complexation of phloridzin into the HP-β-CD cavity. The Autodock determined that the substitution distribution of HP-β-CD influenced not only the orientation and depth degree of phloridzin within the cavity, but also the binding energies. PMID:27542458

  14. Inclusion complex of ellagic acid with β-cyclodextrin: Characterization and in vitro anti-inflammatory evaluation

    NASA Astrophysics Data System (ADS)

    Bulani, Vipin D.; Kothavade, Pankaj S.; Kundaikar, Harish S.; Gawali, Nitin B.; Chowdhury, Amrita A.; Degani, Mariam S.; Juvekar, Archana R.

    2016-02-01

    Freeze-dried inclusion complex of ellagic acid/β-cyclodextrin (EACD) was investigated both in solution and solid state by means of aqueous solubility, in vitro dissolution, absorption, fluorescence, Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), scanning electron microscopy (SEM), nuclear magnetic resonance (NMR) and molecular modeling methods. The phase solubility study showed that ellagic acid formed 1:2 stoichiometric inclusion complex with β-cyclodextrin (β-CD). The FTIR study indicates that carbonyl group of ellagic acid interact with β-CD. The NMR results demonstrate that ellagic acid was partly included into the β-CD from the wider side of the cavity. Molecular modeling studies revealed that hydrogen bonding interactions played an important role in the inclusion process and higher negative values for the complexation energies imply that 1:2 complex was more stable than 1:1 complex. The solubility and in vitro dissolution of ellagic acid was significantly enhanced by complexation with β-CD as compared to the free ellagic acid. Additionally, the complexation of EACD positively influences it's in vitro anti-inflammatory activity by protecting from protein denaturation and lysis of erythrocyte membrane.

  15. Investigation of inclusion complexes of sulfamerazine with α- and β-cyclodextrins: an experimental and theoretical study.

    PubMed

    Rajendiran, N; Mohandoss, T; Venkatesh, G

    2014-04-24

    Inclusion complexation behavior and binding ability of sulfamerazine (SMRZ) with α- and β-cyclodextrins (α-CD and β-CD) were investigated. The formation of inclusion complexes are studied by UV-visible, fluorescence, time-resolved fluorescence, (1)H NMR, FT-IR, DSC, XRD, SEM, TEM and molecular modeling methods. Both experimental and PM3 results indicated that the SMRZ is partially encapsulated in the CD cavity. The different spectral shifts observed in both the CDs indicate that different types of inclusion complexes are formed. Nanosecond time-resolved fluorescence studies demonstrated that SMRZ exhibit biexponential decay in water and triexponential decay in CD solutions. The resonance of the aromatic protons of SMRZ showed remarkably upfield shift in the complexes suggested that the aniline ring deeply encapsulated in the CD cavity. The amino and amido stretching vibrations at 3483 cm(-1) and 3379 cm(-1) respectively are strongly affected in the inclusion complexes. DSC curves for the inclusion complexes exhibited a broad endothermic effect from 106.4 °C, 123.8 °C and 234.5 6 °C for α-CD and 118.2 °C and 231.4 °C for β-CD. TEM images of both inclusion complexes are forms a nanochain like agglomerated structures with a width ranging from 40 nm to 100 nm. Thermodynamic parameters and binding affinity of the inclusion complex formation were determined and discussed. PMID:24508883

  16. Effect of the simultaneous addition of beta-cyclodextrin and the herbicide norflurazon on its adsorption and movement in soils.

    PubMed

    Villaverde, Jaime; Maqueda, Celia; Morillo, Esmeralda

    2006-06-28

    The effects of beta-cyclodextrin (BCD) on the sorption-desorption and transport processes of the herbicide norflurazon (NFL) in soils of different characteristics when both are applied simultaneously have been investigated. Adsorption-desorption studies of NFL on six soils of very different characteristics in the presence of BCD have been performed using a batch equilibration method and correlated to its mobility in homogeneous hand-packed soil columns. NFL determinations were undertaken by HPLC equipped with a diode array detector at a wavelength of 220 nm. BCD was also analyzed by HPLC with fluorimetric detection using a postcolumn reaction. The interaction of NFL with BCD yielded the formation of an inclusion complex in solution. When this complex is applied to soils, a large decrease in NFL adsorption capacity and an increase in its desorption were observed, due to the higher tendency of NFL-BCD complexes to remain in solution. The results obtained in adsorption and soil column experiments indicated that the influence of BCD on NFL mobility and availability depends on the different affinities of BCD to be sorbed on soils of different characteristics and on the concentration of BCD used. The lower the concentration of BCD added, the more tenaciously it adheres to the soil, and most of the BCD molecules would be adsorbed, providing a coating to soil particles that acts as a bridge between NFL and the soil surface, acting as an adsorbent and retarding the mobility of the herbicide. At higher concentrations of BCD, or in soils where its adsorption is very low, most of the BCD molecules are in the aqueous phase and NFL molecules tend to be complexed with BCD in solution, acting then as a solubilizing agent. PMID:16787026

  17. Effect of inclusion complexation on the photophysical behavior of diphenylamine in β-cyclodextrin medium: A study by electronic spectra

    NASA Astrophysics Data System (ADS)

    Rajamohan, Rajaram; Swaminathan, Meenakshisundaram

    2011-12-01

    Spectral characteristics of diphenylamine (DPA) have been investigated in β-cyclodextrin (β-CDx) solution. The formation of the complex was revealed by UV, steady state and time-resolved fluorescence spectroscopy. The stoichiometry of DPA:β-CDx complex, determined using Benesi-Hildebrand equation and Job's continuous variation method is 1:1. The binding constants calculated from various methods are reported. This inclusion complex formation from DPA and β-CDx was also confirmed by the FT-IR spectral study and SEM image analysis of solid complex prepared by co-precipitation method.

  18. Cyclodextrin supramolecular inclusion-enhanced pyrene excimer switching for time-resolved fluorescence detection of biothiols in serum.

    PubMed

    Zhang, Qier; Deng, Ting; Li, Jishan; Xu, Weijian; Shen, Guoli; Yu, Ruqin

    2015-06-15

    We report here an efficient pyrene excimer signaling-based time-resolved fluorescent sensor for the measurement of biothiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH)) in human serum based on thymine-Hg(2+)-thymine (T-Hg(2+)-T) coordination chemistry and the inclusion interaction of cyclodextrin. The sensing mechanism of the approach is based on the competitive ligation of Hg(2+) ions by Hcy/Cys/GSH and T-T mismatches in a bis-pyrene-labeled DNA strand with the self-complementary 5' and 3' ends. The introduction of γ-cyclodextrin can provide cooperation for the molecular level space proximity of the two labeled pyrene molecules, moreover the hydrophobic cavity of γ-cyclodextrin can also offer protection for the pyrene dimer's emission from the quenching effect of environmental conditions and enhance the fluorescence intensity of the pyrene excimer. When the biothiols are not presented, the sensing ensemble is in the "off" state due to the long distance between the two labeled pyrene molecules resulted from the formation of a more stable T-Hg(2+)-T structure. While in the presence of biothiols, Hg(2+) interacts very strongly with thiol groups and the T-Hg(2+)-T structure is dehybridized, and then the pyrene excimer will be formed due to the self-complementary 5' and 3' ends of the DNA probe and the cooperation interaction of γ-cyclodextrin to pyrene dimer, thus resulting in switching the sensing ensemble to the "on" state. In the optimum conditions described, the linear concentration range of 1.0-100 μM with the limit of detection (LOD) of 0.36 μM for GSH was obtained. Moreover, due to the much longer lifetime of the pyrene excimer fluorescence than those of the ubiquitous endogenous fluorescent components, the time-resolved fluorescence technique has been successfully used for application in complicated biological samples. PMID:25590970

  19. Effects of Two Surfactants and Beta-Cyclodextrin on Beta-Cypermethrin Degradation by Bacillus licheniformis B-1.

    PubMed

    Zhao, Jiayuan; Chi, Yuanlong; Liu, Fangfang; Jia, Dongying; Yao, Kai

    2015-12-23

    The biodegradation efficiency of beta-cypermethrin (β-CY) is low especially at high concentrations mainly due to poor contact between this hydrophobic pesticide and microbial cells. In this study, the effects of two biodegradable surfactants (Tween-80 and Brij-35) and β-cyclodextrin (β-CD) on the growth and cell surface hydrophobicity (CSH) of Bacillus licheniformis B-1 were studied. Furthermore, their effects on the solubility, biosorption, and degradation of β-CY were investigated. The results showed that Tween-80 could slightly promote the growth of the strain while Brij-35 and β-CD exhibited little effect on its growth. The CSH of strain B-1 and the solubility of β-CY were obviously changed by using Tween-80 and Brij-35. The surfactants and β-CD could enhance β-CY biosorption and degradation by the strain, and the highest degradation was obtained in the presence of Brij-35. When the surfactant or β-CD concentration was 2.4 g/L, the degradation rate of β-CY in Brij-35, Tween-80, and β-CD treatments was 89.4%, 50.5%, and 48.1%, respectively. The half-life of β-CY by using Brij-35 was shortened by 69.1 h. Beta-CY content in the soil with both strain B-1 and Brij-35 decreased from 22.29 mg/kg to 4.41 mg/kg after incubation for 22 d. This work can provide a promising approach for the efficient degradation of pyrethroid pesticides by microorganisms. PMID:26615963

  20. The enhancement of fluorescence quantum yields of anilino naphthalene sulfonic acids by inclusion of various cyclodextrins and cucurbit[7]uril

    NASA Astrophysics Data System (ADS)

    Sueishi, Yoshimi; Fujita, Tomonori; Nakatani, Shinichiro; Inazumi, Naoya; Osawa, Yoshihiro

    2013-10-01

    The association constants (K) for the inclusion complexation of four kinds of cyclodextrins (CDs (β- and γ-), 2,6-di-O-methylated β-CD, and 2,3,6-tri-O-methylated β-CD) and cucurbit[7]uril (CB[7]) with 1,8- and 2,6-anilinonaphthalene sulfonic acids (ANSs) were determined from fluorescence spectra enhanced by inclusion. Various CDs and CB[7] form stable 1:1 inclusion complexes with 1,8- and 2,6-ANSs: K = 80-11 700 M-1 for 2,6-ANS and 50-195 M-1 for 1,8-ANS. The high stability of the inclusion complexes of 2,6-ANS with CB[7] and 2,6-di-O-methylated β-CD is shown. Further, we determined the fluorescence quantum yields (Φ values) for the inclusion complexes of ANSs by using a fluorescence spectrophotometer equipped with a half-moon unit. The Φ values of 1,8- and 2,6-ANSs were largely enhanced by the inclusion of methylated β-CDs and did not correlate with the degree of stability (K) of the inclusion complexes. We characterized the structures of the inclusion complexes by 2D ROESY-NMR measurements. In addition, the microenvironmental polarity inside the hydrophobic CD and CB[7] cavities was evaluated using the fluorescence probe 2,6-ANS. Based on the emission mechanism and the aspect of inclusion in a hydrophobic cavity, we have suggested that the microenvironmental polarity and viscosity for the excited state of ANS plays an important role for the Φ values of inclusion complexes.

  1. Inclusion complexes of HP-β-cyclodextrin with agomelatine: Preparation, characterization, mechanism study and in vivo evaluation.

    PubMed

    Liao, Yunhui; Zhang, Xuefei; Li, Chenglin; Huang, Yanjuan; Lei, Ming; Yan, Mina; Zhou, Yuefang; Zhao, Chunshun

    2016-08-20

    Agomelatine (AGM), is efficacious in both the acute phase and the continuation phase of depression. However, its poor water-solubility, low bioavailability and polymorphism limit its pharmacological effects. To address these problems, agomelatine-hydroxypropyl-β-cyclodextrin inclusion complex (AGM/HPβ-CD) was prepared successfully by freeze-drying. The products was evaluated by structural characterization, solubilization test, in-situ absorption of rat intestinal tract and pharmacokinetic study. In addition, thermodynamic studies were performed, the results indicated that the inclusion process was enthalpy-determined and exothermic nature of complexation, signifying the role of steric interactions in complex formation. Molecular docking of AGM with HPβ-CD has been conducted as well to verify the experimental findings and predict the stable molecular structure of the inclusion complex. The in vivo data showed that, AGM was mainly absorbed in duodenum and jejunum by passive diffusion. AGM/HPβ-CD inclusion complex displayed earlier Tmax and higher Cmax, and the AUC0-12h was approximately twice larger than its physical mixture. These results suggested that AGM/HPβ-CD inclusion complex was established with 1:1 stoichiometry through the naphthalene group of AGM and it was deeply inserted into the cavity of HPβ-CD, and the inclusion complex could significantly enhance the oral bioavailability of AGM. PMID:27178948

  2. Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats

    PubMed Central

    Uchida, Ryota; Iwamoto, Kosuke; Nagayama, Suetada; Miyajima, Atsushi; Okamoto, Hinako; Ikuta, Naoko; Fukumi, Hiroshi; Terao, Keiji; Hirota, Takashi

    2015-01-01

    R-α-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of RLA with α-, β- or γ-cyclodextrins (CD) were prepared and orally administered as a suspension to rats. Among them, RLA/γ-CD showed the highest plasma exposure, and its area under the plasma concentration-time curve (AUC) of RLA was 2.2 times higher than that after oral administration of non-inclusion RLA. On the other hand, the AUC after oral administration of non-inclusion RLA and RLA/γ-CD to pylorus-ligated rats did not differ. However, the AUC after intraduodenal administration of RLA/γ-CD was 5.1 times higher than that of non-inclusion RLA, and was almost comparable to the AUC after intraduodenal administration of RLA-Na solution. Furthermore, the AUC after intraduodenal administration of RLA/γ-CD was not affected by biliary ligation or co-administration of an amylase inhibitor. These findings demonstrated that RLA was absorbed from the small intestine effectively when orally administered as a γ-CD inclusion complex, which could be easily dissolved in the lumen of the intestine. In conclusion, γ-CD inclusion complex is an appropriate formulation for supplying RLA as a drug or nutritional supplement with respect to absorption. PMID:25946345

  3. Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium

    PubMed Central

    Nociari, Marcelo M.; Lehmann, Guillermo L.; Perez Bay, Andres E.; Radu, Roxana A.; Jiang, Zhichun; Goicochea, Shelby; Schreiner, Ryan; Warren, J. David; Shan, Jufang; Adam de Beaumais, Ségolène; Ménand, Mickaël; Sollogoub, Matthieu; Maxfield, Frederick R.; Rodriguez-Boulan, Enrique

    2014-01-01

    Accumulation of lipofuscin bisretinoids (LBs) in the retinal pigment epithelium (RPE) is the alleged cause of retinal degeneration in genetic blinding diseases (e.g., Stargardt) and a possible etiological agent for age-related macular degeneration. Currently, there are no approved treatments for these diseases; hence, agents that efficiently remove LBs from RPE would be valuable therapeutic candidates. Here, we show that beta cyclodextrins (β-CDs) bind LBs and protect them against oxidation. Computer modeling and biochemical data are consistent with the encapsulation of the retinoid arms of LBs within the hydrophobic cavity of β-CD. Importantly, β-CD treatment reduced by 73% and 48% the LB content of RPE cell cultures and of eyecups obtained from Abca4-Rdh8 double knock-out (DKO) mice, respectively. Furthermore, intravitreal administration of β-CDs reduced significantly the content of bisretinoids in the RPE of DKO animals. Thus, our results demonstrate the effectiveness of β-CDs to complex and remove LB deposits from RPE cells and provide crucial data to develop novel prophylactic approaches for retinal disorders elicited by LBs. PMID:24706818

  4. Sorption of agrochemical model compounds by sorbent materials containing beta-cyclodextrin.

    PubMed

    Wilson, Lee D; Mohamed, Mohamed H; Guo, Rui; Pratt, Dawn Y; Kwon, Jae Hyuck; Mahmud, Sarker T

    2010-04-01

    Polymeric sorbent materials that incorporate beta-cyclodextrin (CD) have been prepared and their sorption behavior toward two model agrochemical contaminant compounds, p-nitrophenol (PNP) and methyl chloride examined. The sorption of PNP was studied in aqueous solution using ultraviolet-visible (UV-Vis) spectroscopy, whereas the sorption of methyl chloride from the gas phase was studied using a Langmuir adsorption method. The sorption results for PNP in solution were compared between granular activated carbon (GAC), modified GAC, CD copolymers, and CD-based mesoporous silica hybrid materials. Nitrogen porosimetry at 77 K was used to estimate the surface area and pore structure properties of the sorbent materials. The sorbents displayed variable surface areas as follows: copolymers (36.2-157 m(2)/g), CD-silica materials (307-906 m(2)/g), surface modified GAC (657 m(2)/g), and granular activated carbon (approximately 10(3) m(2)/g). The sorption capacities for PNP and methyl chloride with the different sorbents are listed in descending order as follows: GAC > copolymers > surface modified GAC > CD-silica hybrid materials. In general, the differences in the sorption properties of the sorbents were related to the following: (i) surface area of the sorbent, (ii) CD content and accessibility, (iii) and the chemical nature of the sorbent material. PMID:20407992

  5. Cleaning efficacy of hydroxypropyl-beta-cyclodextrin for biofouling reduction on reverse osmosis membranes.

    PubMed

    Alayande, Abayomi Babatunde; Kim, Lan Hee; Kim, In S

    2016-01-01

    In this study, an environmentally friendly compound, hydroxypropyl-beta-cyclodextrin (HP-β-CD) was applied to clean reverse osmosis (RO) membranes fouled by microorganisms. The cleaning with HP-β-CD removed the biofilm and resulted in a flux recovery ratio (FRR) of 102%. As cleaning efficiency is sometimes difficult to determine using flux recovery data alone, attached bacterial cells and extracellular polymeric substances (EPS) were quantified after cleaning the biofouled membrane with HP-β-CD. Membrane surface characterization using scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and atomic force microscopy (AFM) confirmed the effectiveness of HP-β-CD in removal of biofilm from the RO membrane surface. Finally, a comparative study was performed to investigate the competitiveness of HP-β-CD with other known cleaning agents such as sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), Tween 20, rhamnolipid, nisin, and surfactin. In all cases, HP-β-CD was superior. PMID:26923225

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

    NASA Astrophysics Data System (ADS)

    Silva, Nataly; Muñoz, Camila; Diaz-Marcos, Jordi; Samitier, Josep; Yutronic, Nicolás; Kogan, Marcelo J.; Jara, Paul

    2016-04-01

    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).

  7. Enhanced Solubilisation of Six PAHs by Three Synthetic Cyclodextrins for Remediation Applications: Molecular Modelling of the Inclusion Complexes

    PubMed Central

    Morillo, Esmeralda; Sánchez-Trujillo, María Antonia; Moyano, José Ramón; Villaverde, Jaime; Gómez-Pantoja, María Eulalia; Pérez-Martínez, José Ignacio

    2012-01-01

    Solubilisation of six polycyclic aromatic hydrocarbons (PAHs) (acenaphthene, anthracene, fluoranthene, fluorene, phenanthrene and pyrene) by three synthetic cyclodextrins (CDs) (2-hydroxypropyl-β-CD, hydroxypropyl-γ-CD and ramdomly methylated-β-CD) was investigated in order to select the CD which presents the greatest increase in solubility and better complexation parameters for its use in contaminated scenarios. The presence of the three cyclodextrins greatly enhanced the apparent water solubility of all the PAHs through the formation of inclusion complexes of 1∶1 stoichiometry. Anthracene, fluoranthene, fluorene and phenanthrene clearly presented a higher solubility when β-CD derivatives were used, and especially the complexes with the ramdomly methylated-β-CD were favoured. On the contrary, pyrene presented its best solubility results when using 2-hydroxypropyl-γ-CD, but for acenaphthene the use of any of the three CDs gave the same results. Complementary to experimental phase-solubility studies, a more in-depth estimation of the inclusion process for the different complexes was carried out using molecular modelling in order to find a correlation between the degree of solubilisation and the fit of PAH molecules within the cavity of the different CDs and to know the predominant driving forces of the complexation. PMID:23028493

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

    PubMed Central

    Bertaut, Eléonore

    2014-01-01

    Summary 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. PMID:25550724

  9. Spectrofluorimetric estimation of salbutamol sulphate in different dosage forms by formation of inclusion complex with β-cyclodextrin.

    PubMed

    Pandya, Harshit Narmadashankar; Berawala, Hiren Harshadlal; Khatri, Deepak Mohanlal; Mehta, Priti Jignesh

    2010-10-01

    A simple, precise, reproducible and accurate spectrofluorimetric method for estimation of Salbutamol sulphate (SAL) in bulk drug and various dosage forms has been developed. This method is based on formation of inclusion complex of SAL in β-cyclodextrin (BCD) which gives fluorescence at excitation wavelength of 279.6 nm and emission wavelength of 609.8 nm in water. Formation of inclusion complex of drug with BCD enhances fluorescence intensity of drug leads to increased sensitivity. The developed method was validated according to ICH guidelines with respect to accuracy, precision, linearity, limit of detection, limit of quantification. Linearity was observed in the range of 4-20 μg/ml with correlation coefficient of 0.9982. The simplicity of the method permitted rapid analysis suitable for routine control. The developed method was successfully applied for the estimation of SAL in different marketed dosage forms like tablets, syrup and aerosol. PMID:23781416

  10. The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes

    PubMed Central

    Ye, Ya-Jing; Wang, Yun; Lou, Kai-Yan; Chen, Yan-Zuo; Chen, Rongjun; Gao, Feng

    2015-01-01

    A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9–407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9–23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol®), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC0→24h (the area under the plasma drug concentration–time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects. PMID:26170666

  11. The preparation, characterization, and pharmacokinetic studies of chitosan nanoparticles loaded with paclitaxel/dimethyl-β-cyclodextrin inclusion complexes.

    PubMed

    Ye, Ya-Jing; Wang, Yun; Lou, Kai-Yan; Chen, Yan-Zuo; Chen, Rongjun; Gao, Feng

    2015-01-01

    A novel biocompatible and biodegradable drug-delivery nanoparticle (NP) has been developed to minimize the severe side effects of the poorly water-soluble anticancer drug paclitaxel (PTX) for clinical use. PTX was loaded into the hydrophobic cavity of a hydrophilic cyclodextrin derivative, heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), using an aqueous solution-stirring method followed by lyophilization. The resulting PTX/DM-β-CD inclusion complex dramatically enhanced the solubility of PTX in water and was directly incorporated into chitosan (CS) to form NPs (with a size of 323.9-407.8 nm in diameter) using an ionic gelation method. The formed NPs had a zeta potential of +15.9-23.3 mV and showed high colloidal stability. With the same weight ratio of PTX to CS of 0.7, the loading efficiency of the PTX/DM-β-CD inclusion complex-loaded CS NPs was 30.3-fold higher than that of the PTX-loaded CS NPs. Moreover, it is notable that PTX was released from the DM-β-CD/CS NPs in a sustained-release manner. The pharmacokinetic studies revealed that, compared with reference formulation (Taxol(®)), the PTX/DM-β-CD inclusion complex-loaded CS NPs exhibited a significant increase in AUC(0→24h) (the area under the plasma drug concentration-time curve over the period of 24 hours) and mean residence time by 2.7-fold and 1.4-fold, respectively. Therefore, the novel drug/DM-β-CD inclusion complex-loaded CS NPs have promising applications for the significantly improved delivery and controlled release of the poorly water-soluble drug PTX or its derivatives, thus possibly leading to enhanced therapeutic efficacy and less severe side effects. PMID:26170666

  12. Host-guest inclusion system of oleanolic acid with methyl-β-cyclodextrin: Preparation, characterization and anticancer activity

    NASA Astrophysics Data System (ADS)

    Ren, Yufeng; Liu, Ying; Niu, Raomei; Liao, Xiali; Zhang, Jihong; Yang, Bo

    2016-08-01

    In this study, the solid inclusion complex of oleanolic acid (OA) with methyl-β-cyclodextrin (M-β-CD) was prepared and characterized by nuclear magnetic resonance (NMR), X-ray diffraction (XRD), scanning electron microscope (SEM) and differential scanning calorimetry (DSC). The inclusion behaviors of OA/M-β-CD complex were studied by fluorescence spectroscopy and the Job plot, which indicated a 1:1 inclusion mode between OA and M-β-CD. The stability constant (Ks) of the complex was 1072.30 ± 20 M-1 determined by spectral titration at 25 °C. Besides, the water solubility of OA was significantly increased to 8.2 mg/mL by inclusion complexation, compared to only ca. 0.012 μg/mL of free OA. The in vitro cytotoxicity of the inclusion complex was noticeably better than that of native OA with the IC50 values of 8.89, 7.89 and 5.77 μM on human cancer cell lines HepG2, HT29 and HCT116, respectively, by MTT assay.

  13. Preparation and characterization of inclusion complex of benzyl isothiocyanate extracted from papaya seed with β-cyclodextrin.

    PubMed

    Li, Wenzhao; Liu, Xiaoyu; Yang, Qingfeng; Zhang, Ning; Du, Yideng; Zhu, Huaping

    2015-10-01

    The inclusion complex of benzyl isothiocyanate (BITC), extracted from papaya seed with β-cyclodextrin (β-CD), was prepared. Different analytical techniques, such as Fourier transform infrared spectroscopy, thermal analysis, X-ray diffractometry, particle size distribution analysis and (1)H Nuclear magnetic resonance analysis, were used to investigate the characterization of the inclusion complex (BITC-β-CD). All these approaches indicated that the inclusion complex was capable of being formed. The inclusion complex exhibited different spectroscopic and thermodynamic features and properties from BITC, and we deduced the possible inclusion modes for BITC-β-CD. The calculated apparent stability constant of the BITC-β-CD was 600.8l/mol, and the aqueous solubility of BITC was indistinctively improved by phase solubility studies. The results illustrated that β-CD was a proper excipient for increasing the stability and controlled release of BITC. Thus, β-CD complexation technology would be a promising approach, in expanding the application of BITC as a food antibacterial agent. PMID:25872431

  14. Inclusion Complex of Novel Curcumin Analogue CDF and β-Cyclodextrin (1:2) and Its Enhanced In Vivo Anticancer Activity Against Pancreatic Cancer

    PubMed Central

    Dandawate, Prasad R.; Vyas, Alok; Ahmad, Aamir; Banerjee, Sanjeev; Deshpande, Jyoti; Swamy, K. Venkateswara; Jamadar, Abeda; Dumhe-Klaire, Anne Catherine

    2013-01-01

    Purpose Several formulations have been proposed to improve the systemic delivery of novel cancer therapeutic compounds, including cyclodextrin derivatives. We aimed to synthesize and characterize of CDF-β-cyclodextrin inclusion complex (1:2) (CDFCD). Methods The compound was characterized by Fourier transform infrared, differential scanning calorimetry, powder X-ray diffraction studies, H1 & C13 NMR studies and scanning electron microscopic analysis. Its activity was tested against multiple cancer cell lines, and in vivo bioavailability was checked. Results CDF-β-cyclodextrin was found to lower IC50 value by half when tested against multiple cancer cell lines. It preferentially accumulated in the pancreas, where levels of CDF-β-cyclodextrin in mice were 10 times higher than in serum, following intravenous administration of an aqueous CDF-β-cyclodextrin preparation. Conclusions Novel curcumin analog CDF preferentially accumulates in the pancreas, leading to its potent anticancer activity against pancreatic cancer cells. Synthesis of such CDF-β-cyclodextrin self-assembly is an effective strategy to enhance its bioavailability and tissue distribution, warranting further evaluation for CDF delivery in clinical settings for treatment of human malignancies. PMID:22322899

  15. High-resolution solid-state 13C CP MAS NMR spectra of some β-cyclodextrin inclusion complexes with nitriles

    NASA Astrophysics Data System (ADS)

    Okazaki, M.; McDowell, C. A.

    1983-11-01

    β-cyclodextrin inclusion complexes of 3-aminobenzonitrile, 4-aminobenzonitrile, and adamantane-1-carbonitrile were studied by means of high-resolution solid-state CP MAS 13C NMR spectroscopy. The interactions between the host and guest molecules are discussed.

  16. Inclusion complexes of 2-methoxyestradiol with dimethylated and permethylated β-cyclodextrins: models for cyclodextrin–steroid interaction

    PubMed Central

    Bourne, Susan A; Samsodien, Halima; Smith, Vincent J

    2015-01-01

    Summary The interaction between the potent anticancer agent 2-methoxyestradiol (2ME) and a series of cyclodextrins (CDs) was investigated in the solid state using thermal analysis and X-ray diffraction, while the possibility of enhancing its poor aqueous solubility with CDs was probed by means of equilibrium solubility and dissolution rate measurements. Single crystal X-ray diffraction studies of the inclusion complexes between 2ME and the derivatised cyclodextrins heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) revealed for the first time the nature of the encapsulation of a bioactive steroid by representative CD host molecules. Inclusion complexation invariably involves insertion of the D-ring of 2ME from the secondary side of each CD molecule, with the 17-OH group generally hydrogen bonding to a host glycosidic oxygen atom within the CD cavity, while the A-ring and part of the B-ring of 2ME protrude from the secondary side. In the case of the TRIMEB·2ME complex, there is evidence that complexation proceeds with mutual conformational adaptation of host and guest molecules. The aqueous solubility of 2ME was significantly enhanced by CDs, with DIMEB, TRIMEB, randomly methylated β-CD and hydroxypropyl-β-CD being the most effective hosts. The 2:1 host–guest β-CD inclusion complex, prepared by two methods, yielded very rapid dissolution in water at 37 °C relative to untreated 2ME, attaining complete dissolution within 15 minutes (co-precipitated complex) and 45 minutes (complex from kneading). PMID:26734107

  17. Inclusion interaction of chloramphenicol and heptakis (2,6-di- O-methyl)-β-cyclodextrin: Phase solubility and spectroscopic methods

    NASA Astrophysics Data System (ADS)

    Shi, Jie-Hua; Zhou, Ya-fang

    2011-12-01

    The inclusion interaction between chloramphenicol and heptakis (2,6-di- O-methyl)-β-cyclodextrin (DMBCD) had been investigated by phase solubility and spectroscopic methods such as UV-vis spectroscopy, circular dichroism, Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance spectroscopy ( 1H NMR) as well as 2D-ROESY spectra. Phase solubility analysis showed A L-type diagram with DMBCD, which suggested the formation of 1:1 inclusion complex of DMBCD with chloramphenicol. The estimated stability constant ( Ks) of the inclusion complex of chloramphenicol with DMBCD is 493 M -1 at 293 K. The solubility enhancement of chloramphenicol in the presence of DMBCD is stronger than that in the presence of β-CD, HP-β-CD and M-β-CD. The results obtained by spectroscopic methods showed that the nitrophenyl moiety of chloramphenicol is deeply inserted into inner cavity of DMBCD from the narrow rim of DMBCD, which the inclusion model of chloramphenicol with DMBCD differs from that with β-CD.

  18. Interaction Mode between Inclusion Complex of Vitamin K3 with γ- Cyclodextrin and Herring-Sperm DNA.

    PubMed

    Tang, Yan; Cai, Li; Xue, Kang; Wang, Chunling; Xiong, Xiaoli

    2016-05-01

    Methods including spectroscopy, electronic chemistry and thermodynamics were used to study the inclusion effect between γ-cyclodextrin (CD) and vitamin K3(K3), as well as the interaction mode between herring-sperm DNA (hsDNA) and γ-CD-K3 inclusion complex. The results from ultraviolet spectroscopic method indicated that VK3 and γ-CD formed 1:1 inclusion complex, with the inclusion constant Kf = 1.02 × 10(4) L/mol, which is based on Benesi-Hildebrand's viewpoint. The outcomes from the probe method and Scatchard methods suggested that the interaction mode between γ-CD-K3 and DNA was a mixture mode, which included intercalation and electrostatic binding effects. The binding constants were K (θ)25°C = 2.16 × 10(4) L/mol, and K(θ)37°C = 1.06 × 10(4) L/mol. The thermodynamic functions of the interaction between γ-CD-K3 and DNA were ΔrHm(θ) = -2.74 × 10(4) J/mol, ΔrSm(θ) = 174.74 J·mol(-1)K(-1), therefore, both ΔrHm(θ) (enthalpy) and ΔrSm(θ) (entropy) worked as driven forces in this action. PMID:27057789

  19. Facile synthesis of mono-6-amino-6-deoxy-alpha-, beta-, gamma-cyclodextrin hydrochlorides for molecular recognition, chiral separation and drug delivery.

    PubMed

    Tang, Weihua; Ng, Siu-Choon

    2008-01-01

    We describe a protocol for the synthesis of mono-6-amino-6-deoxy-cyclodextrin hydrochloride (CD-NH3Cl), applicable to alpha-, beta- and gamma-cyclodextrin. These structurally simplest, highly water-soluble cationic cyclodextrins can be widely used in molecular recognition, chiral separation and drug delivery studies. Starting from commercially available chemicals, CD-NH3Cl is synthesized in four steps: (i) selective tosylation of cyclodextrin by the use of p-toluenesulfonyl chloride to afford mono-6-(p-toluenesulfonyl)-6-deoxy-cyclodextrin (Ts-CD); (ii) azide substitution of Ts-CD with sodium azide to afford mono-6-azido-6-deoxy-cyclodextrin (CD-N3); (iii) reduction of CD-N3 with triphenylphospine followed by hydrolysis to prepare mono-6-amino-6-deoxy-cyclodextrin (CD-NH2); and (iv) treatment of CD-NH2 with hydrochloric acid to afford the titled CD-NH3Cl with good yield. The overall protocol requires approximately 2 weeks. PMID:18388952

  20. Physical-chemical characterization of binary systems of metformin hydrochloride with triacetyl-beta-cyclodextrin.

    PubMed

    Corti, Giovanna; Capasso, Gaetano; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

    2007-11-01

    Interaction products of metformin hydrochloride (MF.HCl), an oral anti-hyperglycaemic agent highly soluble in water, with triacetyl-beta-cyclodextrin (TAbetaCyD), a hydrophobic CyD derivative practically insoluble in water, were prepared to evaluate their suitability for the development of a sustained-release dosage form of the drug. Equimolar MF.HCl-TAbetaCyD solid compounds were obtained by different techniques, i.e., physical mixing, kneading, co-grinding, sealed-heating, and spray-drying, in order to investigate and compare their effectiveness and influence on the physical-chemical properties of the final products. Differential scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used for the solid-state characterization of the different MF.HCl-TAbetaCyD systems, whereas their in vitro dissolution properties were determined according to the dispersed amount method. According to the results of solid-state studies, the ability of the different preparation methods to promote effective interactions between drug and CyD varied in the order: spray-drying>co-grinding>kneading>sealed-heating approximately physical mixing. The same effectiveness rank order was observed also in dissolution studies. In fact the time to dissolve 100% drug varied increased from 1 min, for pure drug, to 3, 7, 40, 120 up to 420 min for physically mixed, sealed-heated, kneaded, co-ground and spray-dried products, respectively. Thus the drug-TA(CyD products obtained by spray drying and co-grinding were selected as the best candidates for the future development of a suitable prolonged-release oral dosage form of MF.HCl. PMID:17822867

  1. Sustained-release matrix tablets of metformin hydrochloride in combination with triacetyl-beta-cyclodextrin.

    PubMed

    Corti, Giovanna; Cirri, Marzia; Maestrelli, Francesca; Mennini, Natascia; Mura, Paola

    2008-02-01

    The low bioavailability and short half-life of metformin hydrochloride (MH) make the development of sustained-release forms desirable. However, drug absorption is limited to the upper gastrointestinal (GI) tract, thus requiring suitable delivery systems providing complete release during stomach-to-jejunum transit. This study was undertaken to develop a MH sustained-release formulation in compliance with these requirements. The strategy proposed is based on direct-compressed matrix tablets consisting of a combination of MH with the hydrophobic triacetyl-beta-cyclodextrin (TAbetaCD), dispersed in a polymeric material. Different polymers were tested as excipients, i.e. hydroxypropylmethylcellulose, xanthan gum, chitosan, ethylcellulose, Eudragit L100-55, and Precirol. Compatibility among the formulation components was assessed by DSC analysis. All the tablets were examined for drug release pattern in simulated gastric and jejunal fluids used in sequence to mimic the GI transit. Release studies demonstrated that blends of a hydrophobic swelling polymer (hydroxypropylmethylcellulose or chitosan) with a pH-dependent one (Eudragit L100-55) were more useful than single polymers in controlling drug release. Moreover, the main role played by the MH-TAbetaCD system preparation method (i.e. grinding or spray-drying) in determining the behaviour of the final formulation was evidenced. In fact, for a given matrix-tablet composition, different sustained-release effects were obtained by varying the relative amounts of MH-TAbetaCD as ground or spray-dried product. In particular, the 1:1 (w/w) blend of such systems, dispersed in a Eudragit-chitosan polymeric matrix, fully achieved the prefixed goal, giving about 30% released drug after 2h at gastric pH, and overcoming 90% released drug within the subsequent 3h in jejunal fluid. PMID:17616379

  2. Improved aqueous solubility of crystalline astaxanthin (3,3'-dihydroxy-beta, beta-carotene-4,4'-dione) by Captisol (sulfobutyl ether beta-cyclodextrin).

    PubMed

    Lockwood, Samuel F; O'Malley, Sean; Mosher, Gerold L

    2003-04-01

    Carotenoids are the most widely distributed natural pigments, with over 600 individual compounds identified and characterized from natural sources. A few are commercially important molecules, having found utility as additions to animal feed in the aquaculture, poultry, and swine feed industries. The majority are lipophilic molecules with near zero inherent aqueous solubility. Many different methods have been developed to make the carotenoids "water dispersible," as true water solubility has not been described. Astaxanthin (3,3'-dihydroxy-beta, beta-carotene-4,4'-dione) is a commercially important oxygenated carotenoid that has gained wide acceptance as a feed additive in the $50 billion salmon and trout aquaculture industry. Recently, interest in the human health applications of astaxanthin has increased, with astaxanthin receiving approval as a dietary supplement in several countries, including the United States. Moving astaxanthin into a pharmaceutical application will require a chemical delivery system that overcomes the problems with parenteral administration of a highly lipophilic, low molecular weight compound. In the current study, the ability of sulfobutyl ether beta-cyclodextrin (sodium), as the Captisol(R) brand, to increase the aqueous water solubility of crystalline astaxanthin was evaluated. Complexation of crystalline astaxanthin with Captisol increased the apparent water solubility of crystalline astaxanthin approximately 71-fold, to a concentration in the 2 microg/mL range. It is unlikely that this increase in solubility will result in a pharmaceutically acceptable chemical delivery system for humans. However, the increased aqueous solubility of crystalline astaxanthin to the range achieved in the current study will likely find utility in the introduction of crystalline astaxanthin into mammalian cell culture systems that have previously been dependent upon liposomes, or toxic organic solvents, for the introduction of carotenoids into aqueous

  3. Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process.

    PubMed

    Rudrangi, Shashi Ravi Suman; Kaialy, Waseem; Ghori, Muhammad U; Trivedi, Vivek; Snowden, Martin J; Alexander, Bruce David

    2016-07-01

    The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11±0.09% dissolving at the end of 60min, while the binary mixtures processed by supercritical carbon dioxide at 45°C and 200bar released 99.39±2.34% of the drug at the end of 30min. All the binary mixtures processed by supercritical carbon dioxide at 45°C exhibited a drug release of more than 80% within the first 10min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state. PMID:27163245

  4. Preparation, release and physicochemical characterisation of ethyl butyrate and hexanal inclusion complexes with β- and γ-cyclodextrin.

    PubMed

    Zhang, Yang; Zhou, Yibin; Cao, Shengnan; Li, Songnan; Jin, Shanshan; Zhang, Shu

    2015-01-01

    Complexes of ethyl butyrate and hexanal encapsulated by β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) were prepared by coprecipitation, and gas chromatography was used to quantity the flavour compounds in the complexes. The ethyl butyrate-γ-CD complex had the highest inclusion ratio (12.20%) followed by the ethyl butyrate-β-CD, hexanal-β-CD and hexanal-γ-CD complexes (11.29, 4.41 and 3.33%, respectively). Release experiments were performed under different relative humidities (RH 93, 75 and 52%) and temperatures (4 and 25 °C). The flavour release behaviours of the complexes were described by the Avrami equation. The rate of flavour release was enhanced with both increasing temperature and RH, although the effect of RH was stronger. Physicochemical characterisation using FT-IR, XRD, DSC and SEM analyses demonstrated that crystalline complexes were formed. Both β-CD and γ-CD were able to encapsulate ethyl butyrate and hexanal, and lower RH and temperature were more suitable for the storage of these complexes. PMID:26471403

  5. Improved thermal stability of polylactic acid (PLA) composite film via PLA-β-cyclodextrin-inclusion complex systems.

    PubMed

    Byun, Youngjae; Rodriguez, Katia; Han, Jung H; Kim, Young Teck

    2015-11-01

    The effects of the incorporation of PLA-β-cyclodextrin-inclusion complex (IC) and β-cyclodextrin (β-CD) on biopolyester PLA films were investigated. Thermal stability, surface morphology, barrier, and mechanical properties of the films were measured at varying IC (1, 3, 5, and 7%) and β-CD (1 and 5%) concentrations. The PLA-IC-composite films (IC-PLA-CFs) showed uniform morphological structure, while samples containing β-CD (β-CD-PLA-CFs) showed high agglomeration of β-CD due to poor interfacial interaction between β-CD and PLA moieties. According to the thermal property analysis, the 5% IC-PLA-CFs showed 6.6 times lower dimensional changes (6.5%) at the temperature range of 20-80°C than that of pure PLA film (43.0%). The increase of IC or β-CD content in the PLA-composite films shifted the glass transition and crystallization temperature to higher temperature regions. The crystallinity of both composite films improved by increasing IC or β-CD content. Both composite films had higher oxygen and water vapor permeability as IC or β-CD content increased in comparison to pure PLA film. All the composite films had less flexibility and lower tensile strength than the pure PLA film. In conclusion, this study shows that the IC technique is valuable to improve the thermal expansion stability of PLA-based films. PMID:26299710

  6. Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

    PubMed Central

    Markenstein, Lisa; Appelt-Menzel, Antje; Metzger, Marco

    2014-01-01

    Summary The mono-6-deoxy-6-azides of 2,6-di-O-methyl-β-cyclodextrin (DIMEB) and randomly methylated-β-cyclodextrin (RAMEB) were conjugated to propargylated hydroxyethyl starch (HES) by Cu+-catalysed [2 + 3] cycloaddition. The resulting water soluble polymers showed lower critical solution temperatures (LCST) at 52.5 °C (DIMEB-HES) and 84.5 °C (RAMEB-HES), respectively. LCST phase separations could be completely avoided by the introduction of a small amount of carboxylate groups at the HES backbone. The methylated CDs conjugated to the HES backbone exhibited significantly lower cytotoxicities than the corresponding monomeric CD derivatives. Since the binding potentials of these CD conjugates were very high, they are promising candidates for new oral dosage forms of anaesthetic actives. PMID:25670977

  7. Electronic structure and driving forces in β-cyclodextrin: Diclofenac inclusion complexes

    NASA Astrophysics Data System (ADS)

    Bogdan, Diana; Morari, C.

    2007-07-01

    We investigate the geometry and electronic structure for complexes of β-cyclodextrin with diclofenac using DFT calculations. The effect of solvent is explicitly taken into account. This investigation allows us to draw meaningful conclusions upon the stability of the complex and the nature of the driving forces leading to the complexation process. In particular we emphasize the role of the water, by pointing out the changes in the solvent's electronic structure for different docking geometries.

  8. Computational study on the conformations of CD38 and inclusion complexes of some lower-size large-ring cyclodextrins

    NASA Astrophysics Data System (ADS)

    Ivanov, Petko; Atanassov, Emanouil; Jaime, Carlos

    2014-01-01

    The conformations of CD38 were examined by conformational search with molecular dynamics simulations using the Glycam04 force field. The results were compared with previous ones for CD26, the largest cyclodextrin for which crystal data are available. Principal component analysis (PCA) was applied for post-processing of the simulation trajectories. Limited number of modes determine the overall deformations of the macroring of CD38. The longer perimeter of the macroring allowed the formation of a form not observed so far - a three-turn helix shaped as a short tube. In analogy with CD26, significant participation was monitored for conformations of CD38 with one-turn spirals at the opposite sides of the macroring linked together from the 'bottom' and from the 'top' with extended bridge spacers. Computationally were examined for the first time inclusion complexes of some lower-size LR-CDs, namely complexes of CDn (n = 13, 14, 26) with adamantane and of CD14 with 1-hydroxyadamantane. The macroring conformation of CD13 was not altered by the inclusion of the substrate molecule which acquired preferred positioning not in the middle of the cavity but rather close to the glucose residues at one of the sides. The same positioning of the small molecule in the cavity of the more flexible CD14 macroring enhanced the appearance of bent onto two conformation of this cyclodextrin. The most interesting behaviour presented the complex of CD26 with adamantane in which case the small molecule acts as a 'nucleation center' for the formation of a second helical turn about the substrate molecule.

  9. Inclusion complexation with β-cyclodextrin derivatives alters photodynamic activity and biodistribution of meta-tetra(hydroxyphenyl)chlorin.

    PubMed

    Yankovsky, Igor; Bastien, Estelle; Yakavets, Ilya; Khludeyev, Ivan; Lassalle, Henri-Pierre; Gräfe, Susanna; Bezdetnaya, Lina; Zorin, Vladimir

    2016-08-25

    Application of meta-tetra(hydroxyphenyl)chorin (mTHPC) one of the most effective photosensitizer (PS) in photodynamic therapy of solid tumors encounters several complications resulting from its insolubility in aqueous medium. To improve its solubility and pharmacokinetic properties, two modified β-cyclodextrins (β-CDs) methyl-β-cyclodextrin (M-β-CD) and 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) were proposed. The aim of this work was to evaluate the effect of β-CDs on mTHPC behavior at various stages of its distribution in vitro and in vivo. For this purpose, we have studied the influence of the β-CDs on mTHPC binding to the serum proteins, its accumulation, distribution and photodynamic efficiency in HT29 cells. In addition, the processes of mTHPC biodistribution in HT29 tumor bearing mice after intravenous injection of PS alone or with the β-CDs were compared. Interaction of mTHPC with studied β-CDs leads to the formation of inclusion complexes that completely abolishes its aggregation after introduction into serum. It was demonstrated that the β-CDs have a concentration-dependent effect on the process of mTHPC distribution in blood serum. At high concentrations, β-CDs can form inclusion complexes with mTHPC in the blood that can have a significant impact on PS distribution out of the vascular system in solid tissues. Besides, the β-CDs increase diffusion movement of mTHPC molecules that can significantly accelerate the delivery of PS to the targets cells and tissues. In vivo study confirms the fact that the use of β-CDs allows to modify mTHPC distribution processes in tumor bearing animals that is reflected in the decreased level of PS accumulation in skin and muscles, as well as in the increased PS accumulation in tumor. Further studies are underway to verify the optimal protocols of mTHPC/β-CD formulation for photodynamic therapy. PMID:27320407

  10. Preparation, characterisation and antitumour activity of β-, γ- and HP-β-cyclodextrin inclusion complexes of oxaliplatin

    NASA Astrophysics Data System (ADS)

    Zhang, Da; Zhang, Jianqiang; Jiang, Kunming; Li, Ke; Cong, Yangwei; Pu, Shaoping; Jin, Yi; Lin, Jun

    2016-01-01

    Three water-soluble oxaliplatin complexes were prepared by inclusion complexation with β-cyclodextrin (β-CD), γ-CD and HP-β-CD. The structures of oxaliplatin/CDs were confirmed by NMR, FTIR, TGA, XRD as well as SEM analysis. The results show that the water solubility of oxaliplatin was increased in the complex with CDs in 1:1 stoichiometry inclusion modes, and the cyclohexane ring of oxaliplatin molecule was deeply inserted into the cavity of CDs. Moreover, the stoichiometry was established by a Job plot and the water stability constant (Kc) of oxaliplatin/CDs was calculated by phase solubility studies, all results show that the oxaliplatin/β-CD complex is more stable than free oxaliplatin, oxaliplatin/HP-β-CD and oxaliplatin/γ-CD. Meanwhile, the inclusion complexes displayed almost twice as high cytotoxicity compared to free oxaliplatin against HCT116 and MCF-7 cells. This satisfactory water solubility and higher cytotoxic activity of the oxaliplatin/CD complexes will potentially be useful for their application in anti-tumour therapy.

  11. Host-guest inclusion complex of propafenone hydrochloride with α- and β-cyclodextrins: spectral and molecular modeling studies.

    PubMed

    Siva, S; Thulasidhasan, J; Rajendiran, N

    2013-11-01

    Host-guest inclusion complexes of cyclodextrins (CDs) with a potential cardiovascular drug propafenone hydrochloride (PFO), were prepared and characterized using absorption, fluorescence, time-resolved fluorescence, SEM, FT-IR, DSC, (1)H NMR, XRD and PM3 methods. The spectral studies suggested the phenyl ring along with carbonyl group is present inside of CD cavity. Solvent studies revealed that the normal Stokes shifted band originates from the locally excited state and the large Stokes shifted band occurs due to the emission from ICT. Nanosecond time-resolved studies indicated that PFO exhibits biexponential decay in water and triexponential decay in CD, indicating the formation of 1:1 inclusion complex. The results from solid state studies showed important modifications in the physicochemical properties of free PFO. The ΔH, ΔG and ΔS of the complexation process were determined and it was found that the complexation processes were spontaneous. Investigations of thermodynamic and electronic properties confirmed the stability of the inclusion complex. PMID:23872014

  12. Host-guest inclusion complex of propafenone hydrochloride with α- and β-cyclodextrins: Spectral and molecular modeling studies

    NASA Astrophysics Data System (ADS)

    Siva, S.; Thulasidhasan, J.; Rajendiran, N.

    2013-11-01

    Host-guest inclusion complexes of cyclodextrins (CDs) with a potential cardiovascular drug propafenone hydrochloride (PFO), were prepared and characterized using absorption, fluorescence, time-resolved fluorescence, SEM, FT-IR, DSC, 1H NMR, XRD and PM3 methods. The spectral studies suggested the phenyl ring along with carbonyl group is present inside of CD cavity. Solvent studies revealed that the normal Stokes shifted band originates from the locally excited state and the large Stokes shifted band occurs due to the emission from ICT. Nanosecond time-resolved studies indicated that PFO exhibits biexponential decay in water and triexponential decay in CD, indicating the formation of 1:1 inclusion complex. The results from solid state studies showed important modifications in the physicochemical properties of free PFO. The ΔH, ΔG and ΔS of the complexation process were determined and it was found that the complexation processes were spontaneous. Investigations of thermodynamic and electronic properties confirmed the stability of the inclusion complex.

  13. Molecular modeling-based inclusion mechanism and stability studies of doxycycline and hydroxypropyl-β-cyclodextrin complex for ophthalmic delivery.

    PubMed

    Zhang, Haohao; Chen, Meiwan; He, Zixin; Wang, Zhouhua; Zhang, Meimei; He, Zhouyang; Wan, Qian; Liang, Dan; Repka, Michael A; Wu, Chuanbin

    2013-03-01

    The aim of the present study was to prepare a stable complex of doxycycline (Doxy) and hydroxypropyl-β-cyclodextrin (HPβCD) for ophthalmic delivery and investigate the inclusion mechanism and the inclusion effects on the stability of Doxy. The Doxy/HPβCD complex was prepared by solution stirring and then characterized by scanning electron microscopy and ultraviolet spectroscopy. Based on results of nuclear magnetic resonance, molecular model of Doxy/HPβCD complex was established using computational simulation of PM3 method implemented in Gaussian 03. Stabilities of Doxy/HPβCD complex in both aqueous solution and solid state at 25°C were evaluated by HPLC. Finally, in vitro antibacterial activity of the Doxy/HPβCD complex was evaluated by disk diffusion test. It was found that the stabilities of Doxy/HPβCD complex in both aqueous solution and solid state were improved obviously as compared with Doxy alone. This stability enhancement is consistent with the inclusion mechanism between HPβCD and Doxy, which showed that the unstable site of Doxy molecule at 6-CH3 was protected in the hydrophobic cavity of HPβCD, additionally, the chelation of Mg2+ provided a synergetic protection of the other unstable site of Doxy at 4-N(CH3)2. The antibacterial activity results indicated that Doxy/HPβCD complex might have potential for clinical applications. PMID:23160918

  14. Co-solvation effect on the binding mode of the α-mangostin/β-cyclodextrin inclusion complex

    PubMed Central

    Rungnim, Chompoonut; Phunpee, Sarunya; Kunaseth, Manaschai; Namuangruk, Supawadee; Rungsardthong, Kanin

    2015-01-01

    Summary Cyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents in such studies may result in ternary (host:guest:co-solvent) complex formation. The objective of this work was to investigate the effect of ethanol as a co-solvent on the inclusion complex formation between α-mangostin (α-MGS) and β-CD, using both experimental and theoretical studies. Experimental phase-solubility studies were carried out in order to assess complex formation, with the mechanism of association being probed using a mathematical model. It was found that α-MGS was poorly soluble at low ethanol concentrations (0–10% v/v), but higher concentrations (10–40% v/v) resulted in better α-MGS solubility at all β-CD concentrations studied (0–10 mM). From the equilibrium constant calculation, the inclusion complex is still a binary complex (1:1), even in the presence of ethanol. The results from our theoretical study confirm that the binding mode is binary complex and the presence of ethanol as co-solvent enhances the solubility of α-MGS with some effects on the binding affinity with β-CD, depending on the concentration employed. PMID:26734079

  15. Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

    PubMed Central

    Kfoury, Miriana; Landy, David; Ruellan, Steven; Auezova, Lizette; Greige-Gerges, Hélène

    2016-01-01

    Summary Carvacrol and thymol have been widely studied for their ability to control food spoilage and to extend shelf-life of food products due to their antimicrobial and antioxidant activities. However, they suffer from poor aqueous solubility and pronounced flavoring ability that limit their application in food systems. These drawbacks could be surpassed by encapsulation in cyclodextrins (CDs). Applications of their inclusion complexes with CDs were reported without investigating the inclusion phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (K f), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV–visible competitive method, phase solubility studies as well as 1H and DOSY 1H NMR titration experiments. For the first time, a new algorithmic treatment that combines the chemical shifts and diffusion coefficients variations for all guest protons was applied to calculate K f. The position of the hydroxy group in carvacrol and thymol did not affect the stoichiometry of the inclusion complexes but led to a different binding stability with CDs. 2D ROESY NMR experiments were also performed to prove the encapsulation and illustrate the stable 3D conformation of the inclusion complexes. The structural investigation was accomplished with molecular modeling studies. Finally, the radical scavenging activity of carvacrol and thymol was evaluated by the ABTS radical scavenging assay. An improvement of this activity was observed upon encapsulation. Taken together, these results evidence that the encapsulation in CDs could be valuable for applications of carvacrol and thymol in food. PMID:26877806

  16. Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol.

    PubMed

    Kfoury, Miriana; Landy, David; Ruellan, Steven; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2016-01-01

    Carvacrol and thymol have been widely studied for their ability to control food spoilage and to extend shelf-life of food products due to their antimicrobial and antioxidant activities. However, they suffer from poor aqueous solubility and pronounced flavoring ability that limit their application in food systems. These drawbacks could be surpassed by encapsulation in cyclodextrins (CDs). Applications of their inclusion complexes with CDs were reported without investigating the inclusion phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (K f), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV-visible competitive method, phase solubility studies as well as (1)H and DOSY (1)H NMR titration experiments. For the first time, a new algorithmic treatment that combines the chemical shifts and diffusion coefficients variations for all guest protons was applied to calculate K f. The position of the hydroxy group in carvacrol and thymol did not affect the stoichiometry of the inclusion complexes but led to a different binding stability with CDs. 2D ROESY NMR experiments were also performed to prove the encapsulation and illustrate the stable 3D conformation of the inclusion complexes. The structural investigation was accomplished with molecular modeling studies. Finally, the radical scavenging activity of carvacrol and thymol was evaluated by the ABTS radical scavenging assay. An improvement of this activity was observed upon encapsulation. Taken together, these results evidence that the encapsulation in CDs could be valuable for applications of carvacrol and thymol in food. PMID:26877806

  17. Microenvironmental effects in the excited state properties of p-dimethylaminobenzonitrile complexed to alpha- and beta-cyclodextrin.

    PubMed

    Monti, Sandra; Bortolus, Pietro; Manoli, Francesco; Marconi, Giancarlo; Grabner, Gottfried; Köhler, Gottfried; Mayer, Bernd; Boszczyk, Wojciech; Rotkiewicz, Krystyna

    2003-03-01

    The steady state and time resolved fluorescence and the triplet-triplet absorption of p-dimethylaminobenzonitrile (DMABN) in presence of alpha- and beta-cyclodextrin (CD) were investigated at various host and guest concentrations and temperatures. The formation of 1:1 and 1:2 DMABN:alpha-CD and 1:1 and 2:2 complexes DMABN:beta-CD complexes was ascertained by applying global analysis methods. The "pure" fluorescence spectra as well as the emission quantum yields and lifetimes and the triplet properties of the various associates were determined. The role of environmental features in the radiative and non-radiative deactivation of the LE and ICT excited states of the complexed DMABN was elucidated. PMID:12713218

  18. Orthogonal separation on one beta-cyclodextrin column by switching reversed-phase liquid chromatography and hydrophilic interaction chromatography.

    PubMed

    Feng, Jia-tao; Guo, Zhi-mou; Shi, Hui; Gu, Jiang-ping; Jin, Yu; Liang, Xin-miao

    2010-06-15

    A dual retention combined with reversed-phase liquid chromatography (RP-LC) and hydrophilic interaction chromatography (HILIC) has been observed on beta-cyclodextrin (beta-CD) bonded stationary phase. A typical U-shaped retention curve was achieved owing to dual retention mechanism. Based on this observation, a beta-CD column can be operated under reversed-phase liquid chromatography (RP-LC) and hydrophilic interaction chromatography (HILIC) modes. Two-dimensional liquid chromatography (2D-LC) analysis can be realized on just a beta-CD column by switching these two different separation modes. In this study, off-line 2D-LC analysis for a natural product was carried out to prove the orthogonal separation between RP-LC and HILIC modes on a Click beta-CD column. Herba Hedyotis Diffusae, the whole grass of Hedyotis Diffusae wild was extracted with water, pretreated with macroporous resin and then first separated at RP-LC mode on the Click beta-CD column to obtain successive fractions, which were then reanalyzed at HILIC mode on the same Click beta-CD column. The result proved that both separation modes on the Click beta-CD column have good retention and peak shape, and these two separation modes have good orthogonality. 2D-LC analysis revealed abundant information in the natural product. Especially numerous minor components were enriched and separated. The mobile phase used in RP-LC and HILIC modes can be same and the switch between these two separation modes is easily realized by changing the ratio of the acetonitrile and water. Hence the mobile phase in this 2D-LC system is completely compatible. This advantage makes this combination is an appropriate 2D-LC method for the solutes having retention at both separation modes. PMID:20441989

  19. In-vitro evaluation of biphenylyl acetic acid-beta-cyclodextrin conjugates as colon-targeting prodrugs: drug release behaviour in rat biological media.

    PubMed

    Hirayama, F; Minami, K; Uekama, K

    1996-01-01

    Biphenylyl acetic acid was selectively conjugated to one of the primary hydroxyl groups of beta-cyclodextrin through an ester- or amide-linkage, and the physicochemical properties (aqueous solubility and hydrolysis) were investigated. Aqueous solubility of the conjugates was lower than those of either drug or parent beta-cyclodextrin. The amide conjugate was stable in aqueous solution and in rat biological fluids and gastrointestinal contents. The ester conjugate was hydrolysed to beta-cyclodextrin and biphenylyl acetic acid at moderate rates resulting in a V-shaped rate-pH profile in aqueous solution. The ester conjugate released the drug preferentially when incubated with the contents of caecum or colon, whereas no appreciable drug release was observed on incubation with contents of stomach or intestine, nor on incubation with intestinal or liver homogenates, nor on incubation with rat blood. The present results suggest that the ester-type drug conjugate of beta-cyclodextrin may serve as a colon-targeting prodrug. PMID:8722490

  20. Efficacy of attractive toxic sugar baits (ATSB) against Aedes albopictus with garlic oil encapsulated in beta-Cyclodextrin as the active ingredient

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We tested the efficacy of attractive toxic sugar bait (ATSB) with garlic oil microencapsulated in beta-cyclodextrin as active ingredient against Aedes albopictus in suburban Haifa, Israel. Two three-acre gardens with high numbers of Ae. albopictus were chosen for perimeter spray treatment with ATSB ...

  1. A conformational model of per-O-acetyl-cyclomaltoheptaose (-beta-cyclodextrin) in solution: detection of partial inversion of glucopyranose units by NMR spectroscopy.

    PubMed

    Uccello-Barretta, Gloria; Sicoli, Giuseppe; Balzano, Federica; Salvadori, Piero

    2003-05-01

    The stereochemical features of per-O-acetyl-cyclomaltoheptaose (-beta-cyclodextrin) have been investigated in solution by NMR spectroscopy, and the deviation of functionalised glucopyranose rings from 4C(1) chairs to skew-type conformations has been detected. PMID:12706976

  2. Genistein in 1:1 Inclusion Complexes with Ramified Cyclodextrins: Theoretical, Physicochemical and Biological Evaluation

    PubMed Central

    Danciu, Corina; Soica, Codruta; Oltean, Mircea; Avram, Stefana; Borcan, Florin; Csanyi, Erzsebet; Ambrus, Rita; Zupko, Istvan; Muntean, Delia; Dehelean, Cristina A.; Craina, Marius; Popovici, Ramona A.

    2014-01-01

    Genistein is one of the most studied phytocompound in the class of isoflavones, presenting a notable estrogenic activity and in vitro and/or in vivo benefits in different types of cancer such as those of the bladder, kidney, lung, pancreatic, skin and endometrial cancer. A big inconvenience for drug development is low water solubility, which can be solved by using hydrophilic cyclodextrins. The aim of this study is to theoretically analyze, based on the interaction energy, the possibility of a complex formation between genistein (Gen) and three different ramified cyclodextrins (CD), using a 1:1 molar ratio Gen:CD. Theoretical data were correlated with a screening of both in vitro and in vivo activity. Proliferation of different human cancer cell lines, antimicrobial activity and angiogenesis behavior was analyzed in order to see if complexation has a beneficial effect for any of the above mentioned activities and if so, which of the three CDs is the most suitable for the incorporation of genistein, and which may lead to future improved pharmaceutical formulations. Results showed antiproliferative activity with different IC50 values for all tested cell lines, remarkable antimicrobial activity on Bacillus subtilis and antiangiogenic activity as revealed by CAM assay. Differences regarding the intensity of the activity for pure and the three Gen complexes were noticed as explained in the text. The data represent a proof that the three CDs can be used for furtherer research towards practical use in the pharmaceutical and medical field. PMID:24473144

  3. Inclusion complex of a new propiconazole derivative with β-cyclodextrin: NMR, ESI–MS and preliminary pharmacological studies

    PubMed Central

    Marangoci, Narcisa; Mares, Mihai; Silion, Mihaela; Fifere, Adrian; Varganici, Cristian; Nicolescu, Alina; Deleanu, Calin; Coroaba, Adina; Pinteala, Mariana; Simionescu, Bogdan C.

    2011-01-01

    A novel inclusion complex of the propiconazole nitrate (NO3PCZ) with β-cyclodextrin (β-CD) was prepared by treatment of propiconazole (PCZ) with an acidic nitrating agent. The formation of NO3PCZ and its inclusion complex with β-CD has been studied by NMR, ESI–MS, TGA, DSC methods. Using the undecoupled signal in the HMBC correlation spectra, almost identical coupling constants of CH from trizolic ring of PCZ and NO3PCZ compounds (1J(HC)3=207 Hz, 1J(CH)5=214 Hz, for PCZ; 1J(HC)3=208 Hz and 1J(CH)5=215 Hz, for NO3PCZ) were determined, confirming that the geometry of the heterocyclic skeleton is identical in both the forms. The 1:1 stoichiometry of the complex was determined by ESI–MS and was confirmed using Scott's equation in DMSO and Higuchi and Connors equation in water. The solubility curve obtained for NO3PCZ in presence of β-CD in distilled water was constructed, resulting in a solubility diagram of AL type. Solubility of NO3PCZ in water was determined by DLS studies. The results showed that NO3PCZ was encapsulated within the β-CD cavity with a binding constant of 330 M-1 in DMSO and 975 M-1 in water. Preliminary pharmacological studies showed higher antifungal activities for NO3PCZ and its inclusion complex, compared with its PCZ analog. The acute toxicity of the complex is smaller than the pure or modified drug, recommending the inclusion complex as future promising therapeutic agents. PMID:25755979

  4. Investigation of the inclusion behavior of HP-β-cyclodextrin with polydatin in solution and its analytical application

    NASA Astrophysics Data System (ADS)

    An, Songsong; He, Jiang; Sun, Lijuan; Ren, Dong; Ban, Yihe

    2013-04-01

    The inclusion complex of the slight water solubility, polydatin (PD), with hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated for the first time in solution. The effect of HP-β-CD on the spectral feature of PD was measured using fluorescence technique by varying the concentrations of HP-β-CD. Meanwhile, the molecular mechanism of the formation of inclusion complex of PD with HP-β-CD was studied and discussed by molecular modeling. The experimental result clearly indicated that the benzene ring of PD was encapsulated within the HP-β-CD cavity to form a 1:1 stoichiometry host-guest compound. The apparent formation constants (K) was obtained by the typical double reciprocal plots and phase solubility studies. Due to the remarkable enhancement of the fluorescence intensity of PD, a spectrofluorimetric method was developed for the determination of PD in bulk aqueous solution in the presence of HP-β-CD. The linear range was 2.00 × 10-7-2.00 × 10-5 mol/L (r = 0.998) with the detection limit 9.50 × 10-9 mol/L. The present study provided useful information for a more rational determination of PD in serum with recoveries of 97-104%.

  5. Efficient synthesis of pure monotosylated beta-cyclodextrin and its dimers.

    PubMed

    Tripodo, Giuseppe; Wischke, Christian; Neffe, Axel T; Lendlein, Andreas

    2013-11-15

    6-O-Monotosyl-β-cyclodextrin (mono-Ts-βCD) is one of the most important intermediates in the production of substituted βCD. So far, performing the monotosylation reaction and, in particular, the purification steps was challenging, relied on toxic solvents, and resulted in long and expensive procedures at, importantly, low yields. Here, the reaction of cyclodextrin with p-toluenesulfonyl chloride in aqueous environment is described to obtain a highly pure mono-Ts-βCD, for which a single-step purification with a cation exchange resin was applied. With this synthetic route and purification, yields could be increased from typically <10-15% to 35%, and organic solvents could be avoided. As characterized by FTIR, mass spectrometry, elemental analysis, and NMR, mono-Ts-βCD was obtained with a molar purity of >98mol%. From mono-Ts-βCD, β-cyclodextrin dimers linked by ethylenediamine (bis-Et-βCD) were successfully prepared (yield 93%, purity 96mol%) in a one-step approach using an anion exchange resin to trap leaving groups that typically interfere in the reaction. This synthesis procedure with a direct collection of side-products may be a general strategy applicable for nucleophilic substitution of tosylated cyclodextrins. PMID:24060538

  6. Sorption of Ochratoxin A from aqueous solutions using beta-cyclodextrin-polyurethane polymer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The ability of a cyclodextrin-polyurethane polymer to remove ochratoxin A from aqueous solutions, including wine, was examined by batch rebinding assays and equilibrium sorption isotherms. The results were fit to two parameter models. Freundlich analysis of the sorption isotherm indicates the polyme...

  7. Increasing the solubility characteristics of albendazole with dimethyl-beta-cyclodextrin.

    PubMed

    Kata, M; Schauer, M

    1991-01-01

    Albendazole is a veterinary anthelminthic drug with excellent effect. Since it is only slightly soluble in water, it is processed in a suspension dosage form as a drench. The solubility and bioavailability of the pharmacon were successfully increased with cyclodextrin derivatives. PMID:1872189

  8. Study of β-cyclodextrin inclusion complexes with volatile molecules geraniol and α-terpineol enantiomers in solid state and in solution

    NASA Astrophysics Data System (ADS)

    Ceborska, Magdalena; Szwed, Kamila; Asztemborska, Monika; Wszelaka-Rylik, Małgorzata; Kicińska, Ewa; Suwińska, Kinga

    2015-11-01

    Geraniol and α-terpineol are insoluble in water volatile compounds. α-Terpineol is a potentially important agent for medical applications. Formation of molecular complexes with β-cyclodextrin would lead to the increase of water solubility and bioavailability. β-Cyclodextrin forms 2:2 inclusion complexes with both enantiomers of α-terpineol and their precursor geraniol. Solid state complexes are thoroughly characterized by single X-ray crystallography and their stability over vast range of temperatures is proven by TG analysis. Intermolecular host-guest, host-host and guest-guest interactions give good insight into the nature of formed inclusion complexes. Stability constants of the complexes in solution are determined by HPLC.

  9. NMR, surface tension and conductance study to investigate host-guest inclusion complexes of three sequential ionic liquids with β-cyclodextrin in aqueous media

    NASA Astrophysics Data System (ADS)

    Barman, Siti; Ekka, Deepak; Saha, Subhadeep; Roy, Mahendra Nath

    2016-08-01

    Host-guest inclusion complexes of three sequential cationic room temperature surface active ionic liquids, benzyltrialkylammonium chloride [(C6H5CH2)N(CnH2n+1)3Cl; where n = 1, 2, 4] with β-cyclodextrin in aqueous media have been studied using surface tension, conductance and NMR spectroscopy. All the studies have suggested that the hydrophobic benzyl group of ionic liquids is encapsulated inside into the cavity of β-cyclodextrin and played a crucial role in supporting the formation of inclusion complexes. The variation of the thermodynamic parameters with guest size, shape is used to draw inferences about contributions to the overall binding by means of the driving forces, viz., hydrophobic effect, steric hindrance, van der Waal force, and electrostatic force.

  10. Photochemistry and radiation chemistry of the β-cyclodextrin-ZnTSPP inclusion complex

    NASA Astrophysics Data System (ADS)

    Mosseri, S.; Mialocq, J. C.

    Steady-state radiolysis, pulse radiolysis combined with both optical and conductimetric analysis and steady-state photolysis have been used to characterize the intermediates and the stable products formed upon oxidation of ZnTSPP in aqueous solution in the presence and in the absence of β-cyclodextrin (β-CD). In the absence of β-CD, its oxidation either by the OH . primary species of the radiolysis of water of photooxidation by O 2 lead to mixtures of products (partially unidentified) which reflect the poor selectivity of the oxidizing species. In the presence of β-CD, a highly selective formation (99%) of the porphyrin dication is observed upon 422 nm photolysis of an aerated solution of ZnTSPP at pH = 12. The dramatic effect of the porphyrin complexation by β-CD is emphasized.

  11. Determination of heroin metabolites in human urine using capillary zone electrophoresis with beta-cyclodextrin and UV detection.

    PubMed

    Alnajjar, Ahmed; McCord, Bruce

    2003-10-15

    A method has been developed for the detection of a mixture of morphine, codeine, 6-acetyl morphine (6-AM) and normorphine using capillary zone electrophoresis (CZE). The method utilized urinary 6-AM as a diagnostic indicator of heroin abuse because it is not a product of either morphine or codeine metabolism. The electrophoretic separation was achieved using an uncoated (50 microm I.D.) fused-silica capillary, 77 cm long, containing the detector window 10.0 cm from the outlet end. The running buffer (pH 6.0) contained 50 mM sodium phosphate and 0.015 M beta-cyclodextrins (beta-CD). The samples were first extracted using a mixed-mode solid-phase extraction procedure and then analyzed by CZE. The UV absorbance detection was monitored at 214 nm. It has been found that beta-CDs can improve separation efficiency due to their hydrophobic cavity. The effect of the concentration of beta-CD and pH was also evaluated. The application of electrokinetic injection with field amplified sample stacking results in low detection limits (40 ng/ml for each analyte) and the method has good reproducibility, precision, accuracy, and high recovery. PMID:14550865

  12. Removal of organic compounds from water via cloud-point extraction with permethyl hydroxypropyl-[beta]-cyclodextrin

    SciTech Connect

    Warner-Schmid, D.; Hoshi, Suwaru; Armstrong, D.W. )

    1993-03-01

    Aqueous solutions of nonionic surfactants are known to undergo phase separations at elevated temperatures. This phenomenon is known as clouding,' and the temperature at which it occurs is refereed to as the cloud point. Permethylhydroxypropyl-[beta]-cyclodextrin (PMHP-[beta]-CD) was synthesized and aqueous solutions containing it were found to undergo similar cloud-point behavior. Factors that affect the phase separation of PMHP-[beta]-CD were investigated. Subsequently, the cloud-point extractions of several aromatic compounds (i.e., acetanilide, aniline, 2,2[prime]-dihydroxybiphenyl, N-methylaniline, 2-naphthol, o-nitroaniline, m-nitroaniline, p-nitroaniline, nitrobenzene, o-nitrophenol, m-nitrophenol, p-nitrophenol, 4-phenazophenol, 3-phenylphenol, and 2-phenylbenzimidazole) from dilute aqueous solution were evaluated. Although the extraction efficiency of the compounds varied, most can be quantitatively extracted if sufficient PMHP-[beta]-CD is used. For those few compounds that are not extracted (e.g., o-nitroacetanilide), the cloud-point procedure may be an effective one-step isolation or purification method. 18 refs., 2 figs., 3 tabs.

  13. Bucky (basket)ball. Stabilization of electrogenerated C[sub 60]- radical monoanion in water by means of cyclodextrin inclusion chemistry

    SciTech Connect

    Boulas, P.; Kutner, W.; Jones, M.T.; Kadish, K.M. )

    1994-01-27

    A water-soluble magenta [gamma]-cyclodextrin inclusion complex of C[sub 60] ([gamma]-CD/C[sub 60]) was prepared by a mild method which involved solubilizing C[sub 60] in carbon disulfide followed by extracting C[sub 60] with a [gamma]-CD aqueous ethanolic solution. The UV-visible spectroscopy of [gamma]-CD/C[sub 60] and spectroelectrochemistry of the electrogenerated [gamma]-CD/C[sub 60][sup [minus

  14. Effect of dimethyl-beta-cyclodextrin concentrations on the pulmonary delivery of recombinant human growth hormone dry powder in rats.

    PubMed

    Jalalipour, Monireh; Najafabadi, Abdolhossien Rouholamini; Gilani, Kambiz; Esmaily, Hadi; Tajerzadeh, Hosnieh

    2008-12-01

    The aim of this article is to prepare and characterize inhalable dry powders of recombinant human growth hormone (rhGH), and assess their efficacy for systemic delivery of the protein in rats. The powders were prepared by spray drying using dimethyl-beta-cyclodextrin (DMbetaCD) at different molar ratios in the initial feeds. Size exclusive chromatography was performed in order to determine protecting effect of DMbetaCD on the rhGH aggregation during spray drying. By increasing the concentration of DMbetaCD, rhGH aggregation was decreased from 9.67 (in the absence of DMbetaCD) to 0.84% (using DMbetaCD at 1000 molar ratio in the spray solution). The aerosol performance of the spray dried (SD) powders was evaluated using Andersen cascade impactor. Fine particle fraction values of 53.49%, 33.40%, and 23.23% were obtained using DMbetaCD at 10, 100, and 1000 molar ratio, respectively. In vivo studies showed the absolute bioavailability of 25.38%, 76.52%, and 63.97% after intratracheal insufflation of the powders produced after spray drying of the solutions containing DMbetaCD at 10, 100, and 1000 molar ratio, respectively in rat. In conclusion, appropriate cyclodextrin concentration was achieved considering the protein aggregation and aerosol performance of the SD powders and the systemic absorption following administration through the rat lung. PMID:18384154

  15. Poly-dopamine-beta-cyclodextrin: A novel nanobiopolymer towards sensing of some amino acids at physiological pH.

    PubMed

    Hasanzadeh, Mohammad; Sadeghi, Sattar; Bageri, Leyla; Mokhtarzadeh, Ahad; Karimzadeh, Ayub; Shadjou, Nasrin; Mahboob, Soltanali

    2016-12-01

    A novel nanobiopolymer film was electrodeposited on the surface of glassy carbon through cyclic voltammetry from dopamine, β-cyclodextrin, and phosphate buffer solution in physiological pH (7.40). The electrochemical behavior of polydopamine-Beta-cyclodextrin modified glassy carbon electrode was investigated for electro-oxidation and determination of some amino acids (l-Cysteine, l-Tyrosine, l-Glycine, and l-Phenylalanine). The modified electrode was applied for selected amino acid detection at physiological pH using cyclic voltammetry, differential pulse voltammetry and chronoamperometry, chronocoulometery. The linear concentration range of the proposed sensor for the l-Glycine, l-Cysteine, l-Tyrosine, and l-Phenylalanine were 0.2-70, 0.06-0.2, 0.01-0.1, and 0.2-10μM, while low limit of quantifications were 0.2, 0.06, 0.01, and 0.2μM, respectively. The modified electrode shows many advantages as an amino acid sensor such as simple preparation method without using any specific electron transfer mediator or specific reagent, good sensitivity, short response time, and long term stability. PMID:27612722

  16. Retention properties of hydrophobically end-capped poly(ethylene glycol)s on a beta-cyclodextrin support.

    PubMed

    Karakasyan, Carole; Millot, Marie-Claude; Jaulmes, Alain; Vidal-Madjar, Claire

    2006-09-15

    High-performance liquid chromatography (HPLC) was used to examine the retention behavior of monomethoxypoly(ethylene glycol)s bearing one hydrophobic naphthyl end group (Nap-MPEG) on beta-cyclodextrin polymer (poly-beta-CD) immobilized on a silica support, under isocratic elution conditions and using water as mobile phase. Studies of retentions and theoretical plate heights H were conducted at infinite dilution by comparing the behavior of Nap-MPEGs having different molecular weight (750, 1000 and 5000 g/mol). The larger is its molecular size, the lower is the retention of the polymer. The linear increase of H with mobile phase velocity reveals slow mass-transfer kinetics arising from the restricted diffusion into the pores of the support. The complexation constants between the Nap-MPEGs and beta-CD in solution (around 500M(-1)) were determined from the decrease of retention observed by adding increasing concentrations of hydroxypropyl beta-CD into the eluent. The peak profiles in mass-overload conditions were studied by fitting a model based upon bi-Langmuir kinetics which assumes a non-uniform support having two types of binding sites and apparent adsorption rate constants are used to describe mass-transfer kinetics. A three-parameter adsorption equilibrium isotherm was sufficient to account for the modifications of peak shapes observed when increasing amounts of polymer were injected. This result indicates an interaction with a heterogeneous poly-beta-CD support mainly composed of low affinity groups, non-saturable in the range of polymer concentration studied. An upper limit was estimated for the equilibrium constant (<1000 M(-1)) characterizing the affinity of Nap-MPEG for the non-saturable sites of the poly-beta-CD support. Large affinity constants (8-9 x 10(4)M(-1)) were found for the interaction of Nap-MPEGs with a small percentage of active sites. PMID:16828487

  17. Optimization of Microencapsulation of Fish Oil with Gum Arabic/Casein/Beta-Cyclodextrin Mixtures by Spray Drying.

    PubMed

    Li, Junjie; Xiong, Shanbai; Wang, Fang; Regenstein, Joe M; Liu, Ru

    2015-07-01

    Fish oil was encapsulated with gum arabic/casein/beta-cyclodextrin mixtures using spray drying. The processing parameters (solids concentration of the barrier solutions, ratio of oil to barrier materials, emulsifying temperature, and air inlet temperature) were optimized based on emulsion viscosity, emulsion stability, encapsulation efficiency, and yield. A suitable viscosity and high emulsion stability could increase encapsulation efficiency and yield. Encapsulation efficiency and yield were significantly affected by all the 4 parameters. Based on the results of orthogonal experiments, encapsulation efficiency and yield reached a maximum of 79.6% and 55.6%, respectively, at the optimal condition: solids concentration of 35%, ratios of oil to barrier materials of 3:7, emulsifying temperature of 55 °C, and air inlet temperature of 220 °C. Scanning electron microscopy analysis showed that fish oil microcapsules were nearly spherical with a smooth surface with droplet size ranging from 1 to 10 μm. PMID:26087831

  18. A luminescent beta-cyclodextrin-based Ru(phen)3 complex as DNA compactor, enzyme inhibitor, and translocation tracer.

    PubMed

    Liu, Yu; Chen, Yong; Duan, Zhong-Yu; Feng, Xi-Zeng; Hou, Sen; Wang, Chen; Wang, Rui

    2007-11-01

    A beta-cyclodextrin-based Ru(phen)(3) complex (1) has been synthesized and exhibits good luminescent behavior. Atomic force microscopic and scanning electron microscopic studies show that 1 can induce the aggregation of originally circular DNA to toroidal or spherical shapes. The morphology of these DNA aggregates changes following a pathway of naked circular DNA --> toroid with gaps --> solid toroid --> spherical aggregate, depending on the different 1/DNA (w/w) ratios, and their average diameters vary from the nanometer to micrometer scale. Owing to its capability of inducing the aggregation of DNA, 1 can be used as an inhibitor for DNA topoisomerase and DNA cleavage enzymes. Further studies by means of fluorescence microscopy indicate that 1 can also efficiently trace the translocation of DNA into 293T cells (the human embryonic kidney cell line). These observations consequently establish 1 as not only a potential DNA carrier but also a fluorescent DNA probe. PMID:19206682

  19. Elaboration of antibiofilm surfaces functionalized with antifungal-cyclodextrin inclusion complexes.

    PubMed

    Gharbi, Aïcha; Humblot, Vincent; Turpin, Frédéric; Pradier, Claire-Marie; Imbert, Christine; Berjeaud, Jean-Marc

    2012-07-01

    To tackle the loss of activity of surfaces functionalized by coating and covalently bound molecules to materials, an intermediate system implying the noncovalent immobilization of active molecules in the inner cavity of grafted cyclodextrins (CDs) was investigated. The antifungal and antibiofilm activities of the most stable complexes of Anidulafungin (ANF; echinocandin) and thymol (THY; terpen) in various CDs were demonstrated to be almost the same as the free molecules. The selected CD was covalently bond to self-assembled monolayers on gold surfaces. The immobilized antifungal agents reduced the number of culturable Candida albicans ATCC 3153 attached to the surface by 64 ± 8% for ANF and 75 ± 15% for THY. The inhibitory activity was persistent for THY-loaded samples, whereas it was completely lost for ANF-loaded surfaces after one use. However, reloading of the echinocandin restored the activity. Using fluorescent dying and confocal microscopy, it was proposed that the ANF-loaded surfaces inhibited the adherence of the yeasts, whereas the activity of immobilized THY was found fungicidal. This kind of tailored approach for functionalizing surfaces that could allow a progressive release of ANF or THY gave promising results but still needs to be improved to display a full activity. PMID:22268719

  20. Preparation and characterization of soluble branched ionic β-cyclodextrins and their inclusion complexes with triclosan.

    PubMed

    Gómez-Galván, Flor; Pérez-Álvarez, Leyre; Matas, Janire; Álvarez-Bautista, Arturo; Poejo, Joana; Duarte, Catarina M; Ruiz-Rubio, Leire; Vila-Vilela, Jose Luis; León, Luis M

    2016-05-20

    This study aims to synthesize, characterize and investigate the water solubility and cytotoxicity of branched anionic/cationic β-cyclodextrins (bβCDs) obtained by reaction with epichlorohydrin and chloroacetic acid or choline chloride, respectively, by a single step polycondensation reaction. Obtained ionic bβCDs were investigated as an attempt to comparatively study anionic and cationic bβCDs. Water solubility of both ionic derivatives was similar (400mg/mL) at neutral and basic pHs and remarkably higher than that of their neutral homologues. Additionally, a pH-dependent solubility of anionic bβCDs was observed. Cytotoxicity of ionic bβCDs was evaluated on Human colon carcinoma Caco-2 cells and high cell viability (>99%) was observed in the range of 0-100mg/mL for anionic and cationic samples, in the same range of that of neutral and parent β-CDs. Additionally, complexes formation capacity with triclosan, a poor water soluble antimicrobial agent, was confirmed by several techniques observing a complexation limit around 4mg/mL for both systems and higher stability constant for anionic bβCDs than cationic derivatives. PMID:26917385

  1. pH and temperature stability of (-)-epigallocatechin-3-gallate-β-cyclodextrin inclusion complex-loaded chitosan nanoparticles.

    PubMed

    Liu, Fei; Majeed, Hamid; Antoniou, John; Li, Yue; Ma, Yun; Yokoyama, Wallace; Ma, Jianguo; Zhong, Fang

    2016-09-20

    The oxidative stability of (-)-epigallocatechin-3-gallate (EGCG) incorporated as inclusion complexes (ICs) in sulfobutylether-β-cyclodextrin sodium (SBE-β-CD) and then ionotropically crosslinked with chitosan hydrochloride (CSH) into nanoparticles were investigated. EGCG-loaded CSH-SBE-β-CD nanoparticles (CSNs) were physically unstable at higher pH and temperature. The particle size of CSNs was unchanged in the pH range of 3-5, but the microenvironment of EGCG-IC appeared to be intact until the pH increased to 6.5 by fluorescence spectroscopy. The physical structure of EGCG-ICs was also affected during storage in addition to CSNs, which was further affected as temperature increased from 25 to 55°C. The decrease in antioxidant activities of EGCG-ICs and free EGCG with increasing pH, storage time and temperature were modest compared to the prominent decreases in antioxidant activities of EGCG-loaded CSNs. The extreme entrapment of EGCG-ICs and/or free EGCG in the aggregated CSNs restricted the release of EGCG, thus inhibiting the antioxidant activities. PMID:27261758

  2. Fabrication of electrospun polylactic acid nanofilm incorporating cinnamon essential oil/β-cyclodextrin inclusion complex for antimicrobial packaging.

    PubMed

    Wen, Peng; Zhu, Ding-He; Feng, Kun; Liu, Fang-Jun; Lou, Wen-Yong; Li, Ning; Zong, Min-Hua; Wu, Hong

    2016-04-01

    A novel antimicrobial packaging material was obtained by incorporating cinnamon essential oil/β-cyclodextrin inclusion complex (CEO/β-CD-IC) into polylacticacid (PLA) nanofibers via electrospinning technique. The CEO/β-CD-IC was prepared by the co-precipitation method and SEM and FT-IR spectroscopy analysis indicated the successful formation of CEO/β-CD-IC, which improved the thermal stability of CEO. The CEO/β-CD-IC was then incorporated into PLA nanofibers by electrospinning and the resulting PLA/CEO/β-CD nanofilm showed better antimicrobial activity compared to PLA/CEO nanofilm. The minimum inhibitory concentration (MIC) of PLA/CEO/β-CD nanofilm against Escherichia coli and Staphylococcus aureus was approximately 1 mg/ml (corresponding CEO concentration 11.35 μg/ml) and minimum bactericidal concentration (MBC) was approximately 7 mg/ml (corresponding CEO concentration 79.45 μg/ml). Furthermore, compared with the casting method, the mild electrospinning process was more favorable for maintaining greater CEO in the obtained film. The PLA/CEO/β-CD nanofilm can effectively prolong the shelf life of pork, suggesting it has potential application in active food packaging. PMID:26593582

  3. Effect of preparation processes and structural insight into the supermolecular system: Bisacodyl and β-cyclodextrin inclusion complex.

    PubMed

    Li, Shanshan; Zhai, Yuanming; Yan, Jin; Wang, Lili; Xu, Kailin; Li, Hui

    2016-01-01

    In this study, β-cyclodextrin (β-CD) and bisacodyl were chosen as model host and guest molecule to explore the effect of preparation processes on the physicochemical properties of inclusion complexes (ICs) and to gain an insight into the structure of ICs. The influence of temperature and pH on complexation was studied by multiple temperature-pH phase solubility analysis. The most favorable conformation was predicted by molecular modeling using AutoDock. (1)H nuclear magnetic resonance and rotating frame nuclear Overhauser effect spectroscopy further confirmed the structure. Moreover, bisacodyl · β-CD ICs in solid state were successfully prepared via three different procedures (co-crystallization, co-evaporation, and co-grinding) and fully characterized by several solid-state techniques, namely, Fourier transform infrared spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, solid-state NMR spectroscopy, and scanning electron microscopy. It was found that acid solution and low temperature were unfavorable for formation of bisacodyl · β-CD. The pyridine moiety was suggested to be enclosed in the hydrophobic cavity of β-CD. The complexes prepared using co-crystallization showed properties similar to those prepared using co-evaporation. Moreover, ICs obtained by co-evaporation and co-grinding had higher loading efficiency, water solubility, and dissolution rate than ICs obtained by co-crystallization. PMID:26478306

  4. Release studies of trans-anethole from β-cyclodextrin solid inclusion complexes by Multiple Headspace Extraction.

    PubMed

    Kfoury, Miriana; Auezova, Lizette; Greige-Gerges, Hélène; Larsen, Kim L; Fourmentin, Sophie

    2016-10-20

    This study aimed to evaluate the effect of the preparation method, temperature and humidity on the release of aroma from β-cyclodextrin (β-CD) solid inclusion complexes (IC). Therefore β-CD/trans-anethole (β-CD/AN) IC were prepared by freeze-drying (FD) and co-precipitation coupled to FD (Cop-FD). Release experiments were performed at various temperatures and relative humidities (RH). Multiple headspace extraction-gas chromatography (MHE) was used to determine the loading capacity (LC) and encapsulation efficiency (EE%) and perform release studies. Results underlined that the quantification of encapsulated AN by MHE requires the IC dissolution. The release of AN was accelerated by increases in RH and temperature. However, it was quite negligible below 75% RH. The release behavior of AN was well simulated by Avrami's equation. Cop-FD IC retained more efficiently AN and the release depended on the preparation method and treatment conditions. Thus, the preparation method could be chosen based on the application. PMID:27474677

  5. Biodiesel fuel production from waste cooking oil by the inclusion complex of heteropoly acid with bridged bis-cyclodextrin.

    PubMed

    Zou, Changjun; Zhao, Pinwen; Shi, Lihong; Huang, Shaobing; Luo, Pingya

    2013-10-01

    The inclusion complex of Cs2.5H0.5PW12O40 with bridged bis-cyclodextrin (CsPW/B) is prepared as a highly efficient catalyst for the direct production of biodiesel via the transesterification of waste cooking oil. CsPW/B is characterized by X-ray diffraction, and the biodiesel is analyzed by Gas Chromatography-Mass Spectrometer. The conversion rate of waste cooking oil is up to 94.2% under the optimum experimental conditions that are methanol/oil molar ratio of 9:1, catalyst dosage of 3 wt%, temperature of 65 °C and reaction time of 180 min. The physical properties of biodiesel sample satisfy the requirement of ASTM D6751 standards. The novel CsPW/B catalyst used for the transesterification can lead to 96.9% fatty acid methyl esters and 86.5% of the biodiesel product can serve as the ideal substitute for diesel fuel, indicating its excellent potential application in biodiesel production. PMID:23972395

  6. [Effect of β-cyclodextrin inclusion complex on transport of major components of Xiangfu Siwu decoction essential oil in Caco-2 cell monolayer model].

    PubMed

    Xi, Jun-zuan; Qian, Da-wei; Duan, Jin-ao; Liu, Pei; Zhu, Yue; Zhu, Zhen-hua; Zhang, Li

    2015-08-01

    Although the essential oil of Xiangfu Siwu decoction (XFSWD) has strong pharmacological activity, its special physical and chemical properties restrict the clinical application and curative effect. In this paper, Xiangfu Siwu decoction essential oil (XFS-WO) was prepared by forming inclusion complex with β-cyclodextrin (β-CD). The present study is to investigate the effect of β-CD inclusion complex on the transport of major components of XFSWO using Caco-2 cell monolayer model, thus to research the effect of this formation on the absorption of drugs with low solubility and high permeability, which belong to class 2 in biopharmaceutics classification system. A sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of senkyunolide A, 3-n-butylphthalide, Z-ligustilide, dehydrocostus lactone and α-cyperone, which are active compounds in XFSWO. The transport parameters were analyzed and compared in free oil and its β-CD inclusion complex. The result revealed that the formation of XFSWO/β-CD inclusion complex has significantly increased the transportation and absorption of major active ingredients than free oil. Accordingly, it can be speculated that cyclodextrin inclusion complex can improve bioavailability of poorly water-soluble drugs. Above all these mentioned researches, it provided foundation and basis for physiological disposition and pharmaceutical study of XFSWD. PMID:26677694

  7. Kinetics of inhibition of polyphenol oxidase mediated browning in apple juice by beta-cyclodextrin and L-ascorbate-2-triphosphate.

    PubMed

    Gacche, R N; Zore, G B; Ghole, V S

    2003-02-01

    Polyphenol Oxidase (PPO) mediated browning in raw fruits and vegetables is a major cause of quality deterioration in fruits and vegetables and derived food products. Here the rate of browning reaction in apple juice treated individually and in combination (1:1) of beta-Cyclodextrin (beta-CD) and L-Ascorbate-2-triphosphate (L-AATP) is described. It was observed that the rate of quinone formation can be minimized using a combination of beta-CD and L-AATP as compared to individual treatment with these agents. Kinetic experiments revealed that both compounds are non-competitive inhibitors of PPO. PMID:12751814

  8. Inclusion complexation of sulfapyridine with α- and β-cyclodextrins: Spectral and molecular modeling study

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Siva, S.; Saravanan, J.

    2013-12-01

    The inclusion complexes of sulfapyridine (SFP) with α-CD and β-CD were investigated by absorption, fluorescence, time-resolved fluorescence, FTIR, DSC, XRD, 1H NMR, SEM, TEM and molecular modeling methods. The normal fluorescence takes place from locally excited (LE) state while twisted intramolecular charge transfer (TICT) is responsible for highly Stokes shifted fluorescence. The enhancement of TICT emission in both CDs suggesting that the inclusion process plays the major role in this emission. The spectral shifts revealed that part of pyridine ring of SFP is entrapped in the CDs cavities. TEM images confirmed round shaped nanoparticles with the average size about 20-50 nm were observed in SFP with α-CD and β-CD inclusion complexes. PM3 calculations have suggested that the large stabilization of excited singlet state of SFP with twisted conformation occurring at the amide SN bond between the electron donor group (aniline ring) and the electron acceptor group (pyridine ring).

  9. Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

    PubMed Central

    Amiel, Catherine; Duroux, Laurent; Larsen, Kim Lambertsen; Städe, Lars Wagner; Wimmer, Reinhard; Wintgens, Véronique

    2015-01-01

    Summary Novel (S)-camptothecin–dextran polymers were obtained by “click” grafting of azide-modified (S)-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were prepared with a degree of substitution of (S)-camptothecin between 3.1 and 10.2%. The binding properties with β-cyclodextrin and β-cyclodextrin polymers were measured by isothermal titration calorimetry and fluorescence spectroscopy, showing no binding with β-cyclodextrin but high binding with β-cyclodextrin polymers. In aqueous solution nanoparticles were formed from association between the (S)-camptothecin–dextran polymers and the β-cyclodextrin polymers. PMID:25670998

  10. Spectroscopic and electrochemical studies on the interaction of an inclusion complex of β-cyclodextrin with 2,6-dinitrophenol in aqueous and solid phases

    NASA Astrophysics Data System (ADS)

    Srinivasan, K.; Stalin, T.; Shanmugapriya, A.; Sivakumar, K.

    2013-03-01

    The inclusion complex of 2,6-dinitrophenol (2,6-DNP) with β-cyclodextrin (β-CD) in solution phase was studied by UV-visible spectrophotometer and electrochemical (cyclic voltammetry) methods. The prototropic behaviors of 2,6-DNP were studied. The binding constant of 'β-CD:2,6-DNP' inclusion complex was calculated using Benesi-Hildebrand plot at 303 K. Thermodynamic parameter (ΔG) involved in the complex formation also calculated. It indicates that the reaction is spontaneous and exergonic process. Formation of solid inclusion complex between β-CD and 2,6-DNP was characterized by 1H NMR, FT-IR, XRD techniques and SEM morphological studies. The β-CD:2,6-DNP inclusion complex obtained by molecular docking studies is in good correlation with the results obtained through experimental methods.

  11. Processing polymers with cyclodextrins

    NASA Astrophysics Data System (ADS)

    Williamson, Brandon Robert

    Cyclodextrins (CDs) are cyclic starch molecules that have the unique ability to include a variety of small molecules and polymers inside their cavities, forming "Inclusion Complexes" (ICs). While much work has been done to understand the formation and behavior of these ICs, far less is known about the fundamental property changes that can occur when CD is used to alter polymer chain morphology. The goal of my graduate research has been to discover different ways to improve upon existing polymer properties through CD processing, as well as explore the possibility of creating a novel type of IC using non-traditional forms of cyclodextrin. Poly(ε-caprolactone) (PCL) was processed with alpha-CD to form an IC. The cyclodextrin was then stripped away to yield a PCL with elongated, unentangled, and constrained polymer chains, a process referred to as coalescence. The physical and rheological property changes resulting from this coalescence were then examined. It was found that reorganizing PCL in this manner resulted in an increase in the melt crystallization temperature of up to 25°C. Coalescence also decreased the tan delta of the material and increased the average hardness and Young's modulus by 33 and 53%, respectively. Non-stoichiometric ICs (NS-ICs), or ICs with at least parts of some polymer chains uncovered, were formed between poly (methyl methacrylate) (PMMA) and gamma-CD as well as a synthesized poly(ε-caprolactone)-poly(propylene glycol)-poly(ε-caprolactone) (PCL-PPG-PCL) triblock copolymer and beta-CD. The property changes of the non-complexed polymer chains were then studied. The PMMA/gamma-CD NS-IC samples were determined to be extremely heterogeneous, however glass transition temperature increases of up to 27°C above that of as-received PMMA were observed. Diffraction data for the PMMA NS-ICs suggests slight crystallinity at partial coverage, with a similar crystal structure to that of the fully covered IC. XRD, DSC and FTIR data revealed an almost

  12. Method for the separation of the unconjugates and conjugates of chenodeoxycholic acid and deoxycholic acid by two-dimensional reversed-phase thin layer chromatography with methyl beta-cyclodextrin.

    PubMed

    Momose, T; Mure, M; Iida, T; Goto, J; Nambara, T

    1998-06-19

    A simple and efficient method for the separation of individual unconjugated bile acids and their glycine- and taurine-amidated, 3-sulfated, 3-glucosylated and 3-glucuronidated conjugates is described. The method involves the use of a two-dimensional (2D) reversed-phase (RP) high-performance thin-layer chromatographic (HPTLC) technique with methyl beta-cyclodextrin (Me-beta-CD). Five major unconjugated bile acids, chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), ursodeoxycholic acid and lithocholic acid, and their conjugates were examined as the solutes. A high degree of separation of individual bile acids in each homologous series was achieved on a RP-HPTLC plate by developing with aqueous methanol in the first dimension and the same solvent system containing Me-beta-CD in the second dimension. In particular, all of the six 'difficult-to-separate' pairs, unconjugated CDCA and DCA and their conjugated forms with glycine, taurine, sulfuric acid, D-glucose and D-glucuronic acid, were effectively resolved by adding Me-beta-CD in the aqueous mobile phases with the formers having larger mobilities than the latter. The application of this 2D inclusion RP-HPLC method to the separation of glycine-conjugated bile acids in human bile is also described. The present method would be useful for separating and characterizing these bile acids present in biological materials. PMID:9691303

  13. Enzymatic synthesis of dimaltosyl-{beta}-cyclodextrin via a transglycosylation reaction using TreX, a Sulfolobus solfataricus P2 debranching enzyme

    SciTech Connect

    Kang, Hee-Kwon; Cha, Hyunju; Yang, Tae-Joo; Park, Jong-Tae; Lee, Seungjae; Kim, Young-Wan; Auh, Joong-Hyuck; Okada, Yasuyo; Kim, Jung-Wan; Cha, Jaeho; Kim, Chung Ho; Park, Kwan-Hwa

    2008-02-01

    Di-O-{alpha}-maltosyl-{beta}-cyclodextrin ((G2){sub 2}-{beta}-CD) was synthesized from 6-O-{alpha}-maltosyl-{beta}-cyclodextrin (G2-{beta}-CD) via a transglycosylation reaction catalyzed by TreX, a debranching enzyme from Sulfolobus solfataricus P2. TreX showed no activity toward glucosyl-{beta}-CD, but a transfer product (1) was detected when the enzyme was incubated with maltosyl-{beta}-CD, indicating specificity for a branched glucosyl chain bigger than DP2. Analysis of the structure of the transfer product (1) using MALDI-TOF/MS and isoamylase or glucoamylase treatment revealed it to be dimaltosyl-{beta}-CD, suggesting that TreX transferred the maltosyl residue of a G2-{beta}-CD to another molecule of G2-{beta}-CD by forming an {alpha}-1,6-glucosidic linkage. When [{sup 14}C]-maltose and maltosyl-{beta}-CD were reacted with the enzyme, the radiogram showed no labeled dimaltosyl-{beta}-CD; no condensation product between the two substrates was detected, indicating that the synthesis of dimaltosyl-{beta}-CD occurred exclusively via transglycosylation of an {alpha}-1,6-glucosidic linkage. Based on the HPLC elution profile, the transfer product (1) was identified to be isomers of 6{sup 1},6{sup 3}- and 6{sup 1},6{sup 4}-dimaltosyl-{beta}-CD. Inhibition studies with {beta}-CD on the transglycosylation activity revealed that {beta}-CD was a mixed-type inhibitor, with a K{sub i} value of 55.6 {mu}mol/mL. Thus, dimaltosyl-{beta}-CD can be more efficiently synthesized by a transglycosylation reaction with TreX in the absence of {beta}-CD. Our findings suggest that the high yield of (G2){sub 2}-{beta}-CD from G2-{beta}-CD was based on both the transglycosylation action mode and elimination of the inhibitory effect of {beta}-CD.

  14. Polymer-free nanofibers from vanillin/cyclodextrin inclusion complexes: high thermal stability, enhanced solubility and antioxidant property.

    PubMed

    Celebioglu, Asli; Kayaci-Senirmak, Fatma; İpek, Semran; Durgun, Engin; Uyar, Tamer

    2016-07-13

    Vanillin/cyclodextrin inclusion complex nanofibers (vanillin/CD-IC NFs) were successfully obtained from three modified CD types (HPβCD, HPγCD and MβCD) in three different solvent systems (water, DMF and DMAc) via an electrospinning technique without using a carrier polymeric matrix. Vanillin/CD-IC NFs with uniform and bead-free fiber morphology were successfully produced and their free-standing nanofibrous webs were obtained. The polymer-free CD/vanillin-IC-NFs allow us to accomplish a much higher vanillin loading (∼12%, w/w) when compared to electrospun polymeric nanofibers containing CD/vanillin-IC (∼5%, w/w). Vanillin has a volatile nature yet, after electrospinning, a significant amount of vanillin was preserved due to complex formation depending on the CD types. Maximum preservation of vanillin was observed for vanillin/MβCD-IC NFs which is up to ∼85% w/w, besides, a considerable amount of vanillin (∼75% w/w) was also preserved for vanillin/HPβCD-IC NFs and vanillin/HPγCD-IC NFs. Phase solubility studies suggested a 1 : 1 molar complexation tendency between guest vanillin and host CD molecules. Molecular modelling studies and experimental findings revealed that vanillin : CD complexation was strongest for MβCD when compared to HPβCD and HPγCD in vanillin/CD-IC NFs. For vanillin/CD-IC NFs, water solubility and the antioxidant property of vanillin was improved significantly owing to inclusion complexation. In brief, polymer-free vanillin/CD-IC NFs are capable of incorporating a much higher loading of vanillin and effectively preserve volatile vanillin. Hence, encapsulation of volatile active agents such as flavor, fragrance and essential oils in electrospun polymer-free CD-IC NFs may have potential for food related applications by integrating the particularly large surface area of NFs with the non-toxic nature of CD and inclusion complexation benefits, such as high temperature stability, improved water solubility and an enhanced

  15. Supramolecular interaction of ethylenediamine linked beta-cyclodextrin dimer and berberine hydrochloride by spectrofluorimetry and its analytical application.

    PubMed

    Liu, Fang; Liang, Hui-Ling; Xu, Ke-Hua; Tong, Li-Li; Tang, Bo

    2007-11-15

    The supramolecular interaction of beta-cyclodextrin dimer with berberine hydrochloride was studied in aqueous KH2PO4-H3PO4 buffer solution of pH 2.00 at room temperature by spectrofluorimetry. The apparent association constant of the complex was 1.53 x 10(4) L mol(-1). Based on the significant enhancement of fluorescence intensity of supramolecular sandwich complexes, a spectrofluorimetric method with high sensitivity and selectivity was developed for the determination of berberine hydrochloride in aqueous solution in presence of ethylenediamine linked beta-CD dimer. The linear range of the method was 12.8-1.00 x 10(4 )ng mL(-1) with the detection limit 3.6 ng mL(-1). There was no interference from the normally used in tablets and serum constituents. The proposed method was successfully applied to the determination of berberine hydrochloride in tablets and serum. And then it has a promising potential in therapeutic drug monitoring, pharmacokinetics and clinical application. PMID:18371623

  16. 6A-O-[(4-biphenylyl)acetyl]-alpha-, -beta-, and -gamma-cyclodextrins and 6A-deoxy-6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and -gamma-cyclodextrins: potential prodrugs for colon-specific delivery.

    PubMed

    Uekama, K; Minami, K; Hirayama, F

    1997-08-15

    Cyclodextrins (CyDs) are known to be fermented to small saccharides by colonic microflora, whereas they are only slightly hydrolyzable and thus are not easily absorbed in the stomach and small intestine. This property of CyDs is particularly useful for colon-specific delivery of drugs. In this study, an antiinflammatory 4-biphenylylacetic acid (BPAA) was selectively conjugated onto one of the primary hydroxyl groups of alpha-, beta-, and gamma-CyDs through an ester or amide linkage, 6A-O-[(4-biphenylyl)acetyl[-alpha-, -beta-, and -gamma-CyDs (1-3) and 6A-deoxy-6A-[[(4-biphenylyl)acetyl]amino]-alpha-, -beta-, and -gamma-CyDs (4-6). In rat cecal and colonic contents (10%, w/v), 1 and 3 released more than 95% of BPAA within 1-2 h, and 2 released about 50% of the drug within 12 h. The amide prodrugs, 4-6, did not release BPAA in the cecal contents, but gave BPAA/maltose or BPAA/triose conjugates linked through an amide bond. On the other hand, these prodrugs were found to be stable in the contents of rat stomachs and small intestines, in intestinal or liver homogenates, and in rat blood. The serum levels of BPAA increased about 3 h after oral administration of 1 and 3 to rats, accompanying a marked increase in the serum levels, whereas 2 and 4-6 resulted in little increase of the serum levels. These facts suggest that BPAA is released after the ring opening of CyDs followed by the ester hydrolysis, and the BPAA activation takes place site-specifically in the cecum and colon. Therefore, the present CyD prodrug approach provides a versatile means of constructing a novel colon-specific drug delivery system. PMID:9276021

  17. Novel pharmaceutical composition of bradykinin potentiating penta peptide with beta-cyclodextrin: physical-chemical characterization and anti-hypertensive evaluation.

    PubMed

    Denadai, Angelo M L; Ianzer, Danielle; Alcântara, Antônio Flávio de C; Santoro, Marcelo M; Santos, Cynthia F F; Lula, Ivana Silva; de Camargo, Antônio C M; Faljoni-Alario, Adelaide; dos Santos, Robson A S; Sinisterra, Rubén D

    2007-05-01

    This work describes chemical properties and anti-hypertensive activity of an oral pharmaceutical formulation obtained from the complexation of beta-cyclodextrin (beta-CD) with bradykinin potentiating penta peptide (BPP-5a) founded in the Bothrops jararaca poison. Physical chemistry characterizations were recorded in order to investigate the intermolecular interactions between species in complex. Circular dichroism data indicated conformational changes of BPP-5a upon complexation with beta-CD. ROESY and theoretical calculations showed a selective approximation of triptophan moiety into cavity of beta-CD. Isothermal titration calorimetry data indicated an exothermic formation of the complex, which is accomplished by reduction of entropy. The anti-hypertensive activity of the BPP-5a/beta-CD complex has been evaluated in spontaneous hypertensive rats, showing better results than pure BPP-5a. PMID:17196774

  18. Inclusion complexes of triphenylphosphine derivatives and peracetylated-β-cyclodextrin in supercritical carbon dioxide

    NASA Astrophysics Data System (ADS)

    Galia, A.; Navarre, E. C.; Filardo, G.; Scialdone, O.; Monflier, E.

    2008-07-01

    The supramolecular chemistry of peracetylated-β-CD (perAc-β-CD) as a host for triphenyphosphine derivatives has been studied in supercritical (scCO2) using UV absorption spectroscopy. It was found that the association constant in scCO2 at 40°C and 300 bar is 10 to 1000 times smaller compared to analogous systems in aqueous solvent. Studies of the thermodynamics of the inclusion process found an enthalpy of association of -30 kJ/mole and an entropy of -55 J/moleK. This difference with respect to water is attributed to the absence of the hydrophobic effect in scCO2 due to the much smaller polarity of scCO2 versus water. To further explore the effect of the solvent on the association constant, values of solvent polarity intermediate between the limits of scCO2 and water could be useful. To this end, methanol is added to the scCO2 as a cosolvent to modify the overall polarity. By taking advantage of the tunability of the supercritical phase, a wide range of solvent polarity can be accessed by varying the temperature (35 to 50°C), pressure (200 to 400 bar), and mole fraction of methanol. This study is pursued to obtain a better comprehension of the inclusion process in CO2-based supercritical fluids to make the association constant of the phosphine-perAc-β-CD system comparable to those observed in aqueous systems.

  19. Gold nanoparticles interacting with β-cyclodextrin-phenylethylamine inclusion complex: a ternary system for photothermal drug release.

    PubMed

    Sierpe, Rodrigo; Lang, Erika; Jara, Paul; Guerrero, Ariel R; Chornik, Boris; Kogan, Marcelo J; Yutronic, Nicolás

    2015-07-22

    We report the synthesis of a 1:1 β-cyclodextrin-phenylethylamine (βCD-PhEA) inclusion complex (IC) and the adhesion of gold nanoparticles (AuNPs) onto microcrystals of this complex, which forms a ternary system. The formation of the IC was confirmed by powder X-ray diffraction and NMR analyses ((1)H and ROESY). The stability constant of the IC (760 M(-1)) was determined using the phase solubility method. The adhesion of AuNPs was obtained using the magnetron sputtering technique, and the presence of AuNPs was confirmed using UV-vis spectroscopy (surface plasmon resonance effect), which showed an absorbance at 533 nm. The powder X-ray diffractograms of βCD-PhEA were similar to those of the crystals decorated with AuNPs. A comparison of the one- and two-dimensional NMR spectra of the IC with and without AuNPs suggests partial displacement of the guest to the outside of the βCD due to attraction toward AuNPs, a characteristic tropism effect. The size, morphology, and distribution of the AuNPs were analyzed using TEM and SEM. The average size of the AuNPs was 14 nm. Changes in the IR and Raman spectra were attributed to the formation of the complex and to the specific interactions of this group with the AuNPs. Laser irradiation assays show that the ternary system βCD-PhEA-AuNPs in solution enables the release of the guest. PMID:26091143

  20. β-Cyclodextrin-Based Inclusion Complexation Bridged Biodegradable Self-Assembly Macromolecular Micelle for the Delivery of Paclitaxel.

    PubMed

    Chen, Yanzuo; Huang, Yukun; Qin, Dongdong; Liu, Wenchao; Song, Chao; Lou, Kaiyan; Wang, Wei; Gao, Feng

    2016-01-01

    In this study, a novel adamantanamine-paclitaxel (AD-PTX) incorporated oligochitosan- carboxymethyl-β-cyclodextrin (CSO-g-CM-β-CD) self-assembly macromolecular (CSO-g-CM-β-CD@AD-PTX) micelle was successfully prepared in water through sonication. The formed molecules were characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (NMR) spectroscopy, two-dimensional NMR, elemental analysis, and liquid chromatography-mass spectrometry, while the correspondent micelles were characterized by dynamic light scattering and transmission electron microscopy. We showed that the macromolecular micelle contained a spherical core-shell structure with a diameter of 197.1 ± 3.3 nm and zeta potential of -19.1 ± 4.3 mV. The CSO-g-CM-β-CD@AD-PTX micelle exhibited a high drug-loading efficacy up to 31.3%, as well as a critical micelle concentration of 3.4 × 10-7 M, which indicated good stability. Additionally, the in vitro release profile of the CSO-g-CM-β-CD@AD-PTX micelle demonstrated a long-term release pattern, 63.1% of AD-PTX was released from the micelle during a 30-day period. Moreover, the CSO-g-CM-β-CD@AD-PTX micelle displayed cytotoxicity at a sub-μM scale similar to PTX in U87 MG cells, and CSO-g-CM-β-CD exhibited a good safety profile by not manifesting significant toxicity at concentrations up to 100 μM. These results indicated that β-CD-based inclusion complexation resulting in biodegradable self-assembled macromolecular micelles can be utilized as nanocarrier, and may provide a promising platform for drug delivery in the future medical applications. PMID:26964047

  1. β-Cyclodextrin-Based Inclusion Complexation Bridged Biodegradable Self-Assembly Macromolecular Micelle for the Delivery of Paclitaxel

    PubMed Central

    Chen, Yanzuo; Huang, Yukun; Qin, Dongdong; Liu, Wenchao; Song, Chao; Lou, Kaiyan; Wang, Wei; Gao, Feng

    2016-01-01

    In this study, a novel adamantanamine-paclitaxel (AD-PTX) incorporated oligochitosan- carboxymethyl-β-cyclodextrin (CSO-g-CM-β-CD) self-assembly macromolecular (CSO-g-CM-β-CD@AD-PTX) micelle was successfully prepared in water through sonication. The formed molecules were characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance (NMR) spectroscopy, two-dimensional NMR, elemental analysis, and liquid chromatography-mass spectrometry, while the correspondent micelles were characterized by dynamic light scattering and transmission electron microscopy. We showed that the macromolecular micelle contained a spherical core-shell structure with a diameter of 197.1 ± 3.3 nm and zeta potential of −19.1 ± 4.3 mV. The CSO-g-CM-β-CD@AD-PTX micelle exhibited a high drug-loading efficacy up to 31.3%, as well as a critical micelle concentration of 3.4 × 10-7 M, which indicated good stability. Additionally, the in vitro release profile of the CSO-g-CM-β-CD@AD-PTX micelle demonstrated a long-term release pattern, 63.1% of AD-PTX was released from the micelle during a 30-day period. Moreover, the CSO-g-CM-β-CD@AD-PTX micelle displayed cytotoxicity at a sub-μM scale similar to PTX in U87 MG cells, and CSO-g-CM-β-CD exhibited a good safety profile by not manifesting significant toxicity at concentrations up to 100 μM. These results indicated that β-CD-based inclusion complexation resulting in biodegradable self-assembled macromolecular micelles can be utilized as nanocarrier, and may provide a promising platform for drug delivery in the future medical applications. PMID:26964047

  2. Thermodynamic study of β-cyclodextrin-dye inclusion complexes using gradient flow injection technique and molecular modeling.

    PubMed

    Izadmanesh, Y; Ghasemi, Jahan B

    2016-08-01

    Gradient flow injection technique-diode array spectrophotometry was applied for β-cyclodextrin (β-CD)-dye inclusion complex studies. A single injection of a small amount of mixed β-CD-dye solution (100μl) into the carrier solution of the dye and recording the spectra gave the titration data. The mole ratio data were calculated by calibrating the dispersion pattern using a calibrator dye (rose bengal). Model-based multivariate methods were used to analyze the spectral-mole ratio data and, as a result, estimate stability constants and concentration-spectral profiles. Reliability was tested by applying this method to study the β-CD host-guest complexes with several dyes as guest molecules. Singular value decomposition (SVD) was used to select the chemical model and reduce noise. Molecular modeling provided the ability to predict the guest conformation-orientation (posing) within the cavity of β-CD and the nature of the involved interactions. Among those dyes showing observable spectral variation, the stoichiometric ratio of β-CD: dye (and log Kf) of methyl orange, fluorescein, phenol red, 4-(2-pyridylazo) resorcinol (PAR), and crystal violet were calculated to be 1:1 (4.26±0.01), 1:1 (1.53±0.08), 1:1 (3.11±0.04), 1:1 (1.06±0.12), and 2:1 (5.27±0.03), respectively. Compared with the classical method of titration, this method is simple and fast and has the advantage of needing reduced human interference. Molecular modeling facilitates a better understanding of the type of interactions and conformation of guest molecules in the β-CD cavity. The details of the proposed method are discussed in this paper. PMID:27111153

  3. Thermodynamic study of β-cyclodextrin-dye inclusion complexes using gradient flow injection technique and molecular modeling

    NASA Astrophysics Data System (ADS)

    Izadmanesh, Y.; Ghasemi, Jahan B.

    2016-08-01

    Gradient flow injection technique-diode array spectrophotometry was applied for β-cyclodextrin (β-CD)-dye inclusion complex studies. A single injection of a small amount of mixed β-CD-dye solution (100 μl) into the carrier solution of the dye and recording the spectra gave the titration data. The mole ratio data were calculated by calibrating the dispersion pattern using a calibrator dye (rose bengal). Model-based multivariate methods were used to analyze the spectral-mole ratio data and, as a result, estimate stability constants and concentration-spectral profiles. Reliability was tested by applying this method to study the β-CD host-guest complexes with several dyes as guest molecules. Singular value decomposition (SVD) was used to select the chemical model and reduce noise. Molecular modeling provided the ability to predict the guest conformation-orientation (posing) within the cavity of β-CD and the nature of the involved interactions. Among those dyes showing observable spectral variation, the stoichiometric ratio of β-CD: dye (and log Kf) of methyl orange, fluorescein, phenol red, 4-(2-pyridylazo) resorcinol (PAR), and crystal violet were calculated to be 1:1 (4.26 ± 0.01), 1:1 (1.53 ± 0.08), 1:1 (3.11 ± 0.04), 1:1 (1.06 ± 0.12), and 2:1 (5.27 ± 0.03), respectively. Compared with the classical method of titration, this method is simple and fast and has the advantage of needing reduced human interference. Molecular modeling facilitates a better understanding of the type of interactions and conformation of guest molecules in the β-CD cavity. The details of the proposed method are discussed in this paper.

  4. Time-dependent sorption of norflurazon in four different soils: use of beta-cyclodextrin solutions for remediation of pesticide-contaminated soils.

    PubMed

    Villaverde, Jaime

    2007-04-01

    High pesticide concentrations in soil from spills or discharges can result in point-source contamination of ground and surface waters. Cost-effective technologies are needed for on-site treatment that meet clean-up goals and restore soil function. Remediation is particularly challenging when a mixture of pesticides is present. beta-Cyclodextrins (BCD) solutions are employed to enhance the aqueous solubility of a hydrophobic organic compound. The interaction of norflurazon (NFL) with BCD yielded the formation of inclusion complexes at a 1:1 stoichiometric ratio in solution. The change of the sorption parameter K(d) as affected by the time, and desorption studies of NFL previously adsorbed on four different soils with different characteristics have been performed in the presence of 0.01 M BCD or 0.01 M Ca(NO(3))(2) acting as extractant solutions. NFL sorption increased with the residence time in soil, making it more resistant to be desorbed. Likewise, leaching experiments were performed in packed soil columns eluting initially with distilled water, with the aim to simulate the herbicide drainflow losses because of rainfall, approaching to a more realistic environment, and later with 0.01 M BCD solutions to extract the residual NFL bound. The results showed that removal efficiencies of the different flushing systems were significantly influenced by their affinity and selectivity for the contaminants in the soil matrix as well as BCD adsorption on soils, since this could act like a bridge between pesticide molecule and soil particles increasing the stay of NFL in soil. These results are further information to be in condition to predict the potential effect of the BCD solutions on soil chemical decontamination in the field situation assessing the likelihood for bioremediation of a pesticide contaminated-soil, since the increasing in hydrosolubility of the contaminants means the first step before microorganism uptaken. PMID:16973265

  5. New enzymatically polymerized copolymers from 4-tert-butylphenol and 4-ferrocenylphenol and their modification and inclusion complexes with β-cyclodextrin

    PubMed Central

    Mondrzyk, Adam; Mondrzik, Beate; Gingter, Sabrina

    2012-01-01

    Summary The enzymatically catalyzed synthesis of a copolymer of 4-tert-butylphenol and 4-ferrocenylphenol by horse radish peroxidase (HRP) in the presence of H2O2 in a 1,4-dioxane/water system is described. Furthermore, polymer-analogous alkylation of the free hydroxy groups and subsequent click reaction with mono-6-azido-6-desoxy-β-cyclodextrin (N3-β-CD) was carried out. The formation of inter- and intramolecular inclusion complexes was investigated by DLS measurement. PMID:23243473

  6. New enzymatically polymerized copolymers from 4-tert-butylphenol and 4-ferrocenylphenol and their modification and inclusion complexes with β-cyclodextrin.

    PubMed

    Mondrzyk, Adam; Mondrzik, Beate; Gingter, Sabrina; Ritter, Helmut

    2012-01-01

    The enzymatically catalyzed synthesis of a copolymer of 4-tert-butylphenol and 4-ferrocenylphenol by horse radish peroxidase (HRP) in the presence of H(2)O(2) in a 1,4-dioxane/water system is described. Furthermore, polymer-analogous alkylation of the free hydroxy groups and subsequent click reaction with mono-6-azido-6-desoxy-β-cyclodextrin (N(3)-β-CD) was carried out. The formation of inter- and intramolecular inclusion complexes was investigated by DLS measurement. PMID:23243473

  7. Solid-state characterization of sertraline base-β-cyclodextrin inclusion complex.

    PubMed

    Ogawa, Noriko; Hashimoto, Takuro; Furuishi, Takayuki; Nagase, Hiromasa; Endo, Tomohiro; Yamamoto, Hiromitsu; Kawashima, Yoshiaki; Ueda, Haruhisa

    2015-03-25

    Sertraline is one of the serotonin-specific reuptake inhibitors that is effective in treating several disorders such as major depression, obsessive-compulsive disorder, panic disorder, and social phobia. It is marketed in the form of its hydrochloride salt, which exhibits better solubility in water than its free base form. However, the absorption of sertraline through biological membranes could be improved by enhancing the solubility of its base because it is more hydrophobic than sertraline hydrochloride. To clarify the mechanism for the interaction of sertraline base with β-CD, it is important to study the basic interaction between the β-CD ring and sertraline base. Therefore, in this study, the currently used hydrochloride salt form was converted into the free base and β-CD was used as a model for β-CD derivatives to evaluate the interaction between β-CD and the sertraline base. The solid-state physicochemical characteristics of the sertraline-β-CD complex were investigated by the phase solubility method, differential scanning calorimetry, Fourier transform IR spectroscopy, FT-Raman spectroscopy, powder X-ray diffraction, and (13)C cross-polarization magic-angle spinning NMR measurements. The results showed that sertraline base and β-CD form an inclusion complex, and the stoichiometric ratio of the solid-state sertraline base-β-CD complex is 1:1, which was estimated by the (1)H NMR measurements of the complex dissolved in DMSO-d6. PMID:25637819

  8. Enzyme coated beta-cyclodextrin for effective adsorption and glucose-responsive closed-loop insulin delivery.

    PubMed

    Anirudhan, T S; Nair, Anoop S; Nair, Syam S

    2016-10-01

    Inconsistent dosage of insulin (INS) for type 2 diabetes patients lead to severe adverse effects like limb amputation, blindness and fatal hypo or hyper glycaemia. Hence, a drug delivery system (DDS) capable of consistent INS release by sensing changes in blood glucose level is essential. Herein, we report a glucose responsive DDS comprised of oleic acid-grafted-aminated beta cyclodextrin (OA-g-ACD) copolymer, coated with a dispersion of glucose oxidase (GOx) and catalase (CAT). The prepared DDS was characterised using FTIR, Optical Microscopy, H(1) NMR, DLS and SEM. Hydrophobicity and drug loading capacity was ascertained using contact angle measurements and confocal laser scanning microscopy (CLSM) respectively. Extent of swelling was observed to be a function of glucose concentration. INS release profile showed a cumulative release of 78.0 % after 240min. Flow cytometry studies revealed greater population of INS on HeLa cells indicating application of DDS as potential candidate for the intravenous administration of INS. PMID:27296445

  9. [Pharmacological studies on the clathrate compound of mobenzoxamine with beta-cyclodextrin. (I). Effects on the digestive system].

    PubMed

    Yokochi, E; Kohno, S; Ohata, K

    1988-11-01

    Effects of the clathrate compound of mobenzoxamine (MBX) with beta-cyclodextrin (MBX-CD), a new gastro-intestinal function modulator, on the digestive system were studied in comparison with those of metoclopramide, domperidone and trimebutine. MBX-CD showed inhibitory effects that were approximately 1/4 times as potent as metoclopramide on both apomorphine- and copper sulfate-induced emesis and about 1/40 times as potent as domperidone on apomorphine-induced emesis in dogs. In rats, MBX-CD enhanced gastric emptying as potently as metoclopramide, and only MBX-CD showed a clear amelioration of the delayed gastric emptying induced by BaCl2. Similarly, only MBX-CD showed an ameliorative effect on small intestinal transport accelerated by BaCl2 in mice. Though both MBX and trimebutine inhibited spontaneous contractions of the isolated guinea pig stomach and rabbit intestine, it seemed that the properties of these effects were different from those of papaverine. On isolated guinea pig ileum, MBX inhibited contractions induced by various agonists equally to or more potently than trimebutine or papaverine. The results suggest that MBX-CD or MBX acts extensively on the gastro-intestinal system for the reason that it has not only the respective properties of the gastro-intestinal function modulators used as the standards, but also its own characteristic effects. PMID:3243512

  10. Antiproliferative effect of methyl-beta-cyclodextrin in vitro and in human tumour xenografted athymic nude mice.

    PubMed Central

    Grosse, P. Y.; Bressolle, F.; Pinguet, F.

    1998-01-01

    The anti-tumour activity of methyl-beta-cyclodextrin (MEBCD), a cyclic oligosaccharide known for its interaction with the plasma membrane, was investigated in vitro and in vivo and compared with that of doxorubicin (DOX) in the human tumour models MCF7 breast carcinoma and A2780 ovarian carcinoma. In vitro proliferation was assessed using the MTT assay. In vivo studies were carried out using xenografted Swiss nude mice injected weekly i.p. with MEBCD at 300 or 800 mg kg(-1) or DOX at 2 mg kg(-1), during 2 months. Under these conditions, MEBCD was active against MCF7 and A2780 cell lines and tumour xenografts. For each tumour model, the tumoral volume of the xenografted mice treated with MEBCD was at least twofold reduced compared with the control group. In the MCF7 model, MEBCD (800 mg kg(-1)) was more active than DOX (2 mg kg(-1)). After 56 days of treatment with MEBCD, no toxicologically meaningful differences were observed in macroscopic and microscopic parameters compared with controls. The accumulation of MEBCD in normal and tumour tissues was also assessed using a chromatographic method. Results indicated that after a single injection of MEBCD, tumour, liver and kidneys accumulated the highest concentrations of MEBCD. These results provided a basis for the potential therapeutic application of MEBCD in cancer therapy. PMID:9820174

  11. Enhanced dissolution, stability and physicochemical characterization of ATRA/2-hydroxypropyl-β-cyclodextrin inclusion complex pellets prepared by fluid-bed coating technique.

    PubMed

    Chen, Zhongjian; Lu, Yi; Qi, Jianping; Wu, Wei

    2013-02-01

    The aim of this work was to prepare stable all-trans-retinoic acid (ATRA)/2-hydroxypropyl-β-cyclodextrin (HPCD) inclusion complex pellets with industrial feasible technology, the fluid-bed coating technique, using PVP K30 simultaneously as binder and reprecipitation retarder. The coating process was fluent with high coating efficiency. In vitro dissolution of the inclusion complex pellets in 5% w/v Cremopher EL solution was dramatically enhanced with no reprecipitation observed, and significantly improved stability against humidity (92.5% and 75% RH) and illumination (4500 lx ± 500 lx) was achieved by HPCD inclusion. Differential scanning calorimetry and powder X-ray diffractometry confirmed the absence of crystallinity of ATRA. Fourier transform-infrared spectrometry revealed interaction between ATRA and HPCD adding evidence on inclusion of ATRA moieties into HPCD cavities. Solid-state (13)C NMR spectrometry indicated possible inclusion of ATRA through the polyene chain, which was the main reason for the enhanced photostability. It is concluded that the fluid-bed coating technique has the potential use in the industrial preparation of ATRA/HPCD inclusion complex pellets. PMID:22304703

  12. Folate-conjugated beta-cyclodextrin-based polymeric micelles with enhanced doxorubicin antitumor efficacy.

    PubMed

    Zhang, Lu; Lu, Jiafei; Jin, Yangmin; Qiu, Liyan

    2014-10-01

    In order to enhance the antitumor effects of doxorubicin (DOX), a novel micellar vector with high DOX loading and tumor targeting function based on folate-conjugated amphiphilic copolymer folate-poly(ethylene glycol)-poly(d,l-lactide)-β-cyclodextrin (FA-PEL-CD) was constructed. Cytotoxicity and cellular uptake experiments were performed in HeLa, KB, and A549 cell lines expressing different amounts of folate receptors in order to evaluate the targeting effect of the folate modification. The antitumor experiments performed in a KB cell-xenografted nude mouse model showed that the treatment with 10mg/kg DOX loaded FA-PEL-CD micelles achieved approximately 86% of tumor growth inhibition compared to the control. Ex vivo fluorescence imaging experiments and histological examination confirmed that folate modification can enhance the antitumorigenesis efficacy and reduce the cardiotoxicity of DOX. These results suggest that FA-PEL-CD copolymer-based micelles are promising nanocarriers for targeted doxorubicin delivery, with improved antitumor efficacy and reduced toxicity in normal tissues. PMID:25058857

  13. Preparation, characterization and pharmacokinetics of doxycycline hydrochloride and florfenicol polyvinylpyrroliddone microparticle entrapped with hydroxypropyl-β-cyclodextrin inclusion complexes suspension.

    PubMed

    Li, Xianqiang; Xie, Shuyu; Pan, Yuanhu; Qu, Wei; Tao, Yanfei; Chen, Dongmei; Huang, Lingli; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2016-05-01

    In order to effectively control the bacterial pneumonia in pigs, doxycycline hydrochloride (DoxHcl) and florfenicol (FF) microparticle suspension together with inclusion complexes was prepared by using hydroxypropyl-β-cyclodextrin (HP-β-CD) as host molecules, polyvinylpyrroliddone (PVP) as polymer carriers and hydroxypropyl methyl cellulose (HPMC) as suspending agents. In vitro antibacterial activity, properties, stability and pharmacokinetics of the suspension were studied. The results demonstrated that DoxHcl and FF had a synergistic or additive antibacterial activity against Streptococcus suis, Actinobacillus pleuropneumoniae and Haemophilus parasuis. The size, polydispersity index and zeta potential of microparticles were 1.46 ± 0.06 μm, 0.30 ± 0.02 and 1.53 ± 0.04 mV, respectively. The encapsulation efficiency (EE) of DoxHcl and FF was 45.28% ± 3.30% and 89.69% ± 2.71%, respectively. The re-dispersed time and sedimentation rate of the suspension were 1 min and 1. The suspension went through the 9-gage needle smoothly with withdrawal volume of 9.12 ± 0.87 mL/min. The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration to pig, DoxHcl and FF could maintain over 0.15 μg/mL for 72 h. Compared to the control injection, the suspension increased the elimination half-life (T½ke) as well as mean residence time (MRT) of DoxHcl from 5.73 to 9.77 h and from 12.02 to 18.81 h, and those of FF from 12.02 to 26.19 h and from 12.02 to 28.16 h, respectively. The suspension increased the bioavailability of DoxHcl and FF by 1.74 and 1.13-fold, respectively. These results suggest that the compound suspension is a promising formulation for pig pneumonia therapy. PMID:26918512

  14. Enhanced stability of a naringenin/2,6-dimethyl β-cyclodextrin inclusion complex: molecular dynamics and free energy calculations based on MM- and QM-PBSA/GBSA.

    PubMed

    Sangpheak, Waratchada; Khuntawee, Wasinee; Wolschann, Peter; Pongsawasdi, Piamsook; Rungrotmongkol, Thanyada

    2014-05-01

    The structure, dynamic behavior and binding affinity of the inclusion complexes between naringenin and the two cyclodextrins (CDs), β-CD and its 2,6-dimethyl derivative (DM-β-CD), were theoretically studied by multiple molecular dynamics simulations and free energy calculations. Naringenin most likely prefers to bind with CDs through the phenyl ring. Although a lower hydrogen bond formation of naringenin with the 3-hydroxyl group of DM-β-CD (relative to β-CD) was observed, the higher cavity could encapsulate almost the whole naringenin molecule. In contrast for the naringenin/β-CD complex, the phenyl ring feasibly passed through the primary rim resulting in the chromone ring binding inside instead. MM-PBSA/GBSA and QM-PBSA/GBSA binding free energies strongly suggested a greater stability of the naringenin/DM-β-CD inclusion complex. Van der Waals force played an important role as the key guest-host interaction for the complexation between naringenin and each cyclodextrin. PMID:24681901

  15. Electrochemical and surface plasmon resonance characterization of β-cyclodextrin-based self-assembled monolayers and evaluation of their inclusion complexes with glucocorticoids

    NASA Astrophysics Data System (ADS)

    Frasconi, Marco; Mazzei, Franco

    2009-07-01

    This paper describes the characterization of a self-assembled β-cyclodextrin (β-CD)-derivative monolayer (β-CD-SAM) on a gold surface and the study of their inclusion complexes with glucocorticoids. To this aim the arrangement of a self-assembled β-cyclodextrin-derivative monolayer on a gold surface was monitored in situ by means of surface plasmon resonance (SPR) spectroscopy and double-layer capacitance measurements. Film thickness and dielectric constant were evaluated for a monolayer of β-CD using one-color-approach SPR. The selectivity of the β-CD host surface was verified by using electroactive species permeable and impermeable in the β-CD cavity. The redox probe was selected according to its capacity to permeate the β-CD monolayer and its electrochemical behavior. In order to evaluate the feasibility of an inclusion complex between β-CD-SAM with some steroids such as cortisol and cortisone, voltammetric experiments in the presence of the redox probes as molecules competitive with the steroids have been performed. The formation constant of the surface host-guest by β-CD-SAM and the steroids under study was calculated.

  16. Preparation, physicochemical analysis and molecular modeling investigation of 2,2‧-Bipyridine: β-Cyclodextrin inclusion complex in solution and solid state

    NASA Astrophysics Data System (ADS)

    Periasamy, R.; Kothainayaki, S.; Sivakumar, K.

    2015-11-01

    Supramolecular interaction between 2,2‧-Bipyridine (BPY) and β-Cyclodextrin (β-CD) has been investigated in solution and solid state. Non-covalent interaction between BPY and β-CD was studied in solution using absorption and fluorescence spectroscopy. Inclusion complex of BPY and β-CD was prepared in solid state by co-precipitation method and it was characterized using Fourier Transform Infra-red spectroscopy (FT-IR), Thermal analysis, Scanning Electron Microscopy (SEM), Powder X-ray diffractometry (XRD) and Atomic Force Microscopy (AFM). Binding constant values and 1:1 stoichiometry of the inclusion complex were calculated using Benesi-Hildebrand plots at 303 K. Using continuous variation method the 1:1 stoichiometry has been confirmed for BPY: β-CD complex. Thermodynamic parameter, ΔG of inclusion complex formation was determined and the negative value indicated that the inclusion process was an exergonic and spontaneous process. The most probable model of BPY: β-CD inclusion complex suggested by molecular docking studies was in good agreement with the results obtained by experimental methods.

  17. 1H NMR studies of maltose, maltoheptaose, alpha-, beta-, and gamma-cyclodextrins, and complexes in aqueous solutions with hydroxy protons as structural probes.

    PubMed

    Bekiroglu, Somer; Kenne, Lennart; Sandström, Corine

    2003-03-01

    The (1)H NMR chemical shifts, coupling constants, temperature coefficients, and exchange rates have been measured for the hydroxy protons of aqueous solutions of alpha-, beta-, and gamma-cyclodextrins, maltose, and maltoheptaose. In cyclodextrins (CDs), the high chemical shift of the O(3)H signal and its small (3)J(OH,CH) value suggest that O(3)H is involved in a hydrogen bond. The small temperature coefficients and rate of exchange values of O(2)H and O(3)H confirm the involvement of O(3)H in hydrogen bonding and indicate that O(2)H is the hydrogen bond partner. In maltose, two distinct NMR signals with two different vicinal coupling constants are found for O(2')H. A cross-peak in the ROESY spectrum indicates chemical exchange between the O(2')H and O(3)H protons. The existence of two distinct NMR signals with different J values for O(2')H shows the influence of anomeric configuration on the O(2')H-O(3)H interaction. The effect of complexation with methyl benzoate, adamantane-1-carboxylic acid, adamantane-1-ol, and l- and d-tryptophane on the NMR spectra of the hydroxy protons of alpha-, beta-, and gamma-cyclodextrins and of maltose has been investigated. No significant spectral changes were observed upon addition of methyl benzoate and adamantane-1-carboxylic acid. The addition of adamantane-1-ol resulted in an upfield shift and a strong broadening of the O(2)H signal from alpha-CD, and a small temperature coefficient was measured upon complexation. The O(2)H and O(3)H signals in beta-CD were broadened and shifted downfield upon addition of l- and d-tryptophane. PMID:12608778

  18. Enhanced rectal absorption and reduced local irritation of the anti-inflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble beta-cyclodextrin derivatives and formulation as oleaginous suppository.

    PubMed

    Arima, H; Kondo, T; Irie, T; Uekama, K

    1992-11-01

    To improve the rectal delivery of ethyl 4-biphenylylacetate (EBA), a prodrug of the anti-inflammatory drug 4-biphenylylacetic acid (BPAA), the use of highly water-soluble 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CyD) was investigated and compared with the use of the parent beta-cyclodextrin (beta-CyD). Among the three beta-CyDs, HP-beta-CyD was best at improving the rectal bioavailability of EBA in rats after single and multiple administrations of oleaginous suppositories (Witepsol H-5) containing the complexes. To gain insight into the enhancing effect of beta-CyDs, the absorption behaviors of EBA (observed by monitoring BPAA as an active metabolite of EBA) and beta-CyDs themselves were examined in vitro, in situ, and in vivo. The in situ recirculation study revealed that the complexed form of EBA was less absorbable from the rectal lumen in the solution state, but this disadvantageous effect of beta-CyDs was compensated in part by the inhibition of the bioconversion of EBA to BPAA. When beta-CyDs were coadministered with EBA in vivo, however, rather high amounts of HP-beta-CyD (approximately 26% of dose) and DM-beta-CyD (approximately 21% of dose), compared with beta-CyD (approximately 5% of dose), were absorbed from the rat rectum. Thus, the enhancement of rectal absorption of EBA in vivo can be explained by the facts that the hydrophilic beta-CyDs increased the release rate of EBA from the vehicle and stabilized EBA in the rectal lumen and that the drug was partly absorbed in the form of the complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1447717

  19. The influence of dissolved H2O content in supercritical carbon dioxide to the inclusion complexes formation of ketoprofen/β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Goenawan, Joshua; Trisanti, P. N.; Sumarno

    2015-12-01

    This work studies the relation between dissolved H2O content in supercritical carbon dioxide (SC-CO2) with the formation of ketoprofen (KP)/β-cyclodextrin(CD) inclusion complexes. The process involves a physical mixture of these two compounds into contact with the supercritical carbon dioxide which had been previously saturated with H2O over a certain duration. The pressure used for saturation process is 130 bar and saturation temperature was ranged between 30 °C to 50 °C. The inclusion process was achieved by keeping it for 2 hours at 160 bar and 200 bar with inclusion temperature of 50 °C. The results enable us to suggest explanations for the inclusion formation. The inclusion complexes can be formed by contacting the dissolved H2O in SC-CO2 to the physical mixture of KP and CD. An increase in the temperature of saturation process resulted in an increase of dissolved H2O content in the supercritical carbon dioxide. The increasing levels of this water soluble resulted an increase in the inclusion complexes that has been formed. The formation of inclusion complexes includes the water molecules enhancing the emptying of the CD cavities and being replaced by KP, towards a more stable energy state. The drug release used for analyzing the dissolution rate of the KP/CD complexes. The results vary from 79,85% to 99,98% after 45 minutes which is above the rate that has been assigned by Farmakope Indonesia at 70% dissolution rate for KP. The use of SC-CO2 offers a new methods for increasing the rate of dissolution of drugs that are hydrophobic such as KP. CO2 used as a supercritical fluid because of its relatively low cost, easily obtainable supercritical conditions, and lack of toxicity. The material samples were characterized by DSC and Spectrophotometer UV-vis technique.

  20. Entropy-controlled supramolecular photochirogenesis: enantiodifferentiating Z-E photoisomerization of cyclooctene included and sensitized by permethylated 6-O-modified beta-cyclodextrins.

    PubMed

    Fukuhara, Gaku; Mori, Tadashi; Wada, Takehiko; Inoue, Yoshihisa

    2006-10-13

    Permethylated 6-O-modified beta-cyclodextrins 2a-2d were synthesized as novel photosensitizing hosts with a flexible skeleton. Circular dichroism (CD) and 2D NMR spectral examinations of benzoate 2a revealed that the benzoate moiety is deeply included into its own cavity in aqueous solution. Upon addition of (Z)-cyclooctene (1Z) to a 50% aqueous methanol solution of 2a at 25 degrees C, the benzoate moiety of 2a was gradually excluded from the cavity as indicated by the CD spectral changes; the Job's plot revealed the formation of a 1:1 complex of 2a with 1Z. The binding constants for the complexation of 1Z by 2a were determined by CD spectral titration in 50% aqueous methanol at various temperatures. The van't Hoff analysis of the obtained data afforded the thermodynamic parameters (DeltaH degrees = -3.1 kJ mol(-1), DeltaS degrees = 48.5 J mol(-1) K(-1)), demonstrating the entropy-driven complexation by the permethylated cyclodextrin. This is in sharp contrast to the complexation of 1Z by nonmethylated beta-cyclodextrin benzoate that is driven by enthalpy (DeltaH degrees = -31.8 kJ mol(-1) and DeltaS degrees = -51.1 J mol(-1) K(-1)). Upon supramolecular photosensitization with 2a-2d, 1Z isomerized to the (E)-isomer (1E) in moderate enantiomeric excesses (ee's), which however displayed significant temperature dependence with accompanying switching of the product's chirality in an extreme case. Such dynamic behavior of ee is very different from that reported for the photosensitization with nonmethylated cyclodextrin benzoate, where the product's ee is controlled by host occupancy. Eyring treatment of the ee obtained at various temperatures (<0 degrees C) gave the differential activation parameters for the enantiodifferentiation process occurring in the supramolecular exciplex, revealing the crucial role of entropy, as indicated by the DeltaDeltaS(++) value changing dynamically from +4 to -24 J K(-1) mol(-1). The origin of the contrasting behavior of permethylated

  1. Solid inclusion complexes of oleanolic acid with amino-appended β-cyclodextrins (ACDs): Preparation, characterization, water solubility and anticancer activity.

    PubMed

    Ren, Yufeng; Liu, Ying; Yang, Zhikuan; Niu, Raomei; Gao, Kai; Yang, Bo; Liao, Xiali; Zhang, Jihong

    2016-12-01

    Oleanolic acid (OA) is a pentacyclic triterpenoid acid of natural abundance in plants which possesses important biological activities. However, its medicinal applications were severely impeded by the poor water solubility and resultant low bioavailability and potency. In this work, studies on solid inclusion complexes of OA with a series of amino-appended β-cyclodextrins (ACDs) were conducted in order to address this issue. These complexes were prepared by suspension method and were well characterized by NMR, SEM, XRD, TG, DSC and Zeta potential measurement. The 2:1 inclusion mode of ACDs/OA complexes was elucidated by elaborate 2D NMR (ROESY). Besides, water solubility of OA was dramatically promoted by inclusion complexation with ACDs. Moreover, in vitro anticancer activities of OA against human cancer cell lines HepG2, HT29 and HCT116 were significantly enhanced after formation of inclusion complexes, while the apoptotic response results indicated their induction of apoptosis of cancer cells. This could provide a novel approach to development of novel pharmaceutical formulations of OA. PMID:27612690

  2. Transdermal delivery of the in situ hydrogels of curcumin and its inclusion complexes of hydroxypropyl-β-cyclodextrin for melanoma treatment.

    PubMed

    Sun, Yunbo; Du, Lina; Liu, Yangpu; Li, Xin; Li, Miao; Jin, Yiguang; Qian, Xiaohong

    2014-07-20

    Curcumin (Cur) is a hydrophobic polyphenol with diverse pharmacological effects, especially for cancer treatment. However, its weak water solubility and stability was the major obstacle for the formulation research of Cur. The complexation of Cur and hydroxypropyl-β-cyclodextrin (HP-β-CD) was done by grinding. The increasing solubility of Cur was achieved due to complexation and the photochemical stability of Cur was improved. The inclusion of Cur could happen when two ends of Cur were embedded into the cavity of the HP-β-CD rings. The in situ hydrogels (ISGs) of Cur and its inclusion complexes were prepared using poloxamers 407 and 188 as the matrix. The extent of drug's in vitro release from the ISGs depended on the dissolution of drugs. Both of the ISGs had transdermal effect and cytotoxicity on B16-F10 cells. However, the effects of the ISGs containing Cur inclusion complexes were much higher than those of Cur ISGs because of the improved Cur solubility in the former. The cytotoxicity of Cur on melanoma cells was related to blocking of cellular proliferation in the G2/M stage followed by cellular apoptosis. The ISGs of Cur inclusion complexes are a promising formulation for melanoma treatment. PMID:24746691

  3. beta-Cyclodextrin derivatives as carriers to enhance the antiviral activity of an antisense oligonucleotide directed toward a coronavirus intergenic consensus sequence.

    PubMed

    Abdou, S; Collomb, J; Sallas, F; Marsura, A; Finance, C

    1997-01-01

    The ability of cyclodextrins to enhance the antiviral activity of a phosphodiester oligodeoxynucleotide has been investigated. A 18-mer oligodeoxynucleotide complementary to the initiation region of the mRNA coding for the spike protein and containing the intergenic consensus sequence of an enteric coronavirus has been tested for antiviral action against virus growth in human adenocarcinoma cells. The phosphodiester oligodeoxynucleotide only showed a limited effect on virus growth rate (from 12 to 34% viral inhibition in cells treated with 7.5 to 25 microM oligodeoxynucleotide, respectively, at a multiplicity of infection of 0.1 infectious particle per cell). In the same conditions, the phosphorothioate analogue exhibited stronger antiviral activity, the inhibition increased from 56 to 90%. The inhibitory effect of this analogue was antisense and sequence-specific. Northern blot analysis showed that the sequence-dependent mechanism of action appears to be the inhibition of mRNA transcription. We conclude that the coronavirus intergenic consensus sequence is a good target for an antisense oligonucleotide antiviral action. The properties of the phosphodiester oligonucleotide was improved after its complexation with cyclodextrins. The most important increase of the antiviral activity (90% inhibition) was obtained with only 7.5 microM oligonucleotide complexed to a cyclodextrin derivative, 6-deoxy-6-S-beta-D-galactopyranosyl-6-thio-cyclomalto-heptaose+ ++ in a molar ratio of 1:100. These studies suggest that the use of cyclodextrin derivatives as carrier for phosphodiester oligonucleotides delivery may be an effective method for increasing the therapeutic potential of these compounds in viral infections. PMID:9672621

  4. Selective detergent-extraction from mixed detergent/lipid/protein micelles, using cyclodextrin inclusion compounds: a novel generic approach for the preparation of proteoliposomes.

    PubMed Central

    Degrip, W J; Vanoostrum, J; Bovee-Geurts, P H

    1998-01-01

    A novel generic approach is described for the selective extraction of detergents from mixed detergent/lipid/protein micelles for the preparation of proteoliposomes of defined lipid-protein ratio. The approach is based on the much higher affinity of inclusion compounds of the cyclodextrin type for detergents in comparison with bilayer-forming lipids. This approach has distinct advantages over other procedures currently in use. It produces good results with all detergents tested, independent of type and critical micelle concentration, and appears to be generally applicable. It yields nearly quantitative recovery of membrane protein in the proteoliposome fraction. Finally, no large excess of lipid is required; a molar ratio of lipid to protein of 100 to 1 already produces proteoliposomes with functional membrane protein, but higher ratios are well tolerated. The size of the vesicles thus obtained depends on the detergent used. Separation of the resulting proteoliposomes from the detergent-cyclodextrin complexes was most easily achieved by centrifugation through a discontinuous sucrose gradient. A variety of detergents was tested in this procedure on the bovine rod visual pigment rhodopsin in combination with retina lipids. In all cases good yields of proteoliposomes were obtained, which contained fully functional rhodopsin. PMID:9480873

  5. A New Approach for Quantitative Determination of γ-Cyclodextrin in Aqueous Solutions: Application in Aggregate Determinations and Solubility in Hydrocortisone/γ-Cyclodextrin Inclusion Complex.

    PubMed

    Saokham, Phennapha; Loftsson, Thorsteinn

    2015-11-01

    Fast and simple high-pressure liquid chromatographic (HPLC) method with charged aerosol detector (CAD) was developed for quantitation of γ-cyclodextrin (γCD) in aqueous solutions. The chromatographic system consisted of a C18 column (i.e., the stationary phase) and an aqueous mobile phase containing 7% (v/v) methanol. Calibration curve was obtained over the γCD concentration range of 0.005%-1% (w/v). The limit of detection and quantitation of γCD were 0.0001% and 0.0002% (w/v), respectively. Formation of γCD aggregates in aqueous solution and their critical aggregation concentration (cac) were determined by both conventional dynamic light scattering method and permeation method using HPLC-CAD for quantitative determination of γCD. The cac of γCD was determined to be 0.95% (w/v) and the amount of γCD self-aggregates increased with increasing γCD concentrations. Also, the developed HPLC-CAD method was used to determine the γCD phase-solubility profile in an aqueous hydrocortisone (HC)/γCD complexation medium. The maximum concentration of dissolved γCD and HC was determined to be 1.47% and 0.31% (w/v), respectively. The membrane permeation method was shown to be a reliable method for determination of metastable γCD aggregates. The HPLC-CAD method was successfully applied for quantitative determination of γCD in aqueous solutions during permeation and phase-solubility studies. PMID:26249751

  6. Cationic-modified cyclodextrin nanosphere/anionic polymer as flocculation/sorption systems.

    PubMed

    Xiao, Huining; Cezar, Norlito

    2005-03-15

    Simultaneous removal of dissolved and colloidal substances has been a challenging task. The cationic-modified beta-cyclodextrin nanospheres synthesized in this work, in conjunction with a water-soluble polyacrylamide-based anionic polymer, potentially provide a novel approach to address the problem. The cyclodextrin was rendered cationic using (2,3-epoxypropyl)trimethylammonium chloride as a reagent. The cationicity of the modified cyclodextrin and the reaction between cyclodextrin and the reagent were characterized by electrophoresis measurement, polyelectrolyte titration, and NMR. As a dual-component flocculation system, the cationic cyclodextrin/anionic polymer significantly induced clay flocculation, lowering the relative turbidity of the clay suspension over a wide pH range. Meanwhile, as a nanospherical absorbent, the modified cyclodextrins exhibited strong affinity toward aromatic compounds via inclusion complex formation in the hydrophobic cavities, which was monitored by UV spectroscopy. These systems facilitated the simultaneous removal of dissolved and colloidal substances, which was unachievable previously. In addition, the interaction between anionic polymers and the clay particles pretreated with cationic cyclodextrin was investigated in order to reveal the flocculation mechanism. PMID:15721912

  7. Influence of Single Skimmer Versus Dual Funnel Transfer on the Appearance of ESI-Generated LiCl Cluster/ß-Cyclodextrin Inclusion Complexes.

    PubMed

    Kellner, Ina D; Drewello, Thomas

    2015-08-01

    Singly and doubly charged adducts of LiCl with β-cyclodextrin (βCD) of the type (βCD)(LiCl)(n)Li(+) and (βCD)2(LiCl)(p)Li2(2+) were studied using electrospray ionization mass spectrometry (ESI-MS). Insight into their structural composition was gained by analysis of their collision-induced dissociation (CID) mass spectra. The conditions the ions experience in the transfer region interfacing the ESI source and the mass analyzer were found to have a marked influence on the nature of the detected ions. In one instrument incorporating a single skimmer, individually attached LiCl ion pairs were observed, whereas the dual funnel ion guides of the second instrument allow the detection of previously unknown labile inclusion complexes of (LiCl)n clusters in βCD. PMID:25895893

  8. Spectroscopic investigation of the three prototropic forms of a β-cyclodextrin-indolizine derivative from its inclusion-cum-charge-transfer complexes

    NASA Astrophysics Data System (ADS)

    Ghosh, Bankim Chandra; Deb, Nipamanjari; Becuwe, Matthieu; Fourmentin, Sophie; Mukherjee, Asok K.

    2011-02-01

    By absorption and fluorescence (steady state and time-resolved) studies, three prototropic forms of (N-6-deoxy-β-cyclodextrin-6-yl-1-aminocarbonyl)-3-(4-fluorobenzoyl)-7-pyridine-4-yl indolizine, (1) have been established and shown to be a potential fluorescent pH sensor with switching action. Inclusion complexes of (1) with a number of quinones have been shown to exhibit charge transfer (CT) spectra in aqueous medium and variation of such spectra with change in pH yield the proton affinity of the biologically important indolizine moiety. Förster cycle reveals that in the excited state indolizine moiety has a greater proton affinity. The nature of the CT transitions (whether n-donor-π-acceptor or π-donor-π-acceptor) has been experimentally ascertained.

  9. Influence of Single Skimmer Versus Dual Funnel Transfer on the Appearance of ESI-Generated LiCl Cluster/ß-Cyclodextrin Inclusion Complexes

    NASA Astrophysics Data System (ADS)

    Kellner, Ina D.; Drewello, Thomas

    2015-08-01

    Singly and doubly charged adducts of LiCl with β-cyclodextrin (βCD) of the type (βCD)(LiCl)nLi+ and (βCD)2(LiCl)pLi2 2+ were studied using electrospray ionization mass spectrometry (ESI-MS). Insight into their structural composition was gained by analysis of their collision-induced dissociation (CID) mass spectra. The conditions the ions experience in the transfer region interfacing the ESI source and the mass analyzer were found to have a marked influence on the nature of the detected ions. In one instrument incorporating a single skimmer, individually attached LiCl ion pairs were observed, whereas the dual funnel ion guides of the second instrument allow the detection of previously unknown labile inclusion complexes of (LiCl)n clusters in βCD.

  10. Inclusion complexes of chloramphenicol with β-cyclodextrin and aminoacids as a way to increase drug solubility and modulate ROS production.

    PubMed

    Aiassa, Virginia; Zoppi, Ariana; Albesa, Inés; Longhi, Marcela R

    2015-05-01

    The aim of this study was to improve the solubility of chloramphenicol and reduce the production of reactive oxygen species (ROS) in leucocytes induced by this drug, using complexation. Multicomponent complexes were prepared by the addition of β-cyclodextrin with glycine or cysteine. Nuclear magnetic resonance and phase solubility studies provided information at the molecular level on the structure of the complexes and their association binding constants, respectively. In the solid state, all systems were extensively characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy, thermal analysis and X-ray powder diffraction. Antimicrobial activity of inclusion complexes was investigated by agar diffusion methods. Finally ROS determination by chemiluminescence was used to investigate the effect of complex formation on the potential toxicity in human leucocytes. These studies revealed that multicomponent complexes can increase the aqueous solubility of chloramphenicol as well as reducing the stress by ROS production in leucocytes and maintaining its microbiological activity. PMID:25659705

  11. Enhancing effect of hydroxypropyl-beta-cyclodextrin on cutaneous penetration and activation of ethyl 4-biphenylyl acetate in hairless mouse skin.

    PubMed

    Arima, H; Miyaji, T; Irie, T; Hirayama, F; Uekama, K

    1998-01-01

    The effect of hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) on the cutaneous penetration and activation of ethyl 4-biphenylyl acetate (EBA), a prodrug of non-steroidal anti-inflammatory drug 4-biphenylylacetic acid (BPAA), from hydrophilic ointment was investigated, using hairless mouse skin in vitro. When the hydrophilic ointment containing a complex of EBA with HP-beta-CyD was applied to the full-thickness skin, HP-beta-CyD facilitated the penetration of EBA into the skin, the conversion of EBA to BPAA in the epidermis and the transfer of BPAA to the receptor phase. Under the present condition, pre- and post-application of the ointment containing HP-beta-CyD onto the skin did not affect the cutaneous penetration of EBA and its activation. When the ointment containing the EBA:HP-beta-CyD complex was applied to the skin, the flux of BPAA through the tape-stripped skin was greater than that through the full-thickness skin, while the activation of the prodrug in the skin was slowed down by the tape-stripping. When propylene glycol was used as a vehicle, HP-beta-CyD no longer enhanced the cutaneous permeation of BPAA through the full-thickness skin. These results suggest that the enhancing effect of HP-beta-CyD on the cutaneous penetration of EBA would be ascribable largely to an increase in effective concentration of EBA in the ointment. Furthermore, the slow diffusion of EBA solubilized in HP-beta-CyD through the stratum corneum, together with the vehicle effect, could make the prodrug more susceptible to the metabolic process that is active in the epidermis, eventually leading to the facilitated activation of the prodrug. PMID:16256708

  12. Antiviral activity against the hepatitis C virus (HCV) of 1-indanone thiosemicarbazones and their inclusion complexes with hydroxypropyl-β-cyclodextrin.

    PubMed

    Glisoni, Romina J; Cuestas, María L; Mathet, Verónica L; Oubiña, José R; Moglioni, Albertina G; Sosnik, Alejandro

    2012-10-01

    The hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis in humans. Approximately 5% of the infected people die from cirrhosis or hepatocellular carcinoma. The current standard therapy comprises a combination of pegylated-interferon alpha and ribavirin. Due to the relatively low effectiveness, the prohibitive costs and the extensive side effects of the treatment, an intense research for new direct-acting anti-HCV agents is taking place. Furthermore, NS3 protease inhibitors recently introduced into the market are not effective against all HCV subgenotypes. Thiosemicarbazones (TSCs) have shown antiviral activity against a wide range of DNA and RNA viruses. However, their extremely low aqueous solubility and high self-aggregation tendency often preclude their reliable biological evaluation in vitro. In this work, we investigated and compared for the first time the anti-HCV activity of two 1-indanone TSCs, namely 5,6-dimethoxy-1-indanone TSC and 5,6-dimethoxy-1-indanone N4-allyl TSC, and their inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβ-CD) in Huh-7.5 cells containing the full-length and the subgenomic subgenotype 1b HCV replicon system. Studies of physical stability in culture medium showed that free TSCs precipitated rapidly and formed submicron aggregates. Conversely, TSC complexation with HPβ-CD led to more stable systems with minimal size growth and drug concentration loss. More importantly, both TSCs and their inclusion complexes displayed a potent suppression of the HCV replication in both cell lines with no cytotoxic effects. The mechanism likely involves the inhibition of non-structural proteins of the virus. In addition, findings suggested that the cyclodextrin released the drug to the culture medium over time. This platform could be exploited for the study of the drug toxicity and pharmacokinetics animal models. PMID:22885176

  13. Effects of Kollicoat IR and hydroxypropyl-beta-cyclodextrin on the dissolution rate of omeprazole from its microparticles and enteric-coated capsules.

    PubMed

    El-Badry, Mahmoud; Alanazi, Fars K; Mahrous, Gamal M; Alsarra, Ibrahim A

    2010-01-01

    Omeprazole microparticles were prepared by different drying techniques using Kollicoat IR nd hydroxypropyl-beta-cyclodextrin hydrophilic polymers. Physico-chemical properties were investigated using differential scanning calorimetry and powder X-ray diffractometry. Dissolution rate was determined and compared to the physical mixtures and the morphology was studied using a scanning electron microscope. Omeprazole transformed from the crystalline state to the amorphous state as confirmed by the disappearance of its melting peak and the characteristic of the crystalline peaks. Omeprazole dissolution rate was enhanced significantly from its spray- and freeze-dried microparticles as compared to the corresponding physical mixtures and drug alone (P < 0.05). F3 and F5 formula possessed superior release rate over other formulations. In acidic medium, the release of drug from enteric-coated capsules was not detectable, while it is completely released within 40 min after changing dissolution medium to phosphate buffer (pH 7.4). The transformation of OME from crystalline to amorphous state by using either Kollicoat IR or hydroxylpropyl-beta-cyclodextrin is considered a promising way to improvement of drug dissolution. PMID:19814584

  14. Coupled. beta. -cyclodextrin and reverse-phase high-performance liquid chromatography for assessing biphenyl hydroxylase activity in hepatic 9000g supernatant

    SciTech Connect

    Weaver, D.E.; van Lier, R.B.

    1986-05-01

    Coupled ..beta..-cyclodextrin bonded-phase and reverse-phase high performance liquid chromatography with fluorescence detection has been employed to detect the major hydroxylated metabolites of biphenyl following in vitro incubation with hepatic 9000g supernatant. The method requires only 0.3 mg of protein and its sensitivity was as low as 0.36 nmol metabolite formed/mg protein/h (0.32 pmol injected) for 2-, 3-, and 4-hydroxybiphenyl. Microsomes need not be purified and no organic extraction or derivatization was required. The method was employed successfully with samples from rats and mice treated with Aroclor, ..beta..-naphthoflavone,or phenobarbital; from monkeys dosed with Aroclor; and from untreated dogs.

  15. Experimental and Theoretical Investigations on the Supermolecular Structure of Isoliquiritigenin and 6-O-α-d-Maltosyl-β-cyclodextrin Inclusion Complex

    PubMed Central

    Li, Bin; Liu, Benguo; Li, Jiaqi; Xiao, Huizhi; Wang, Junyi; Liang, Guizhao

    2015-01-01

    Isoliquiritigenin (ILTG) possesses many pharmacological properties. However, its poor solubility and stability in water hinders its wide applications. The solubility of bioactive compounds can often be enhanced through preparation and delivery of various cyclodextrin (CD) inclusion complexes. The 6-O-α-d-maltosyl-β-CD (G2-β-CD), as one of the newest developments of CDs, has high aqueous solubility and low toxicity, especially stable inclusion characteristics with bioactive compounds. In this work, we for the first time construct and characterize the supermolecular structure of ILTG/G2-β-CD by scanning electron microscopy (SEM), ultraviolet-visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD). The solubility of ILTG in water at 25 °C rises from 0.003 to 0.717 mg/mL by the encapsulation with G2-β-CD. Our experimental observations on the presence of the ILTG/G2-β-CD inclusion complex are further supported by the ONIOM(our Own N-layer Integrated Orbital molecular Mechanics)-based QM/MM (Quantum Mechanics/Molecular Mechanics) calculations, typically substantiating these supermolecular characteristics, such as detailed structural assignments, preferred binding orientations, selectivity, solvent effects, interaction energies and forces of the ILTG/G2-β-CD inclusion complex. Our results have elucidated how ILTG interacts with G2-β-CD, demonstrating the primary host-guest interactions between ILTG and G2-β-CD, characterized by hydrogen bonds, hydrophobic interactions, electrostatic forces, and conformational effects, are favored for the formation of the ILTG/G2-β-CD inclusion. PMID:26247946

  16. Ternary inclusion complex formation and stabilization of limaprost, a prostaglandin E1 derivative, in the presence of α- and β-cyclodextrins in the solid state.

    PubMed

    Inoue, Yasuo; Iohara, Daisuke; Sekiya, Noboru; Yamamoto, Masanobu; Ishida, Hiroyuki; Sakiyama, Yoko; Hirayama, Fumitoshi; Arima, Hidetoshi; Uekama, Kaneto

    2016-07-25

    Limaprost/α-cyclodextrin (CD)/β-CD ternary inclusion complex was prepared by freeze-drying a solution containing all three components. Under humid conditions, limaprost was more stable in the ternary α-/β-CD inclusion complex than in the binary α- or β-CD complex. Specifically, during storage at 30°C/75% relative humidity (R.H.) for 4 weeks, about 19% of limaprost degraded into 17S,20-dimethyl-trans-Δ(2)-prostaglandin A1 (referred as 11-deoxy-Δ(10)) in the β-CD complex, 8.1% degraded in the α-CD complex, and only 2.2% degraded in the α-/β-CD complex. The mechanism of limaprost stabilization in the presence of both CDs was investigated by Raman and solid-state NMR spectroscopy and powder X-ray diffractometry. The fast degradation of limaprost to 11-deoxy-Δ(10) in the β-CD complex was due to the rapid crystallization of β-CD from the complex, liberating the free amorphous drug, which is susceptible to degradation. The dissociation and crystallization of β-CD from the inclusion complex were suppressed by freeze-drying limaprost in the presence of both α- and β-CDs. In addition, the interaction between limaprost and the two CDs was reinforced by inclusion of different moieties of limaprost: α-CD predominantly included the alkyl ω-chain, whereas β-CD included the five-membered ring. Thus, a stable ternary inclusion complex was formed that included limaprost, maintaining the amorphous state of the complex and dramatically stabilizing the drug under humid conditions. PMID:27286633

  17. Combination of β-cyclodextrin inclusion complex and self-microemulsifying drug delivery system for photostability and enhanced oral bioavailability of methotrexate: novel technique.

    PubMed

    Bourkaib, Nadia; Zhou, Jianping; Yao, Jing; Fang, Zhengjie; Mezghrani, Omar

    2013-06-01

    In the present study, we prepared an inclusion complex of methotrexate (MTX) with β-cyclodextrin (β-CD) in order to decrease its photosensitivity and enhance its aqueous solubility. Then we incorporated this inclusion complex in a self-microemulsifying drug delivery system (SMEDDS) overall to increase its oral bioavailability. The inclusion complex has been prepared by freeze drying method and characterized by differential scanning calorimetry (DSC), ultraviolet (UV), and infrared (IR) spectroscopy assays. The proper molecular ratio of MTX/β-CD was found to be of 1:7, and the water-solubility of MTX was increased in an average of 10-fold. The photostability studies showed that the MTX became stable on exposure to light. Construction of pseudoternary diagrams were investigated to prepare a MTX/β-CD inclusion complex loaded SMEDDS which was characterized by measuring the particle size and the zeta-potential. The optimum formulation of SMEDDS was a system consisting of ethyl oleate, tween 80, and propylene glycol with a mean droplet size of 39.42 nm. In vitro drug release in different pH media showed that the release profile of MTX from the MTX/β-CD loaded SMEDDS was influenced by the pH of the release medium and presented the characteristics of a sustained release profile. Finally, in-vivo studies showed an enhancement of the bioavailability of MTX from the MTX/β-CD loaded SMEDDS form of 1.57-fold. We concluded that the β-CD inclusion complex loaded SMEDDS improved the chemical and physiological properties of MTX and could be a promising means for the delivery of MTX and other unstable and lipophilic drugs by oral route. PMID:22998295

  18. Hydrogels composed of cyclodextrin inclusion complexes with PLGA-PEG-PLGA triblock copolymers as drug delivery systems.

    PubMed

    Khodaverdi, Elham; Mirzazadeh Tekie, Farnaz Sadat; Hadizadeh, Farzin; Esmaeel, Haydar; Mohajeri, Seyed Ahmad; Sajadi Tabassi, Sayyed A; Zohuri, Gholamhossein

    2014-02-01

    Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEGPLGA and α-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined. PMID:24234803

  19. Preliminary In Vitro Evaluation of Genistein Chemopreventive Capacity as a Result of Esterification and Cyclodextrin Encapsulation

    PubMed Central

    Danciu, Corina; Soica, Codruta; Dehelean, Cristina; Zupko, Istvan; Csanyi, Erzsebet; Pinzaru, Iulia

    2015-01-01

    The present study focuses on the synthesis and analysis of a genistein ester derivative with myristic acid followed by beta cyclodextrin encapsulation; physicochemical analysis using consecrated techniques such as FTIR, MS, DSC, and SEM revealed both a successful esterification and inclusion inside the cyclodextrin cavity. Cytotoxic effects were measured in vitro on three human cell lines: HeLa (cervix adenocarcinoma), A2780 (ovary carcinoma), and A431 (skin epidermoid carcinoma). The in vitro biological analysis exhibited rather poor antiproliferative results on all three tested cancer cell lines, behavior that may be due to the high stability of the complex within the in vitro environment. PMID:26161301

  20. Host-Guest Inclusion Complexation of α-Cyclodextrin and Triiodide Examined Using UV-Vis Spectrophotometry.

    PubMed

    Pursell, Janet L; Pursell, Christopher J

    2016-04-01

    The historically relevant host-guest complexation of α-cyclodextrin (α-CD) and triiodide (I3(-)) in aqueous solution was examined using a systematic UV-vis spectrophotometric approach. This particular system is experimentally challenging because of the coupled equilibria, namely, I2 + I(-) ⇌ I3(-) and α-CD + I3(-) ⇌ α-CD·I3(-). We therefore developed a unique experimental approach that allowed us to determine the concentration of all iodine species. This enabled us to unequivocally demonstrate that the large increase in the UV absorbance with added α-cyclodextrin is due to an increase in the overall triiodide concentration as α-CD essentially converts iodine to triiodide according to the coupled equilibria. Herein we report (a) the complexation stoichiometry is 1:1 (i.e., the host-guest complex is α-CD·I3(-)), (b) the binding constant is KH-G = (1.35 ± 0.05) × 10(5) M(-1) at room temperature, and PMID:26997285

  1. Simultaneous elution of polycyclic aromatic hydrocarbons and heavy metals from contaminated soil by two amino acids derived from beta-cyclodextrins.

    PubMed

    Yang, Chengjian; Zeng, Qingru; Wang, Yunzhong; Liao, Bohan; Sun, Jian; Shi, Hui; Chen, Xingdou

    2010-01-01

    Two highly water-soluble amino acids, which derived from beta-CDs, i.e., glutamic acid-beta-cyclodextrin (GluCD) and ethylene-diamine-beta-cyclodextrin (EDCD), were synthesized and were examined for their effect on solubilization of anthracene (ANT), complexation of cadmium (Cd2+), and elution removal of ANT and Cd2+ in soil. The results showed that GluCD and EDCD were powerful complexant for ANT and Cd2+. In the presence of 10 g/L GluCD and EDCD, the solubilization of ANT increased by 47.04 and 23.85 times compared to the control, respectively. GluCD resulted in approximately 90% complexation of Cd2+ while 70% complexation was observed for EDCD. Simultaneously, GluCD and EDCD could greatly enhance the elution removal of ANT and Cd2+ from soil. GluCD resulted in the highest elution efficiency of ANT and Cd2+. With the addition of 10 g/L GluCD, 53.5% of ANT and 85.6% of Cd2+ were eluted, respectively. The ANT had a negligible effect on the Cd2+ removal due to different complexing sites of ANT and Cd2+, while Cd2+ enhanced the ANT removal under the addition of GluCD because Cd2+ neutralized the -COOH group of GluCD. Adversely, the removal of ANT was decreased with Cd2+ under the addition of EDCD, this was due to the fact that Cd2+ enhanced the polarity of EDCD molecule and inhibited the complexation between ANT and EDCD. The study suggested that GluCD could be preferred and be successfully applied to remediation of heavy metals or organic compounds in contaminated soil. PMID:21462709

  2. A DFT study of infrared spectra and Monte Carlo predictions of the solvation shell of Praziquantel and β-cyclodextrin inclusion complex in liquid water.

    PubMed

    de Oliveira, C X; Ferreira, N S; Mota, G V S

    2016-01-15

    In this paper, we report a theoretical study of the inclusion complexes of Praziquantel (PZQ) and β-cyclodextrin (β-CD) in liquid water. The starting geometry has been carried out by molecular mechanics simulations, and afterwards optimized in B3LYP level with a 6-311G(d) basis set. Monte Carlo simulations have been used to calculate the solvation shell of the PZQ/β-CD inclusion complexes. Moreover, the vibrational frequencies and the infrared intensities for the PZQ/β-CD complex were computed using the B3LYP method. It is demonstrated that this combined model can yield well-converged thermodynamic data even for a modest number of sample configurations, which makes the methodology particularly adequate for understanding the solute-solvent interaction used for generating the liquid structures of one solute surrounded by solvent molecules. The complex solvation shell showed an increase of the water molecule level in relation to the isolated PZQ molecule because of the hydrophilic effect of the CD molecule. The infrared spectra showed that the contribution that originated in the PZQ molecule was not predominant in the upper-wave number region in the drug/β-CD. The movement that purely originated in the PZQ molecule was localized in the absorption band, ranging from 1328 to 1688cm(-1). PMID:26296254

  3. A DFT study of infrared spectra and Monte Carlo predictions of the solvation shell of Praziquantel and β-cyclodextrin inclusion complex in liquid water

    NASA Astrophysics Data System (ADS)

    de Oliveira, C. X.; Ferreira, N. S.; Mota, G. V. S.

    2016-01-01

    In this paper, we report a theoretical study of the inclusion complexes of Praziquantel (PZQ) and β-cyclodextrin (β-CD) in liquid water. The starting geometry has been carried out by molecular mechanics simulations, and afterwards optimized in B3LYP level with a 6-311G(d) basis set. Monte Carlo simulations have been used to calculate the solvation shell of the PZQ/β-CD inclusion complexes. Moreover, the vibrational frequencies and the infrared intensities for the PZQ/β-CD complex were computed using the B3LYP method. It is demonstrated that this combined model can yield well-converged thermodynamic data even for a modest number of sample configurations, which makes the methodology particularly adequate for understanding the solute-solvent interaction used for generating the liquid structures of one solute surrounded by solvent molecules. The complex solvation shell showed an increase of the water molecule level in relation to the isolated PZQ molecule because of the hydrophilic effect of the CD molecule. The infrared spectra showed that the contribution that originated in the PZQ molecule was not predominant in the upper-wave number region in the drug/β-CD. The movement that purely originated in the PZQ molecule was localized in the absorption band, ranging from 1328 to 1688 cm- 1.

  4. Mathematical modelling of the transport of hydroxypropyl-β-cyclodextrin inclusion complexes of ranitidine hydrochloride and furosemide loaded chitosan nanoparticles across a Caco-2 cell monolayer.

    PubMed

    Sadighi, Armin; Ostad, S N; Rezayat, S M; Foroutan, M; Faramarzi, M A; Dorkoosh, F A

    2012-01-17

    Chitosan nanoparticles (CS-NPs) have been used to enhance the permeability of furosemide and ranitidine hydrochloride (ranitidine HCl) which were selected as candidates for two different biopharmaceutical drug classes having low permeability across Caco-2 cell monolayers. Drugs loaded CS-NPs were prepared by ionic gelation of CS and pentasodium tripolyphosphate (TPP) which added to the drugs inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-βCD). The stability constants for furosemide/HP-βCD and ranitidine HCl/HP-βCD were calculated as 335 M(-1) and 410 M(-1), whereas the association efficiencies (AE%) of the drugs/HP-βCD inclusion complexes with CS-NPs were determined to be 23.0 and 19.5%, respectively. Zetasizer and scanning electron microscopy (SEM) were used to characterise drugs/HP-βCD-NPs size and morphology. Transport of both nano and non-nano formulations of drugs/HP-βCD complexes across a Caco-2 cell monolayer was assessed and fitted to mathematical models. Furosemide/HP-βCD-NPs demonstrated transport kinetics best suited for the Higuchi model, whereas other drug formulations demonstrated power law transportation behaviour. Permeability experiments revealed that furosemide/HP-βCD and ranitidine HCl/HP-βCD nano formulations greatly induce the opening of tight junctions and enhance drug transition through Caco-2 monolayers. PMID:22101294

  5. Characterization of Albendazole-Randomly Methylated-β-Cyclodextrin Inclusion Complex and In Vivo Evaluation of Its Antihelmitic Activity in a Murine Model of Trichinellosis

    PubMed Central

    García, Agustina; Leonardi, Darío; Vasconi, María D.; Hinrichsen, Lucila I.; Lamas, María C.

    2014-01-01

    Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its broad spectrum activity, good tolerance and low cost. However, the drug has the disadvantage of poor bioavailability due to its very low solubility in water; as a consequence, a very active area of research focuses on the development of new pharmaceutical formulations to increase its solubility, dissolution rate, and bioavailability. The primary objective of this study was to prepare randomly methylated β-cyclodextrins inclusion complexes to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. This formulation therapeutic efficacy was contrasted with that of the pure drug by treating Trichinella spiralis infected mice during the intestinal phase of the parasite cycle, on days five and six post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral stage on day 30 post-infection, when compared with the untreated control. Thus, it could be demonstrated that the inclusion complexes improve the in vivo therapeutic activity of albendazole. PMID:25406084

  6. Inclusion compounds between α-, β- and γ-cyclodextrins: iron II lactate: a theoretical and experimental study using diffusion coefficients and molecular mechanics

    NASA Astrophysics Data System (ADS)

    Leite, Rosiley A.; Lino, Antonio C. S.; Takahata, Yuji

    2003-01-01

    The inclusion compounds between iron II lactate and three different cyclodextrins (CDs) were studied by means of experimental and theoretical data. The importance of iron II in the human metabolism effort the necessity of a minimum concentration to the human life. Malnutrition is one great problem in social politics of many countries on the world. The possibility to the development of novel medicines with the iron II species stable look for an increase on the efficiency for this kind of aid. Kinetics measurements confirm the possibility to stop the oxidation reaction. It was the first indication of efficient molecular encapsulation. Diffusion coefficient measurements were carried out by Taylor-Aris diffusion technique. The decrease of diffusion coefficients measured for iron II lactate when alone and forming the inclusion complexes was obtained for all hosts molecules used. Molecular Mechanics calculations were performed to elucidate the perfect arrange of iron II lactate inside CDs cavity. No great differences were obtained to the binding energy for the different hosts. Using the software HyperChem6.03v MM+, AMBER94 and OPLS Forced Fields for iron atom in two chemical environments (a) vacuum and (b) with addition of 250 water molecules (MM+). The solvent treatment was decisive to the order of stability. This order was β-CD>γ-CD>α-CD, the same order of solubility in water. The results contained in this work confirm the possibility to protect iron II lactate against oxidation.

  7. Synthesis, Characterization, In Vitro Evaluation, and Preclinical Profiling of beta-Cyclodextrin Polyrotaxane Families for Use As Potential Niemann-Pick Type C Therapeutics

    NASA Astrophysics Data System (ADS)

    Collins, Christopher J.

    Niemann-Pick Disease Type C (NPC) is a rare, autosomal recessive genetic disorder featuring a loss of proteins responsible for unesterified cholesterol (UC) trafficking through the late endosomes/lysosomes (LE/LY) of every cell of the body. Disruption of this pathway leads to abnormal accumulation and storage of UC and other lipids. A broad range of visceral and neurological symptoms result from this accumulation exhibiting a variable age of onset and a disease progression that is ultimately fatal. The disease has an incidence of approximately 1 in 120,000 live births and has no known effective treatment. beta-Cyclodextrin (beta-CD) are natural small molecules macrocycles composed of glucose units with a hydrophobic inner cavity and hydrophilic outer rims. beta-CD derivatives have recently been shown to be effective therapeutics for NPC in cellular and animal models. In the mouse model of the disease, beta-CD therapy increases overall lifetime by as much as 50% and slows the progression of neurodegeneration. The progress has led to the initiation of a National Institutes of Health phase I clinical trial. A main drawback of beta-CD administration is the poor pharmacokinetic profile characterized by rapid renal clearance of the drug through the urine. Libraries of beta-CD derivative carrying high molecular weight polyrotaxane (PR) systems have been designed to prevent glomerular filtration of the injected beta-CD dose. An initial family of unmodified beta-CD PRs was synthesized, characterized, and their therapeutic efficacy was tested in NPC fibroblasts. This was followed by screening of PRs consisting of mixed beta-CD derivative threading featuring charged sulfobutylether beta-CD. Finally, we sought to define PR structure-property effects on in vivo pharmacokinetics, biodistribution, toxicity, immunogenicity, and protein hard corona composition. This was accomplished using a family of gadolinium carrying PRs composed of triblock Pluronic co-polymers of varying

  8. Physicochemical characterization and dissolution properties of nimesulide-cyclodextrin binary systems.

    PubMed

    Nalluri, Buchi N; Chowdary, K P R; Murthy, K V R; Hayman, A R; Becket, G

    2003-01-01

    The objective of this work is physicochemical characterization of nimesulide-cyclodextrin binary systems both in solution and solid state and to improve the dissolution properties of nimesulide (N) via complexation with alpha-, beta, and gamma-cyclodextrins (CDs). Detection of inclusion complexation was done in solution by means of phase solubility analysis, mass spectrometry, and 1H nuclear magnetic resonance (1H-NMR) spectroscopic studies, and in solid state using differential scanning calorimetry (DSC), powder x-ray diffractometry (X-RD), scanning electron microscopy (SEM), and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H-NMR studies in solution revealed 1:1 M complexation of N with all CDs. A true inclusion of N with beta-CD at 1:2 M in solid state was confirmed by DSC, powder X-RD and SEM studies. Dissolution properties of N-CD binary systems were superior when compared to pure N. PMID:12916912

  9. Spray-dried voriconazole-cyclodextrin complexes: solubility, dissolution rate and chemical stability.

    PubMed

    Miletic, Tijana; Kyriakos, Kachrimanis; Graovac, Adrijana; Ibric, Svetlana

    2013-10-15

    The present work investigates the effect of complexation with hydroxypropyl-beta-cyclodextrin (HPBCD) and 2-O-methyl-beta-cyclodextrin (2-O-MBCD), on voriconazole solubility, dissolution rate and chemical stability. Drug-cyclodextrin complexes were prepared as aqueous solutions, which were spray-dried, and their properties were compared to wet ground samples and physical mixtures. DSC analysis revealed absence of crystalline voriconazole from spray-dried complexes. FTIR spectroscopy indicated changes in the H-bonding network of the hydroxyl groups of cyclodextrin following drug inclusion. Dissolution rate of voriconazole was significantly higher from spray-dried complexes with either cyclodextrin in comparison with free drug, physical mixtures, or wet ground mixtures. However, two degradation impurities were found in aged samples, with slightly higher impurity level with HPBCD. Performed solubility studies suggested that 2-O-MBCD is more efficient solubilizer. Molecular docking simulations showed a difference in the 1:1 binding affinities and sites, with HPBCD surprisingly forming complexes of much lower energy, thus suggesting a multiple rather than a 1:1 complexation. PMID:23987325

  10. Inclusion of an Anthracene-based Fluorophore within Molecular Containers: A Comparative Study of the Cucurbituril and Cyclodextrin Host Families.

    PubMed

    Ganguly, Aniruddha; Ghosh, Soumen; Guchhait, Nikhil

    2016-05-19

    In this paper, the binding interaction of a promising chloride channel blocker, 9-methyl anthroate (9-MA), with two different classes of molecular containers, β-cyclodextrins (β-CD and methyl-β-CD) and cucurbit[7]uril, having comparable cavity dimensions, has been thoroughly demonstrated via inspection of the modulation of the excited-state properties of the emissive molecule. Spectral data suggest that CB7 encapsulates the probe more efficiently in a 1:2 fashion, whereas the efficacies of β-CDs are relatively less and the corresponding stoichiometry is 1:1. Interestingly, despite being thermodynamically much more favorable than the probe-β-CD complexation equilibria, the fraction of probe-CB7 complex formed is appreciably smaller with respect to that of probe-β-CD complexes. This apparent inconsistency has been addressed via the proposition that since the formation of a 1:2 complex is entropically disadvantageous, it is anticipated that the activation barrier of the corresponding reaction is reasonably high, and thus only a small fraction of the reactants are able to surpass the energy barrier to form the products. This proposition has been thoroughly corroborated by fluorescence lifetime measurements at different temperatures. PMID:27119387

  11. Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes.

    PubMed

    Ezawa, Toshinari; Inoue, Yutaka; Tunvichien, Sujimon; Suzuki, Rina; Kanamoto, Ikuo

    2016-01-01

    Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and β-cyclodextrin (βCD) (molar ratio of PP/βCD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and βCD were observed. Based on Job's plot, the PP/βCD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH2), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure βCD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and βCD cavity was detected by (1)H-(1)H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy. PMID:26998357

  12. Changes in the Physicochemical Properties of Piperine/β-Cyclodextrin due to the Formation of Inclusion Complexes

    PubMed Central

    Ezawa, Toshinari; Inoue, Yutaka; Tunvichien, Sujimon; Suzuki, Rina; Kanamoto, Ikuo

    2016-01-01

    Piperine (PP) is a pungent component in black pepper that possesses useful biological activities; however it is practically insoluble in water. The aim of the current study was to prepare a coground mixture (GM) of PP and β-cyclodextrin (βCD) (molar ratio of PP/βCD = 1/1) and subsequently evaluate the solubility of PP and physicochemical properties of the GM. DSC thermal behavior of the GM showed the absence of melting peak of piperine. PXRD profile of the GM exhibited halo pattern and no characteristic peaks due to PP and βCD were observed. Based on Job's plot, the PP/βCD complex in solution had a stoichiometric ratio of 1/1. Raman spectrum of the GM revealed scattering peaks assigned for the benzene ring (C=C), the methylene groups (CH2), and ether groups (C-O-C) of PP that were broaden and shifted to lower frequencies. SEM micrographs showed that particles in the GM were agglomerated and had rough surface, unlike pure PP and pure βCD particles. At 15 min of dissolution testing, the amount dissolved of PP in the GM was dramatically increased (about 16 times) compared to that of pure PP. Moreover the interaction between PP and βCD cavity was detected by 1H-1H NMR nuclear Overhauser effect spectroscopy NMR spectroscopy. PMID:26998357

  13. Effect of inclusion of hydroxycinnamic and chlorogenic acids from green coffee bean in β-cyclodextrin on their interactions with whey, egg white and soy protein isolates.

    PubMed

    Budryn, Grażyna; Pałecz, Bartłomiej; Rachwał-Rosiak, Danuta; Oracz, Joanna; Zaczyńska, Donata; Belica, Sylwia; Navarro-González, Inmaculada; Meseguer, Josefina María Vegara; Pérez-Sánchez, Horacio

    2015-02-01

    The aim of the study was to characterise the interactions of hydroxycinnamic and chlorogenic acids (CHAs) from green coffee, with isolates of proteins from egg white (EWP), whey (WPC) and soy (SPI), depending on pH and temperature. The binding degree was determined by liquid chromatography coupled to a diode array detector and an ultrahigh resolution hybrid quadruple-time-of-flight mass spectrometer with ESI source (LC-QTOF-MS/MS). As a result of binding, the concentration of CHAs in proteins ranged from 9.44-12.2, 11.8-13.1 and 12.1-14.4g/100g for SPI, WPC and EWP, respectively. Thermodynamic parameters of protein-ligand interactions were determined by isothermal titration calorimetry (ITC) and energetics of interactions at the atomic level by molecular modelling. The amount of CHAs released during proteolytic digestion was in the range 0.33-2.67g/100g. Inclusion of CHAs with β-cyclodextrin strongly limited these interactions to a level of 0.03-0.06g/100g. PMID:25172711

  14. [Synthesis and bioactivity of the folate receptor targeted gamma-cyclodextrin-folate inclusion-coated CdSe/ZnS quantum dots].

    PubMed

    Zhao, Mei-Xia; Li, Yang; Wang, Chao-Jie

    2013-04-01

    The gamma-cyclodextrin-folate (gamma-CD/FA) inclusion-coated CdSe/ZnS quantum dots (QDs) with folate-receptor (FR) targeted were synthesized by simple and convenient sonochemical method. The products were studied using Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), utraviolet-visible spectrometry (UV-vis), fluorescence spectrum and transmission electron micrographs (TEM). The results showed that the gamma-CD/FA-coated CdSe/ZnS QDs not only have good monodispersity and smaller size, but also have good optical performance, such as higher quantum yield (QY) and a long fluorescence lifetime. The cytotoxicity experiments showed that the gamma-CD/FA-coated CdSe/ZnS QDs have lower cytotoxicity and could more effectively enter cancer cells with FR over-expression. The QDs with 4-5 nm in diameter were relatively easy to enter the cell and to be removed through kidneys, so it is more suitable for biomedical applications for bioprobes and bioimaging. PMID:23833947

  15. Self-assembled supramolecular hydrogel based on PCL-PEG-PCL triblock copolymer and γ-cyclodextrin inclusion complex for sustained delivery of dexamethasone.

    PubMed

    Khodaverdi, Elham; Gharechahi, Marzieh; Alibolandi, Mona; Tekie, Farnaz Sadat Mirzazadeh; Khashyarmanesh, Bibi Zahra; Hadizadeh, Farzin

    2016-01-01

    In this study, thermosensitive, water-soluble, and biodegradable triblock copolymer PCL600-PEG6000-PCL600 was used to form supramolecular hydrogel (SMGel) by inclusion complexation with γ-cyclodextrin (γ-CD). The prepared SMGel was investigated as a carrier for sustained release of dexamethasone. The triblock copolymer PCL-PEG-PCL [where PCL = polycaprolactone, PEG = poly(ethylene glycol)] was synthesized by the ring-opening polymerization method using microwave irradiation. The polymerization reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). SMGel was prepared in aqueous solution by blending an aqueous γ-CD solution with aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. The sol-to-gel transition time was measured at various concentrations of copolymer and γ-CD. As-prepared SMGel was used to prepare a sustained, controllable drug delivery system of dexamethasone sodium phosphate. The SMGel was also characterized in terms of rheological, morphological, and structural properties. Results obtained from proton nuclear magnetic resonance ( (1)H-NMR) and GPC demonstrated that microwave irradiation is a simple and reliable method for synthesis of PEG-PCL copolymer. The SMGel with excellent syringability was prepared by mixing of 20% wt γ-CD and 10% wt of copolymer within 4 s. The SMGel containing 10% wt copolymer, 20% wt γ-CD, and 0.5% or 0.1% wt dexamethasone released approximately 100% and 45% of drug over up to 23 days, respectively. It could be concluded that SMGel based on self-assembly of inclusion complexes between PCL-PEG-PCL copolymer and γ-CD could be used as a basis for injectable drug delivery systems that provide sustained and controlled release of macromolecular drugs such as dexamethasone. PMID:27051627

  16. Self-assembled supramolecular hydrogel based on PCL-PEG-PCL triblock copolymer and γ-cyclodextrin inclusion complex for sustained delivery of dexamethasone

    PubMed Central

    Khodaverdi, Elham; Gharechahi, Marzieh; Alibolandi, Mona; Tekie, Farnaz Sadat Mirzazadeh; Khashyarmanesh, Bibi Zahra; Hadizadeh, Farzin

    2016-01-01

    In this study, thermosensitive, water-soluble, and biodegradable triblock copolymer PCL600-PEG6000-PCL600 was used to form supramolecular hydrogel (SMGel) by inclusion complexation with γ-cyclodextrin (γ-CD). The prepared SMGel was investigated as a carrier for sustained release of dexamethasone. The triblock copolymer PCL-PEG-PCL [where PCL = polycaprolactone, PEG = poly(ethylene glycol)] was synthesized by the ring-opening polymerization method using microwave irradiation. The polymerization reaction and the copolymer structures were evaluated by nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). SMGel was prepared in aqueous solution by blending an aqueous γ-CD solution with aqueous solution of PCL-PEG-PCL triblock copolymer at room temperature. The sol-to-gel transition time was measured at various concentrations of copolymer and γ-CD. As-prepared SMGel was used to prepare a sustained, controllable drug delivery system of dexamethasone sodium phosphate. The SMGel was also characterized in terms of rheological, morphological, and structural properties. Results obtained from proton nuclear magnetic resonance ( 1H-NMR) and GPC demonstrated that microwave irradiation is a simple and reliable method for synthesis of PEG-PCL copolymer. The SMGel with excellent syringability was prepared by mixing of 20% wt γ-CD and 10% wt of copolymer within 4 s. The SMGel containing 10% wt copolymer, 20% wt γ-CD, and 0.5% or 0.1% wt dexamethasone released approximately 100% and 45% of drug over up to 23 days, respectively. It could be concluded that SMGel based on self-assembly of inclusion complexes between PCL-PEG-PCL copolymer and γ-CD could be used as a basis for injectable drug delivery systems that provide sustained and controlled release of macromolecular drugs such as dexamethasone. PMID:27051627

  17. Optimisation of spray-drying process variables for dry powder inhalation (DPI) formulations of corticosteroid/cyclodextrin inclusion complexes.

    PubMed

    Cabral-Marques, Helena; Almeida, Rita

    2009-09-01

    This study aims to develop and characterise a beclomethasone diproprionate:gamma-cyclodextrin (BDP:gamma-CYD) complex and to optimise the variables on the spray-drying process, in order to obtain a powder with the most suitable characteristics for lung delivery. The spray-dried powder--in a mass ratio of 2:5 (BDP:gamma-CYD)--was physically mixed with three carriers of different particle sizes and in different ratios. Particle-size distribution, shape and morphology, moisture content, and uniformity in BDP content of formulations were studied. In vitro aerolisation behaviour of the formulations was evaluated using the Rotahaler, and the performance was characterised based on the uniformity of emitted dose and aerodynamic particle-size distribution (respirable fraction (RF), as a percentage of nominal dose (RFN) and emitted dose (RFE)). The most suitable conditions for the preparation of BDP:gamma-CYD complexes were obtained with the solution flow of 5 ml/min, T(in) of 70 degrees C and T(out) of 50 degrees C. Statistically significant differences in the aerodynamic performances were obtained for formulations containing BDP:gamma-CYD complexes prepared using different solution flows and different T(in) (p<0.05). RFN and RFE vary in direct proportion with T(in), while an inverse relationship was observed for the solution flow. A direct correlation between the RFE and the T(out) was identified. Performance of the formulations was compared with an established commercial product (Beclotaide Rotacaps 100 microg) with improved performance of RF: formulations with respitose carrier attained RFN and RFE twofold greater, and formulations based on 63-90 microm fraction lactose and trehalose achieved a threefold improvement; also, all formulations showed that the percentage of dose of BDP deposited in the "oropharynx" compartment was reduced to half. PMID:19446024

  18. Study of inclusion complex between 2,6-dinitrobenzoic acid and β-cyclodextrin by 1H NMR, 2D 1H NMR (ROESY), FT-IR, XRD, SEM and photophysical methods.

    PubMed

    Srinivasan, Krishnan; Stalin, Thambusamy

    2014-09-15

    The formation of host-guest inclusion complex of 2,6-dinitrobenzoic acid (2,6-DNB) with nano-hydrophobic cavity of β-cyclodextrin (β-CD) in solution phase has been studied by UV-visible spectroscopy and electrochemical analysis (cyclic voltammetry, CV). The effect of acid-base concentrations of 2,6-DNB has been studied in presence and absence of β-CD to determination for the ground state acidity constant (pKa). The binding constant of inclusion complex at 303 K was calculated using Benesi-Hildebrand plot and thermodynamic parameter (ΔG) was also calculated. The solid inclusion complex formation between β-CD and 2,6-DNB was confirmed by 1H NMR, 2D 1H NMR (ROESY), FT-IR, XRD and SEM analysis. A schematic representation of this inclusion process was proposed by molecular docking studies using patch dock server. PMID:24769381

  19. Study of inclusion complex between 2,6-dinitrobenzoic acid and β-cyclodextrin by 1H NMR, 2D 1H NMR (ROESY), FT-IR, XRD, SEM and photophysical methods

    NASA Astrophysics Data System (ADS)

    Srinivasan, Krishnan; Stalin, Thambusamy

    2014-09-01

    The formation of host-guest inclusion complex of 2,6-dinitrobenzoic acid (2,6-DNB) with nano-hydrophobic cavity of β-cyclodextrin (β-CD) in solution phase has been studied by UV-visible spectroscopy and electrochemical analysis (cyclic voltammetry, CV). The effect of acid-base concentrations of 2,6-DNB has been studied in presence and absence of β-CD to determination for the ground state acidity constant (pKa). The binding constant of inclusion complex at 303 K was calculated using Benesi-Hildebrand plot and thermodynamic parameter (ΔG) was also calculated. The solid inclusion complex formation between β-CD and 2,6-DNB was confirmed by 1H NMR, 2D 1H NMR (ROESY), FT-IR, XRD and SEM analysis. A schematic representation of this inclusion process was proposed by molecular docking studies using patch dock server.

  20. Preparation and characterization of host-guest system between inosine and β-cyclodextrin through inclusion mode

    NASA Astrophysics Data System (ADS)

    Prabu, Samikannu; Sivakumar, Krishnamurty; Swaminathan, Meenakshisundaram; Rajamohan, Rajaram

    2015-08-01

    Inosine is a nucleoside that is formed when hypoxanthine is attached to a ribose ring (also known as a ribofuranose) via a β-N9-glycosidic bond. Inosine is commonly found in tRNAs. Inosine (INS) has been used widely as an antiviral drug. The inclusion complex of INS with β-CDx in solution phase is studied by ground and excited state with UV-visible and fluorescence spectroscopy, respectively. A binding constant and stoichiometric ratio between INS and β-CDx are calculated by BH equation. The lifetime and relative amplitude of INS is increases with increasing the concentrations of β-CDx, confirms the formation of inclusion complex in liquid state. The solid complexes are prepared by kneading method (KM) and co-precipitation method (CP). The solid complex is characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (XRD) and differential scanning colorimetry (DSC). CP method gives the solid product with good yield than that of physical mixture and KM method. The structure of complex is proposed based on the study of Patch - Dock server.

  1. Characterization of a new TiF(4) and β-cyclodextrin inclusion complex and its in vitro evaluation on inhibiting enamel demineralization.

    PubMed

    Nassur, Camila; Alexandria, Adílis Kalina; Pomarico, Luciana; de Sousa, Valeria Pereira; Cabral, Lúcio Mendes; Maia, Lucianne Cople

    2013-03-01

    Titanium tetrafluoride (TiF(4)) is an effective but instable caries preventive agent. As the stability problems could be minimized through the use of drug carriers this study aimed to prepare and characterize a new TiF(4) nanoinclusion complex and to evaluate its potential in inhibiting enamel demineralization under pH cycling conditions. The TiF(4) nanosystems were prepared using β-cyclodextrin (βCD) and sodium montmorillonite (MMTNa). Bovine enamel blocks (n=48) with known surface microhardness (SMH), were randomly assigned to 4 groups (n=12) and submitted to one of the following treatments: distilled deionized water (as negative control) and solutions containing 1% βCD, 1% TiF(4) and TiF(4):βCD. The solutions were blinded applied once on the blocks with a microbrush(®) on the surface for 1min before pH-cycling. After that, samples were reavaluated by SMH, %SMH loss, cross-sectional microhardness (CSMH), scanning electron microscope (SEM) and energy dispersive spectrometry (EDX). The inclusion complex of TiF(4):βCD offered better protection against demineralization in the subsurface. The SEM analysis showed that TiF(4) and TiF(4):βCD samples presented the most intact enamel than the control. The EDX analysis identified titanium in TiF(4) and TiF(4):βCD groups. TiF(4):βCD has higher potential on inhibiting demineralization in the inner enamel. TiF(4):βCD is a new alternative to TiF(4) stabilization in order to reduce enamel subsurface demineralization. PMID:23246339

  2. Beta-amyloid protein-containing inclusions in skeletal muscle of apolipoprotein-E-deficient mice.

    PubMed Central

    Robertson, T. A.; Dutton, N. S.; Martins, R. N.; Roses, A. D.; Kakulas, B. A.; Papadimitriou, J. M.

    1997-01-01

    The tibialis anterior muscle and soleus muscle of apolipoprotein-E-deficient mice were examined by light and electron microscopy. By light microscopy, sarcoplasmic inclusions were seen in tibialis anterior muscle and 40% of type 2 myofibers were affected in all animals over 8 months of age. These inclusions reacted for nonspecific esterase, cytochrome oxidase, and myoadenylate deaminase and were also periodic acid Schiff positive and stained basophilic with hematoxylin. Moreover, they reacted immunocytochemically with an antibody specific to fragment 17 to 24 of the published sequence of Alzheimer's cerebrovascular amyloid peptide. Immunoreactivity was lost when the antibody was adsorbed with the appropriate synthetic peptide. Ultrastructurally, the inclusions consisted of tubular arrays and were similar to those observed in human muscle in several pathological conditions. In type 1 myofibers of both tibialis anterior and soleus muscle, however, mitochondrial abnormalities including an increase in their number and size were detected, but tubular aggregates were not seen. These large mitochondria possessed an electron-dense inner chamber with an increased number of tightly packed cristae. The results obtained suggest that in these mice there is a disturbed lipid metabolism in skeletal muscle fibers that manifests itself with an accumulation of phospholipid in the form of sarcoplasmic reticulum tubules in the type 2 fibers and enlarged mitochondria with tightly packed cristae in the type 1 fibers. In addition, beta-amyloid protein was closely associated with the accumulated tubules and vesicles of sarcoplasmic reticulum and may represent dysregulation of amyloid precursor protein metabolism. Images Figure 1 Figure 2 Figure 3 PMID:9033257

  3. Inclusion.

    ERIC Educational Resources Information Center

    Nathanson, Jeanne H., Ed.

    1992-01-01

    This theme journal issue focuses on current activities of the Office of Special Education and Rehabilitative Services which stress inclusion of students with disabilities in the mainstream. It begins with a message from the Assistant Secretary, Robert R. Davila which examines the full meaning of an "inclusive" education. Next, Barbara Buswell and…

  4. Methyl-{beta}-cyclodextrin enhances the susceptibility of human breast cancer cells to carboplatin and 5-fluorouracil: Involvement of Akt, NF-{kappa}B and Bcl-2

    SciTech Connect

    Upadhyay, Ankur Kumar; Singh, Sandeep; Chhipa, Rishi Raj; Vijayakumar, Maleppillil Vavachan; Ajay, Amrendra Kumar; Bhat, Manoj Kumar . E-mail: manojkbhat@nccs.res.in

    2006-10-15

    The response rates of extensively used chemotherapeutic drugs, carboplatin (Carb) or 5-fluorouracil (5-FU) are relatively disappointing because of considerable side effects associated with their high-dose regimen. In the present study, we determined whether treatment with a cholesterol depleting agent, methyl-{beta}-cyclodextrin (MCD), enhances the weak efficacy of low doses of Carb or 5-FU in human breast cancer cells. Data demonstrate that pretreatment with MCD significantly potentiates the cytotoxic activity of Carb and 5-FU in both MCF-7 and MDA-MB-231. Furthermore, we explored the molecular basis of enhanced cytotoxicity, and our data revealed that low-dose treatment with these drugs in MCD pretreated cells exhibited significantly decreased Akt phosphorylation, NF-{kappa}B activity and down-regulation in expression of anti-apoptotic protein Bcl-2. In addition, MCD pretreated cells demonstrated an increased intracellular drug accumulation as compared to cells treated with drugs alone. Taken together, our data provide the basis for potential therapeutic application of MCD in combination with other conventional cytotoxic drugs to facilitate reduction of drug dosage that offers a better chemotherapeutic approach with low toxicity.

  5. Physicochemical characterization and dissolution properties of meloxicam-cyclodextrin binary systems.

    PubMed

    Naidu, N Buchi; Chowdary, K P R; Murthy, K V R; Satyanarayana, V; Hayman, A R; Becket, G

    2004-04-01

    The objective of the work is physicochemical characterization of meloxicam (ME)-cyclodextrin (CD) binary systems both in solution and solid states and to improve the dissolution properties of meloxicam via complexation with alpha-, beta- and gamma-cyclodextrins. Detection of inclusion complexation was done in solution state by means of phase solubility analysis, mass spectrometry and 1H nuclear magnetic resonance (NMR) studies, and in solid state using differential scanning calorimetry (DSC), powder X-ray diffractometry, and in vitro dissolution studies. Phase solubility, mass spectrometry and 1H NMR studies in solution state revealed 1:1M complexation of meloxicam with all CDs. A true inclusion of ME with gamma-CD at 1:1 and 1:2M in solid state was confirmed by DSC, powder XRD and scanning electron microscopy (SEM) studies. Dissolution properties of ME-CDs binary systems were superior when compared to pure ME. PMID:15030882

  6. Spectrophotometric study of the inclusion complex between β-cyclodextrin and dibenzoyl peroxide and its analytical application

    NASA Astrophysics Data System (ADS)

    Xie, Hui; Wang, Huai You; Ma, Li Ying; Xiao, Yan; Han, Juan

    2005-11-01

    The noncovalent interaction of dibenzoyl peroxide and β-cyclodextin (β-CD) has been studied by spectrophotometry. The mechanism of the inclusion was studied. The results showed that β-CD reacts with dibenzoyl peroxide to form a 2:1 host-guest complex with an apparent formation constant of 2.5 × 10 4 mol -2 L 2. The β-CD reacts with benzoic acid to form a 1:1 host-guest complex with an apparent formation constant of 6.9 × 10 2 mol -1 L after the dibenzoyl peroxide was reduced by hydroxyl ammonium. Based on the enhancement of the absorbance of dibenzoyl peroxide produced through complex formation, a spectrophotometric method for determination of dibenzoyl peroxide in bulk aqueous solution in the presence of β-CD was developed. A linear relationship between the absorbance and dibenzoyl peroxide concentration was obtained in the range of 0.300-50.0 μg mL -1. Linear regression equation of the calibration graph C = 0.02926 + 53.25 A, with a correlation coefficient of 0.9984 and a relative standard deviation (R.S.D.) of 3.4%. The detection limit was 0.200 μg mL -1, and the recovery was from 98.00 to 105.0%. The proposed method was used to determine the dibenzoyl peroxide in the flour with satisfactory results. The principal advantage of the proposed method is its excellent selectivity based on molecule recognition of β-CD.

  7. Study of the effects of cyclodextrins on the fluorescence detection of zearalenone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Successful applications of inclusion complexes to improve isolation and detection of small molecules have made cyclodextrins increasingly popular components in methods of detection. Studies of the effects of cyclodextrins on aflatoxins have advanced mycotoxin detection research. Recently, a capill...

  8. Cyclodextrines as functional agents for decontamination of the skin contaminated by nerve agents.

    PubMed

    Cabal, Jirí; Kuca, Kamil; Sevelová-Bartosová, Lucie; Dohnal, Vlastimil

    2004-01-01

    Three decontamination solutions of beta-cyclodextrines were prepared. Their abilities to decontamine rat skin contamined with nerve agent soman were tested. Decontamination efficacy of the tested cyclodextrine solutions was compared with the same decontamination means but without the cyclodextrines. The efficacy of tested decontaminants was evaluated by the assessment of the ID50 values. Two decontamination prescriptions with cyclodextrines (tetraborate buffer and tetraborate buffer with acetone) do not show significantly better decontamination efficacies in comparison with prescriptions without cyclodextrines. Only in case of aqueous solution of 2-aminoethanol the addition of beta-cyclodextrine resulted in significant increase (32%) in decontamination efficacy. PMID:15446361

  9. Effect of 2-hydroxypropyl-beta-cyclodextrin on the solubility, stability, and pharmacological activity of the chemical delivery system of TRH analogs.

    PubMed

    Wu, W M; Wu, J; Bodor, N

    2002-02-01

    To improve the aqueous solubility and stability of the chemical delivery system (CDS) of the thyrotropin-releasing hormone (TRH) analogs, 2-hydroxypropyl-beta-cyclodextrin (HPBCD) has been attempted. TRH analogs were [Leu2]-TRH, [Nva2]-TRH and [Nva2, Pip3]-TRH. Excess amount of CDS was added in various HPBCD in water solutions (0%-50%, pH 6.5). The mixture was saturated by ultra-sonication for 1 h at 15 degrees C and filtered. The concentration of CDS in the filtrate (solubility) was determined with UV detector, and subsequently the stability was investigated. By HPBCD complexation, the aqueous solubility and stability (half-life) of CDS were significantly improved from undetectable levels to about 15 mg/ml and 30 h, respectively. In pH 6.5 and 7.4 HPBCD solution, the degradation of CDS was mainly via acid catalyzed water addition reaction, thus, e.g. [Leu2]-TRH-CDS was more stable in pH 7.4 than in pH 6.5 aqueous solutions. After lyophilizing the saturated CDSs in 50% HPBCD complex solutions, the amount of CDS in the complex was determined as 26.22, 26.79, and 30.34 mg/g for [Leu2]-TRH, [Nva2]-TRH and [Nva2, Pip3]-TRH, respectively. The half-life of [Leu2]-TRH-CDS/HPBCD solid complex at 25 degrees C, 4 degrees C and -15 degrees C was about 100 days, 440 days and no detectable change in three months, respectively. Argon protected condition did not improve the stability of lyophilized [Leu2]-TRH-CDS/HPBCD complex. Dimethyl sulfoxide although increased the solubility of [Leu2]-TRH-CDS in the 50% HPBCD solution by 1.3 times, significantly decreased its stability by 6.6 times. After intravenous administration of CDS (in 30% HPBCD) at a dose of 10 mumole/kg in mice, compared to the vehicle control or the same dose of [Leu2]-TRH (in 30% HPBCD), a significant increase in pharmacological effect (decrease in barbiturate-induced sleeping time) was observed. These results demonstrate the usefulness of cyclodextrin in the formulation of the CDSs of TRH analogs. PMID:11878189

  10. Enzymatic production of cyclodextrins.

    PubMed

    Biwer, A; Antranikian, G; Heinzle, E

    2002-09-01

    Cyclodextrins (CD) are enzymatically modified starches with a wide range of applications in food, pharmaceutical and chemical industries, agriculture and environmental engineering. They are produced from starch via enzymatic conversion using cyclodextrin glycosyl transferases (CGTases) and partly alpha-amylases. Due to its low solubility in water, separation and purification of beta-CD is relatively easy compared to alpha- and gamma-CD. In recent years more economic processes for gamma-CD and especially alpha-CD production have been developed using improved CGTases and downstream processing. New purification steps, e.g. affinity adsorption, may reduce the use of complexing agents. The implementation of thermostable CGTases can simplify the production process and increase the selectivity of the reaction. A tabular overview of alpha-CD production processes is presented. PMID:12226716

  11. Predicting the binding free energy of the inclusion process of 2-hydroxypropyl-β-cyclodextrin and small molecules by means of the MM/3D-RISM method.

    PubMed

    Sugita, Masatake; Hirata, Fumio

    2016-09-28

    A protocol to calculate the binding free energy of a host-guest system is proposed based on the MM/3D-RISM method, taking cyclodextrin derivatives and their ligands as model systems. The protocol involves the procedure to identify the most probable binding mode (MPBM) of receptors and ligands by means of the umbrella sampling method. The binding free energies calculated by the MM/3D-RISM method for the complexes of the seven ligands with the MPBM of the cyclodextrin, and with the fluctuated structures around it, are in agreement with the corresponding experimental data in a semi-quantitative manner. It suggests that the protocol proposed here is promising for predicting the binding affinity of a small ligand to a relatively rigid receptor such as cyclodextrin. PMID:27452185

  12. Predicting the binding free energy of the inclusion process of 2-hydroxypropyl-β-cyclodextrin and small molecules by means of the MM/3D-RISM method

    NASA Astrophysics Data System (ADS)

    Sugita, Masatake; Hirata, Fumio

    2016-09-01

    A protocol to calculate the binding free energy of a host–guest system is proposed based on the MM/3D-RISM method, taking cyclodextrin derivatives and their ligands as model systems. The protocol involves the procedure to identify the most probable binding mode (MPBM) of receptors and ligands by means of the umbrella sampling method. The binding free energies calculated by the MM/3D-RISM method for the complexes of the seven ligands with the MPBM of the cyclodextrin, and with the fluctuated structures around it, are in agreement with the corresponding experimental data in a semi-quantitative manner. It suggests that the protocol proposed here is promising for predicting the binding affinity of a small ligand to a relatively rigid receptor such as cyclodextrin.

  13. Titanocene / cyclodextrin supramolecular systems: a theoretical approach

    PubMed Central

    2012-01-01

    lines. Conclusions According to our theoretical study, the titanocene/cyclodextrin inclusion compounds can be obtained (high interaction energy; the encapsulation is energetically favourable). Further, the most hydrophobic compounds are better encapsulated in β- and γ-cyclodextrin molecules and are more stable (from energetically point of view) in comparison with α-cyclodextrin case. This study suggests that the titanocene / β- and γ-cyclodextrin complexes (or synthetically modified cyclodextrins with higher water solubility) could be experimentally synthesized and could have enhanced cytotoxic activity and even lower toxicity. PMID:23122334

  14. Transdermal permeation modulation by cyclodextrins: a mechanistic study.

    PubMed

    Williams, A C; Shatri, S R; Barry, B W

    1998-08-01

    The purpose of this study was to investigate permeation modulation by beta- and 2-hydroxypropyl-beta-cyclodextrins (beta-CD and HP-beta-CD, respectively) alone and complexed with penetration enhancers for the test drugs 5-fluorouracil and estradiol through human skin, and to probe the value of the CDs in a barrier cream against toluene exposure. Methods include phase solubility studies, permeation experiments, and thermal analysis of stratum corneum; inclusion complexes were characterized by Karl Fischer titrimetry, infrared spectroscopy, and thermal analysis. Results show that complexes of terpenes or toluene with beta-CD were insoluble, whereas those with HP-beta-CD were soluble. The CDs did not enhance flux of either the polar or lipophilic drugs through skin; estradiol permeation was reduced following membrane pretreatment with either CD. Complexation of the lipophilic terpenes with the CDs reduced enhancer efficacy. When formulated into a barrier ointment both CDs, but particularly beta-CD, retarded toluene permeation through the skin and delayed the onset of maximum flux. It is concluded that the CDs themselves are not penetration enhancers for 5-fluorouracil or estradiol in human skin, and that they may be usefully incorporated into a barrier formulation to reduce percutaneous absorption of toxic materials on occupational exposure. PMID:9742549

  15. Efficacy of attractive toxic sugar baits (ATSB) against Aedes albopictus with garlic oil encapsulated in beta-cyclodextrin as the active ingredient

    PubMed Central

    Junnila, Amy; Revay, Edita E.; Müller, Gunter C.; Kravchenko, Vasiliy; Qualls, Whitney A.; Xue, Rui-de; Allen, Sandra A.; Beier, John C.; Schlein, Yosef

    2016-01-01

    We tested the efficacy of attractive toxic sugar bait (ATSB) with garlic oil microencapsulated in beta-cyclodextrin as active ingredient against Aedes albopictus in suburban Haifa, Israel. Two three-acre gardens with high numbers of Ae. albopictus were selected for perimeter spray treatment with ATSB and ASB (bait containing no active ingredient). Baits were colored with food dye to verify feeding of the mosquitoes. The mosquito population was monitored by human landing catches and sweep net catches in the surrounding vegetation. Experiments lasted for 44 days. Treatment occurred on day 13. The mosquito population collapsed about 4 days after treatment and continued to drop steadily for 27 days until the end of the study. At the experimental site the average pre-treatment landing rate was 17.2 per 5 mins. Two days post-treatment, the landing rate dropped to 11.4, and continued to drop to an average of 2.6 during the following 26 days. During the same period, the control population was stable. Few sugar fed females (8–10%) approached a human bait and anthrone tests showed relatively small amounts of sugar within their crop/gut. Around 60–70 % of males caught near our human bait were sugar positive which may indicate that the males were feeding on sugar for mating related behavior. From the vegetation treated with the toxic bait, we recovered significantly fewer (about 10–14%) males and females stained by ATSB than at the ASB-treated control. This may indicate that the toxic baits alter the resting behavior of the poisoned mosquitoes within the vegetation. Almost no Ae. albopictus females (5.2 ± 1.4) approached human bait after treatment with ATSB. It therefore appears that microencapsulated garlic oil is an effective pesticide against Ae. albopictus when used in an ATSB system. PMID:26403337

  16. Efficacy of attractive toxic sugar baits (ATSB) against Aedes albopictus with garlic oil encapsulated in beta-cyclodextrin as the active ingredient.

    PubMed

    Junnila, Amy; Revay, Edita E; Müller, Gunter C; Kravchenko, Vasiliy; Qualls, Whitney A; Xue, Rui-de; Allen, Sandra A; Beier, John C; Schlein, Yosef

    2015-12-01

    We tested the efficacy of attractive toxic sugar bait (ATSB) with garlic oil microencapsulated in beta-cyclodextrin as active ingredient against Aedes albopictus in suburban Haifa, Israel. Two three-acre gardens with high numbers of Ae. albopictus were selected for perimeter spray treatment with ATSB and ASB (bait containing no active ingredient). Baits were colored with food dye to verify feeding of the mosquitoes. The mosquito population was monitored by human landing catches and sweep net catches in the surrounding vegetation. Experiments lasted for 44 days. Treatment occurred on day 13. The mosquito population collapsed about 4 days after treatment and continued to drop steadily for 27 days until the end of the study. At the experimental site the average pre-treatment landing rate was 17.2 per 5mins. Two days post-treatment, the landing rate dropped to 11.4, and continued to drop to an average of 2.6 during the following 26 days. During the same period, the control population was stable. Few sugar fed females (8-10%) approached a human bait and anthrone tests showed relatively small amounts of sugar within their crop/gut. Around 60-70 % of males caught near our human bait were sugar positive which may indicate that the males were feeding on sugar for mating related behavior. From the vegetation treated with the toxic bait, we recovered significantly fewer (about 10-14%) males and females stained by ATSB than at the ASB-treated control. This may indicate that the toxic baits alter the resting behavior of the poisoned mosquitoes within the vegetation. Almost no Ae. albopictus females (5.2±1.4) approached human bait after treatment with ATSB. It therefore appears that microencapsulated garlic oil is an effective pesticide against Ae. albopictus when used in an ATSB system. PMID:26403337

  17. The formation and characterization of cyclodextrin functionalized polystyrene nanofibers produced by electrospinning.

    PubMed

    Uyar, Tamer; Havelund, Rasmus; Hacaloglu, Jale; Zhou, Xingfei; Besenbacher, Flemming; Kingshott, Peter

    2009-03-25

    Polystyrene (PS) nanofibers containing the inclusion complex forming beta-cyclodextrin (beta-CD) were successfully produced by electrospinning aimed at developing functional fibrous nanowebs. By optimization of the electrospinning parameters, which included varying the relative concentration of PS and beta-CD in the solutions, bead-free fibers were produced. Homogeneous solutions of beta-CD and PS in dimethylformamide (DMF) were used with concentrations of PS varying from 10% to 25% (w/v, with respect to DMF), and beta-CD concentrations of 1% to 50% (w/w, with respect to PS). The presence of beta-CD facilitated the production of bead-free PS fibers even from lower polymer concentrations as a result of the higher conductivity of the PS/CD solutions. The morphology and the production of bead-free PS/CD fibers were highly dependent on the beta-CD contents. Transmission electron microscope (TEM) and atomic force microscope (AFM) images showed that incorporation of beta-CD yielded PS fibers with rougher surfaces. Thermogravimetric analysis (TGA) and direct insertion probe pyrolysis mass spectroscopy (DP-MS) results confirmed the presence of beta-CD in the PS fibers. X-ray diffraction (XRD) spectra of the fibers indicated that the beta-CD molecules are distributed within the PS matrix without any phase separated crystalline aggregates up to 40% (w/w) beta-CD loading. Furthermore, chemical analyses by Fourier transform infrared (FTIR) spectroscopy studies confirm that beta-CD molecules are located within the PS fiber matrix. Finally, preliminary investigations using x-ray photoelectron spectroscopy (XPS) and time-of-flight static secondary ion mass spectrometry (ToF-static-SIMS) show the presence of the cyclodextrin molecules in the outer molecular layers of the fiber surfaces. The XPS and ToF-SIMS findings indicate that cyclodextrin functionalized PS webs would have the potential to be used as molecular filters and/or nanofilters for the purposes of filtration

  18. Self-assembly vesicles made from a cyclodextrin supramolecular complex.

    PubMed

    Jing, Bo; Chen, Xiao; Wang, Xudong; Yang, Chunjie; Xie, Yizhou; Qiu, Huayu

    2007-01-01

    Self-assembly vesicles have been made from a cyclodextrin (CD) supramolecular complex, which is cooperatively formed with natural beta-CD, 1-naphthylammonium chloride (NA), and sodium bis(2-ethyl-1-hexyl)sulfosuccinate (AOT) by weak noncovalent interactions. In the complex structure, a NA molecule is included inside a beta-CD molecule while it is coupled with an AOT molecule on one side. The supramolecular structure and morphology of the vesicles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. The mechanism of vesicle formation and transition is discussed along with the data obtained from induced circular dichroism (ICD) and UV/visible spectroscopy, polarized optical microscopy (POM), and (1)H NMR spectroscopy. Both the fabrication and the transition of vesicles are controlled by the inclusion equilibria and the cooperative binding of noncovalent interactions, which include the "key-lock" principle, electrostatic interactions, pi-pi stacking, and amphiphilic hydrophobic association. PMID:17663495

  19. Bioadhesive properties and biodistribution of cyclodextrin-poly(anhydride) nanoparticles.

    PubMed

    Agüeros, Maite; Areses, Paloma; Campanero, Miguel Angel; Salman, Hesham; Quincoces, Gemma; Peñuelas, Ivan; Irache, Juan Manuel

    2009-06-28

    This work describes the preparation, characterization and evaluation of the nanoparticles formed by the copolymer of methyl vinyl ether and maleic anhydride (Gantrez) AN) and cyclodextrins, including beta-cyclodextrin (CD) hydroxypropyl-beta-cyclodextrin (HPCD) and 6-monodeoxy-6-monoamino-beta-cyclodextrin (NHCD). The cyclodextrin-poly(anhydride) nanoparticles were prepared by a solvent displacement method and characterized by measuring the size, zeta potential, morphology and composition. For bioadhesion studies, nanoparticles were fluorescently labelled with rhodamine B isothiocianate (RBITC). For in vivo imaging biodistribution studies, (99m)Tc-labelled nanoparticles were used. Nanoparticles displayed a size of about 150nm and a cyclodextrin content which was found optimal under the following experimental conditions: cyclodextrin/poly(anhydride) ratio of 0.25 by weight, 30min of incubation time between the cyclodextrin and the polymer. Moreover, the oligosaccharide content was higher with CD than with NHCD and HPCD. Overall, cyclodextrin-poly(anhydride) nanoparticles displayed homogeneous bioadhesive interactions within the gut. The intensity of these interactions was higher than for control nanoparticles. The high bioadhesive capacity was observed for HPCD-NP and NHCD-NP which can be related with their rough morphology and, thus, a higher specific surface than for smooth nanoparticles (CD-NP). Finally, from in vivo studies, no evidence of translocation of distribution to other organs was observed when these nanoparticles were orally administered. PMID:19491010

  20. Peripheral substitution of pheophorbides and bacteriopheophorbides to promote inclusion into inert carrier systems for PDT

    NASA Astrophysics Data System (ADS)

    Roehrs, Susanne; Ruebner-Heuermann, Anja; Hartwich, G.; Scheer, H.; Moser, Joerg G.

    1996-01-01

    Pheophorbide a ethyl ester, pyropheophorbide a ethyl ester, and bacteriopheophorbide ethyl ester were substituted in 31-position with tert.butyl phenoxy or tert.butyl benzoic acid ester groups resp. in order to enhance affinity to (beta) -cyclodextrin dimers which form inclusion complexes with these photosensitizing drugs. This is a first step to construct inert transport complexes in order to photosensitize specifically cancer cells.

  1. Preparation, Characterization, and Pharmacological Activity of Cymbopogon winterianus Jowitt ex Bor (Poaceae) Leaf Essential Oil of β-Cyclodextrin Inclusion Complexes

    PubMed Central

    Santos, Priscila L.; Araújo, Adriano A. S.; Quintans, Jullyana S. S.; Oliveira, Makson G. B.; Brito, Renan G.; Serafini, Mairim R.; Menezes, Paula P.; Santos, Marcio R. V.; Alves, Pericles B.; de Lucca Júnior, Waldecy; Blank, Arie F.; La Rocca, Viviana; Almeida, Reinaldo N.; Quintans-Júnior, Lucindo J.

    2015-01-01

    This study aimed to evaluate the orofacial antinociceptive effect of the Cymbopogon winterianus essential oil (LEO) complexed in β-cyclodextrin (LEO-CD) and to assess the possible involvement of the central nervous system (CNS). The LEO was extracted, chromatographed, and complexed in β-cyclodextrin. The complex was characterized by differential scanning calorimetry (DSC) and thermogravimetry derivative (TG/DTG). Male Swiss mice (2-3 months) were treated with LEO-CD (50–200 mg/kg, p.o.), vehicle (distilled water, p.o.), or standard drug (i.p.) and subjected to the orofacial nociception formalin-, capsaicin-, and glutamate-induced. After the formalin test, the animals were perfused and the brains subjected to immunofluorescence for Fos. The rota-rod test (7 rpm/min) was carried out. Geraniol (37.57%) was the main compound of LEO. DSC and TG/DTG proved the complexation. The orofacial nociceptive behavior was significantly (p < 0.05) reduced. The number of Fos-positive cells was significantly changed in the dorsal raphe nucleus (p < 0.01), locus coeruleus (p < 0.001), trigeminal nucleus (p < 0.05), and trigeminal thalamic tract (p < 0.05). LEO-CD did not cause changes in motor coordination in the rota-rod test. Thus, our results suggested that LEO-CD has an orofacial antinociceptive profile, probably mediated by the activation of the CNS without changing the motor coordination. PMID:26246838

  2. Preparation, Characterization, and Pharmacological Activity of Cymbopogon winterianus Jowitt ex Bor (Poaceae) Leaf Essential Oil of β-Cyclodextrin Inclusion Complexes.

    PubMed

    Santos, Priscila L; Araújo, Adriano A S; Quintans, Jullyana S S; Oliveira, Makson G B; Brito, Renan G; Serafini, Mairim R; Menezes, Paula P; Santos, Marcio R V; Alves, Pericles B; de Lucca Júnior, Waldecy; Blank, Arie F; La Rocca, Viviana; Almeida, Reinaldo N; Quintans-Júnior, Lucindo J

    2015-01-01

    This study aimed to evaluate the orofacial antinociceptive effect of the Cymbopogon winterianus essential oil (LEO) complexed in β-cyclodextrin (LEO-CD) and to assess the possible involvement of the central nervous system (CNS). The LEO was extracted, chromatographed, and complexed in β-cyclodextrin. The complex was characterized by differential scanning calorimetry (DSC) and thermogravimetry derivative (TG/DTG). Male Swiss mice (2-3 months) were treated with LEO-CD (50-200 mg/kg, p.o.), vehicle (distilled water, p.o.), or standard drug (i.p.) and subjected to the orofacial nociception formalin-, capsaicin-, and glutamate-induced. After the formalin test, the animals were perfused and the brains subjected to immunofluorescence for Fos. The rota-rod test (7 rpm/min) was carried out. Geraniol (37.57%) was the main compound of LEO. DSC and TG/DTG proved the complexation. The orofacial nociceptive behavior was significantly (p < 0.05) reduced. The number of Fos-positive cells was significantly changed in the dorsal raphe nucleus (p < 0.01), locus coeruleus (p < 0.001), trigeminal nucleus (p < 0.05), and trigeminal thalamic tract (p < 0.05). LEO-CD did not cause changes in motor coordination in the rota-rod test. Thus, our results suggested that LEO-CD has an orofacial antinociceptive profile, probably mediated by the activation of the CNS without changing the motor coordination. PMID:26246838

  3. Inclusion Complex of Zerumbone with Hydroxypropyl- β -Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio.

    PubMed

    Muhammad Nadzri, Nabilah; Abdul, Ahmad Bustamam; Sukari, Mohd Aspollah; Abdelwahab, Siddig Ibrahim; Eid, Eltayeb E M; Mohan, Syam; Kamalidehghan, Behnam; Anasamy, Theebaa; Ng, Kuan Beng; Syam, Suvitha; Arbab, Ismail Adam; Rahman, Heshu Sulaiman; Ali, Hapipah Mohd

    2013-01-01

    Zerumbone (ZER) isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl- β -cyclodextrin (HP β CD) to enhance ZER's solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HP β CD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HP β CD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HP β CD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans. PMID:23737847

  4. Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

    PubMed Central

    Abdul, Ahmad Bustamam; Sukari, Mohd Aspollah; Abdelwahab, Siddig Ibrahim; Eid, Eltayeb E. M.; Kamalidehghan, Behnam; Anasamy, Theebaa; Ng, Kuan Beng; Syam, Suvitha; Arbab, Ismail Adam; Rahman, Heshu Sulaiman; Ali, Hapipah Mohd

    2013-01-01

    Zerumbone (ZER) isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD) to enhance ZER's solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans. PMID:23737847

  5. A 1H NMR titration study on the binding constants for D- and L-tryptophan inclusion complexes with 6-O-α-D-glucosyl-β-cyclodextrin. Formation of 1:1 and 2:1 (host:guest) complexes

    NASA Astrophysics Data System (ADS)

    Akita, Tomoki; Matsui, Yoshihisa; Yamamoto, Tatsuyuki

    2014-02-01

    A 1H NMR titration study revealed that 6-O-α-D-glucosyl-β-cyclodextrin (G1-β-CD) forms 1:1 and 2:1 (host:guest) inclusion complexes with D- and L-tryptophan in alkaline D2O solutions (pD 11.0). The binding constants (K1's) for the 1:1 complexes of D-isomer at 298 K (59 mol-1 dm3) were virtually equal to that of L-isomer (54 mol-1 dm3). On the other hand, the K2 values for 2:1 complexes of D-isomer (42 mol-1 dm3) were larger than that of L-counterpart (12 mol-1 dm3). These facts suggest that the first CD molecule includes the indole ring moiety of tryptophan, followed by inclusion with the second CD molecule in the vicinity of chiral center, α-carbon of the guest, to result in the difference in K2's for two enantiomers. Two-dimensional NMR measurement (Rotating-frame nuclear Overhauser Effect SpectroscopY, ROESY) supported this interpretation.

  6. Bioengineering of a cellulosic fabric for insecticide delivery via grafted cyclodextrin.

    PubMed

    Romi, Roberto; Lo Nostro, Pierandrea; Bocci, Eugenio; Ridi, Francesca; Baglioni, Piero

    2005-01-01

    beta-Cyclodextrin (beta-CD) can be easily grafted onto cellulosic textiles through covalent bonds. In such a way beta-CD empty cavities provide an efficient tool for entrapping different kinds of hydrophobic molecules on the surface of the fabric and releasing them slowly in time. The capability of cyclodextrins to include hydrophobic molecules such as fragrances, antimicrobial agents, and other chemicals can be then exploited to produce new grafted textiles with peculiar and useful performances. In this work we report the inclusion of two different products, the pyrethroid insecticide permethrin (PERM) and the insect repellent N,N-diethyl-m-toluamide (DEET), into beta-CD molecules grafted on cotton fabric. UV-vis spectrophotometry and thermal analysis confirmed the presence of the guest molecules on the fabric surface. Bioassays were carried out on two mosquito species of medical importance, Aedes aegypti and Anopheles stephensi; knock down effect and mortality were measured using standard World Health Organization (WHO) cone tests. Repellency and irritancy (blood feeding inhibition) were also measured using cage tests and a baited tunnel device. PERM-treated fabrics kept the insecticidal/irritant efficacy even for a long time after the treatment, whereas DEET activity lasted more shortly. PMID:16321057

  7. Supramolecular self-assembly of cyclodextrin and higher water soluble guest: thermodynamics and topological studies.

    PubMed

    De Sousa, Frederico B; Denadai, Angelo M Leite; Lula, Ivana S; Nascimento, Clebio S; Fernandes Neto, Nathália S G; Lima, Ana C; De Almeida, Wagner B; Sinisterra, Rubén D

    2008-07-01

    The supramolecular interactions between Imipramine hydrochloride (IMI), a tricyclic antidepressant, and beta-cyclodextrin (betaCD) have been investigated by experimental techniques and theoretical calculations. The association between these molecules might be lead to a host/guest compound, in which the physical chemistry properties of the guest molecule, such as high solubility, can be decreased. These new properties acquired by the inclusion phenomena are important to develop a strategy for pharmaceutical formulation. Nuclear magnetic resonance and horizontal attenuated total reflectance provided relevant information on the complex stoichiometries and the sites of interactions between the host and guest molecules. Stoichiometries of 1:2, 1:1, and 2:1 betaCD/IMI have been detected in solution. Self-diffusion coefficient and dynamic light scattering analysis provided information on the self-aggregation of the complex. Also, isothermal titration calorimetry studies indicated the existence of equilibrium between different complexes in solution. In order to determine the preferred arrangement for the inclusion complex formed by the IMI molecule and betaCD, theoretical calculations were performed. Of all proposed supramolecular structures, the 2:1 betaCD/IMI complex was calculated to be the most energetically favorable, in both gas and aqueous phases. The calculations indicated that the intermolecular hydrogen bonds involving the hydroxyl groups of betaCD play a major role in stabilizing the supramolecular 2:1 structure, corroborating experimental findings. PMID:18529008

  8. Cooperation between two ClpB isoforms enhances the recovery of the recombinant {beta}-galactosidase from inclusion bodies

    SciTech Connect

    Guenther, Izabela; Zolkiewski, Michal; Kedzierska-Mieszkowska, Sabina

    2012-10-05

    Highlights: Black-Right-Pointing-Pointer An important role of synergistic cooperation between the two ClpB isoforms. Black-Right-Pointing-Pointer Both ClpB isoforms are associated with IBs of {beta}-galactosidase. Black-Right-Pointing-Pointer ClpB is a key chaperone in IB protein release. -- Abstract: Bacterial ClpB is a molecular chaperone that solubilizes and reactivates aggregated proteins in cooperation with the DnaK chaperone system. The mechanism of protein disaggregation mediated by ClpB is linked to translocation of substrates through the central channel within the ring-hexameric structure of ClpB. Two isoforms of ClpB are produced in vivo: the full-length ClpB95 and the truncated ClpB80 (ClpB{Delta}N), which does not contain the N-terminal domain. The functional specificity of the two ClpB isoforms and the biological role of the N-terminal domain are still not fully understood. Recently, it has been demonstrated that ClpB may achieve its full potential as an aggregate-reactivating chaperone through the functional interaction and synergistic cooperation of its two isoforms. It has been found that the most efficient resolubilization and reactivation of stress-aggregated proteins occurred in the presence of both ClpB95 and ClpB80. In this work, we asked if the two ClpB isoforms functionally cooperate in the solubilization and reactivation of proteins from insoluble inclusion bodies (IBs) in Escherichia coli cells. Using the model {beta}-galactosidase fusion protein (VP1LAC), we found that solubilization and reactivation of enzymes entrapped in IBs occurred more efficiently in the presence of ClpB95 with ClpB80 than with either ClpB95 or ClpB80 alone. The two isoforms of ClpB chaperone acting together enhanced the solubility and enzymatic activity of {beta}-galactosidase sequestered into IBs. Both ClpB isoforms were associated with IBs of {beta}-galactosidase, what demonstrates their affinity to this type of aggregates. These results demonstrate a synergistic

  9. Encapsulation of CO2 into amorphous alpha-cyclodextrin powder at different moisture contents - Part 1: Encapsulation capacity and stability of inclusion complexes.

    PubMed

    Ho, Thao M; Howes, Tony; Bhandari, Bhesh R

    2016-07-15

    This study investigated the effects of water-induced crystallization of amorphous alpha-cyclodextrin (α-CD) powder on CO2 encapsulation at 0.4-1.6 MPa pressure for 1-72 h through the addition of water (to reach to 13, 15 and 17% wet basis, w.b.) into amorphous α-CD powder prior to the encapsulation. The results showed that the α-CD encapsulation capacity was over 1 mol CO2/mol α-CD after pressurizing for longer than 48 h. The encapsulated CO2 concentration by the addition of water was considerably higher (p<0.05) than that of amorphous α-CD powder (5.51% MC, w.b.) without an addition of water and that of crystalline α-CD powders under the same MC and encapsulation conditions. A comparison of CO2 release properties (75% relative humidity, 25 °C) from complexed powders prepared from amorphous and crystalline α-CD powders under the same conditions is also presented. PMID:26948624

  10. The sensitive capillary electrophoretic-LIF method for simultaneous determination of curcuminoids in turmeric by enhancing fluorescence intensities of molecules upon inclusion into (2-hydroxypropyl)-β-cyclodextrin.

    PubMed

    Kalaycıoğlu, Zeynep; Hashemi, Parya; Günaydın, Keriman; Erim, F Bedia

    2015-10-01

    Curcuminoids have received great attention in the past decades due to their health benefit properties. The aim of this study is to develop a very simple, rapid, and sensitive capillary zone electrophoresis technique coupled with a laser induced fluorescence detector (LIF) for the simultaneous determination of three major curcuminoids of turmeric, namely, curcumin, demethoxy curcumin (DMC), and bisdemethoxy curcumin (BDMC). Background electrolyte was selected as borate at pH 9.6 and (2-hydroxypropyl)-β-cyclodextrin (2-HP-β-CD) was added to prevent rapid alkali degradation of curcuminoids in buffer and to increase fluorescence intensities of molecules. With the addition of 2-HP-β-CD to the separation electrolyte, the fluorescence signal intensities of curcuminoids were enhanced considerably by 30, 40, and 54 fold for curcumin, DMC, and BDMC, respectively. The three curcuminoids of turmeric were fully separated and quantified in less than 4.5 min. The repeatability of the peak areas of curcuminoids for intra-day and inter-day experiments was in the satisfactory range of 2.26 and 2.55%, respectively. The LOD and LOQ values for the developed method were equal to or less than 0.081 and 0.270 μg/mL, respectively, for all curcuminoids. The developed method was successfully applied to find curcuminoids amount in turmeric samples and herbal supplements. PMID:26178140

  11. Repellent effects of Melaleuca alternifolia (tea tree) oil against cattle tick larvae (Rhipicephalus australis) when formulated as emulsions and in β-cyclodextrin inclusion complexes.

    PubMed

    Yim, Wei Tsun; Bhandari, Bhesh; Jackson, Louise; James, Peter

    2016-07-30

    Rhipicephalus australis (formerly Boophilus microplus) is a one host tick responsible for major economic loss in tropical and subtropical cattle production enterprises. Control is largely dependent on the application of acaricides but resistance has developed to most currently registered chemical groups. Repellent compounds that prevent initial attachment of tick larvae offer a potential alternative to control with chemical toxicants. The repellent effects of Melaleuca alternifolia oil (TTO) emulsions and two β-cyclodextrin complex formulations, a slow release form (SR) and a modified faster release form (FR), were examined in a series of laboratory studies. Emulsions containing 4% and 5% TTO applied to cattle hair in laboratory studies completely repelled ascending tick larvae for 24h whereas 2% and 3% formulations provided 80% protection. At 48h, 5% TTO provided 78% repellency but lower concentrations repelled less than 60% of larvae. In a study conducted over 15 days, 3% TTO emulsion applied to cattle hair provided close to 100% repellency for 2 days, but then protection fell to 23% by day 15. The FR formulation gave significantly greater repellency than the emulsion and the SR formulation from day 3 until the end of the study (P<0.05), providing almost complete repellency at day 3 (99.5%), then decreasing over the period of the study to 49% repellency at day 15. Proof of concept is established for the use of appropriately designed controlled-release formulations to extend the period of repellency provided by TTO against R. australis larvae. PMID:27369582

  12. (13)C and (15)N solid-state NMR studies on albendazole and cyclodextrin albendazole complexes.

    PubMed

    Ferreira, M João G; García, A; Leonardi, D; Salomon, Claudio J; Lamas, M Celina; Nunes, Teresa G

    2015-06-01

    (13)C and (15)N solid-state nuclear magnetic resonance (NMR) spectra were recorded from albendazole (ABZ) and from ABZ:β-cyclodextrin, ABZ:methyl-β-cyclodextrin, ABZ:hydroxypropyl-β-cyclodextrin and ABZ:citrate-β-cyclodextrin, which were prepared by the spray-drying technique. ABZ signals were typical of a crystalline solid for the pure drug and of an amorphous compound obtained from ABZ:cyclodextrin samples. Relevant spectral differences were correlated with chemical interaction between ABZ and cyclodextrins. The number and type of complexes revealed a strong dependence on the cyclodextrin group substituent. Solid-state NMR data were consistent with the presence of stable inclusion complexes. PMID:25843843

  13. Applications of cyclodextrins in medical textiles - review.

    PubMed

    Radu, Cezar-Doru; Parteni, Oana; Ochiuz, Lacramioara

    2016-02-28

    This paper presents data on the general properties and complexing ability of cyclodextrins and assessment methods (phase solubility, DSC tests and X-ray diffraction, FTIR spectra, analytical method). It focuses on the formation of drug deposits on the surface of a textile underlayer, using a cyclodextrin compound favoring the inclusion of a drug/active principle and its release onto the dermis of patients suffering from skin disorders, or for protection against insects. Moreover, it presents the kinetics, duration, diffusion flow and release media of the cyclodextrin drug for in vitro studies, as well as the release modeling of the active principle. The information focuses on therapies: antibacterial, anti-allergic, antifungal, chronic venous insufficiency, psoriasis and protection against insects. The pharmacodynamic agents/active ingredients used on cotton, woolen and synthetic textile fabrics are presented. PMID:26796039

  14. THE BINDING OF COCAINE TO CYCLODEXTRINS. (R826653)

    EPA Science Inventory

    Abstract

    Cocaine binds into beta.gif" alt="small beta, Greek" border=0>-cyclodextrin, but not detectably into small alpha, Greek

  15. Regioselective self-acylating cyclodextrins in organic solvent

    PubMed Central

    Cho, Eunae; Yun, Deokgyu; Jeong, Daham; Im, Jieun; Kim, Hyunki; Dindulkar, Someshwar D.; Choi, Youngjin; Jung, Seunho

    2016-01-01

    Amphiphilic cyclodextrins have been synthesized with self-acylating reaction using vinyl esters in dimethylformamide. In the present study no base, catalyst, or enzyme was used, and the structural analyses using thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry show that the cyclodextrin is substituted preferentially by one acyl moiety at the C2 position of the glucose unit, suggesting that cyclodextrin functions as a regioselective catalytic carbohydrate in organic solvent. In the self-acylation, the most acidic OH group at the 2-position and the inclusion complexing ability of cyclodextrin were considered to be significant. The substrate preference was also observed in favor of the long-chain acyl group, which could be attributed to the inclusion ability of cyclodextrin cavity. Furthermore, using the model amphiphilic building block, 2-O-mono-lauryl β-cyclodextrin, the self-organized supramolecular architecture with nano-vesicular morphology in water was investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. The cavity-type nano-assembled vesicle and the novel synthetic methods for the preparation of mono-acylated cyclodextrin should be of great interest with regard to drug/gene delivery systems, functional surfactants, and carbohydrate derivatization methods. PMID:27020946

  16. Regioselective self-acylating cyclodextrins in organic solvent.

    PubMed

    Cho, Eunae; Yun, Deokgyu; Jeong, Daham; Im, Jieun; Kim, Hyunki; Dindulkar, Someshwar D; Choi, Youngjin; Jung, Seunho

    2016-01-01

    Amphiphilic cyclodextrins have been synthesized with self-acylating reaction using vinyl esters in dimethylformamide. In the present study no base, catalyst, or enzyme was used, and the structural analyses using thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry show that the cyclodextrin is substituted preferentially by one acyl moiety at the C2 position of the glucose unit, suggesting that cyclodextrin functions as a regioselective catalytic carbohydrate in organic solvent. In the self-acylation, the most acidic OH group at the 2-position and the inclusion complexing ability of cyclodextrin were considered to be significant. The substrate preference was also observed in favor of the long-chain acyl group, which could be attributed to the inclusion ability of cyclodextrin cavity. Furthermore, using the model amphiphilic building block, 2-O-mono-lauryl β-cyclodextrin, the self-organized supramolecular architecture with nano-vesicular morphology in water was investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. The cavity-type nano-assembled vesicle and the novel synthetic methods for the preparation of mono-acylated cyclodextrin should be of great interest with regard to drug/gene delivery systems, functional surfactants, and carbohydrate derivatization methods. PMID:27020946

  17. Regioselective self-acylating cyclodextrins in organic solvent

    NASA Astrophysics Data System (ADS)

    Cho, Eunae; Yun, Deokgyu; Jeong, Daham; Im, Jieun; Kim, Hyunki; Dindulkar, Someshwar D.; Choi, Youngjin; Jung, Seunho

    2016-03-01

    Amphiphilic cyclodextrins have been synthesized with self-acylating reaction using vinyl esters in dimethylformamide. In the present study no base, catalyst, or enzyme was used, and the structural analyses using thin layer chromatography, nuclear magnetic resonance spectroscopy and mass spectrometry show that the cyclodextrin is substituted preferentially by one acyl moiety at the C2 position of the glucose unit, suggesting that cyclodextrin functions as a regioselective catalytic carbohydrate in organic solvent. In the self-acylation, the most acidic OH group at the 2-position and the inclusion complexing ability of cyclodextrin were considered to be significant. The substrate preference was also observed in favor of the long-chain acyl group, which could be attributed to the inclusion ability of cyclodextrin cavity. Furthermore, using the model amphiphilic building block, 2-O-mono-lauryl β-cyclodextrin, the self-organized supramolecular architecture with nano-vesicular morphology in water was investigated by fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. The cavity-type nano-assembled vesicle and the novel synthetic methods for the preparation of mono-acylated cyclodextrin should be of great interest with regard to drug/gene delivery systems, functional surfactants, and carbohydrate derivatization methods.

  18. Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs.

    PubMed

    Becker, Lisa F; Schwarz, Dennis H; Wenz, Gerhard

    2014-01-01

    Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially the β-cyclodextrin derivatives exhibit very high binding potentials towards the anaesthetic drugs sevoflurane and halothane. Since the resulting inclusion compounds are highly soluble in water at temperatures ≤37 °C they are good candidates for new aqueous dosage forms which would avoid inhalation anaesthesia. PMID:25550759

  19. Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

    PubMed Central

    Becker, Lisa F; Schwarz, Dennis H

    2014-01-01

    Summary Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic displacement reactions starting from the corresponding per-(6-deoxy-6-bromo)cyclodextrins. Further modification of all 2-OH positions by etherification with iodo terminated triethylene glycol monomethyl ether (and tetraethylene glycol monomethyl ether, respectively) furnished water-soluble hosts. Especially the β-cyclodextrin derivatives exhibit very high binding potentials towards the anaesthetic drugs sevoflurane and halothane. Since the resulting inclusion compounds are highly soluble in water at temperatures ≤37 °C they are good candidates for new aqueous dosage forms which would avoid inhalation anaesthesia. PMID:25550759

  20. Budesonide-hydroxypropyl-β-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels.

    PubMed

    Santos Akkari, Alessandra Cristina; Ramos Campos, Estefânia Vangelie; Keppler, Artur Franz; Fraceto, Leonardo Fernandes; de Paula, Eneida; Tófoli, Giovana Radomille; de Araujo, Daniele Ribeiro

    2016-02-01

    Budesonide (BUD) is a glucocorticoid widely used for the treatment of ulcerative colitis. In this work, we propose the study of the system BUD-HP-β-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-β-CD was confirmed by phase solubility studies (1:1 stoichiometry, Kc=8662.8 M(-1)), DSC, FTIR and microscopy analyzes. BUD solubility in simulated upper and lower colon fluids was improved in a dependence of HP-β-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-β-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (Tm) was not shifted, but sol-gel phase transition studies showed that in the presence of BUD, HP-β-CD or BUD:HP-β-CD complex, the association PL407-PL403 favored the gel formation close to the physiological temperature. Physico-chemical and in vitro release assays studies revealed no competitive displacement of BUD from the HP-β-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-β-CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis. PMID:26674842

  1. Cyclodextrin-based Polymeric Nanoparticles as Efficient Carriers for Anticancer Drugs.

    PubMed

    Duchene, Dominique; Cavalli, Roberta; Gref, Ruxandra

    2016-01-01

    Among the difficulties encountered in the treatment of cancer are the physico-chemical properties of the chemotherapeutic agents; in particular low water solubility and low stability, resulting in poor efficacy. Due to their capability to form molecular inclusions with apolar molecules (or part of them) cyclodextrins constitute a powerful tool to prepare more efficient chemotherapeutic delivery systems such as nanoparticles. This review focuses on polymeric nanoparticles for cancer therapy prepared from either cyclodextrin molecules, or polymer and cyclodextrins. PMID:26517333

  2. Influence of hydrophilic polymers on the complexation of carbamazepine with hydroxypropyl-β-cyclodextrin.

    PubMed

    Medarević, Djordje; Kachrimanis, Kyriakos; Djurić, Zorica; Ibrić, Svetlana

    2015-10-12

    In this study binary carbamazepine-hydroxypropyl-β-cyclodextrin, as well as ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were used to improve dissolution rate of carbamazepine. It has been shown that addition of hydrophilic polymers (Soluplus® and two types of hydroxypropyl methylcellulose-Metolose® 90SH-100 and Metolose® 65SH-1500) significantly increased solubilization capacity of hydroxypropyl-β-cyclodextrin for carbamazepine. Evaluation of carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer interactions using molecular modeling techniques showed interactions between carbamazepine, which dissociates from inclusion complexes and hydroxypropyl methylcellulose that can prevent crystallization of dissolved carbamazepine. These results can contribute to better understanding of drug-cyclodextrin-hydrophilic polymer interactions which are still not well understood. After evaluation of carbamazepine solubilization with hydroxypropyl-β-cyclodextrin and hydrophilic polymers, both binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-hydrophilic polymer systems were prepared by spray drying. The results of solid state characterization methods showed amorphous nature of carbamazepine in all spray dried systems, which together with the results of molecular modeling techniques indicates inclusion complex formation. Carbamazepine dissolution rate was significantly improved from spray dried formulations compared to pure drug. Binary carbamazepine-hydroxypropyl-β-cyclodextrin and ternary carbamazepine-hydroxypropyl-β-cyclodextrin-Soluplus® systems exhibited the fastest carbamazepine release, wherein the entire amount of carbamazepine was released during first 5 min. PMID:26255049

  3. γ-Cyclodextrin capped silver nanoparticles for molecular recognition and enhancement of antibacterial activity of chloramphenicol.

    PubMed

    Gannimani, Ramesh; Ramesh, Muthusamy; Mtambo, Sphamandla; Pillay, Karen; Soliman, Mahmoud E; Govender, Patrick

    2016-04-01

    Computational studies were conducted to identify the favourable formation of the inclusion complex of chloramphenicol with cyclodextrins. The results of molecular docking and molecular dynamics predicted the strongest interaction of chloramphenicol with γ-cyclodextrin. Further, the inclusion complex of chloramphenicol with γ-cyclodextrin was experimentally prepared and a phenomenon of inclusion was verified by using different characterization techniques such as thermogravimetric analysis, differential scanning calorimetry, (1)H nuclear magnetic resonance (NMR) and two dimensional nuclear overhauser effect spectroscopy (NOESY) experiments. From these results it was concluded that γ-cyclodextrins could be an appropriate cyclodextrin polymer which can be used to functionalize chloramphenicol on the surface of silver nanoparticles. In addition, γ-cyclodextrin capped silver nanoparticles were synthesized and characterized using UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray analysis (EDX), Fourier transform infrared spectroscopy (FTIR) and zeta potential analysis. Molecular recognition of chloramphenicol by these cyclodextrin capped silver nanoparticles was confirmed by surface enhanced raman spectroscopy (SERS) experiments. Synergistic antibacterial effect of chloramphenicol with γ-cyclodextrin capped silver nanoparticles was evaluated against Pseudomonas aeruginosa (ATCC 27853), Enterococcus faecalis (ATCC 5129), Klebsiella pneumoniae (ATCC 700603) and Staphylococcus aureus (ATCC 43300). The results from the antibacterial experiment were favourable thus allowing us to conclude that the approach of modifying organic drug molecules with cyclodextrin capped inorganic silver nanoparticles could help to enhance the antibacterial activity of them. PMID:26824520

  4. Functionalized β-cyclodextrin based potentiometric sensor for naproxen determination.

    PubMed

    Lenik, Joanna; Łyszczek, Renata

    2016-04-01

    Potentiometric sensors based on neutral β-cyclodextrins: (2-hydroxypropyl)-β-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin and anionic β-cyclodextrin: (2-hydroxy-3-N,N,N-trimethylamino)propyl-β-cyclodextrin chloride for naproxen are described. Inclusion complexes of naproxen with the above-mentioned cyclodextrins were studied using IR spectroscopy. The electrode surface was made from PVC membranes doped with the appropriate β-cyclodextrin as ionophores and quaternary ammonium chlorides as positive charge additives that were dispersed in plasticizers. The optimum membrane contains heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin, o-nitrophenyloctyl ether and tetraoctyl ammonium chloride as a lipophilic salt. The electrode is characterized by a Nernstian response slope of -59.0 ± 0.5 mV decade(-1) over the linear range of 5.0 × 10(-5)-1.0 × 10(-2) mol L(-1) and the detection limit 1.0 × 10(-5) mol L(-1), as well as the response time 10s. It can be used in the pH range 6.2-8.5 for 10 months without any considerable deterioration. Incorporation of β-cyclodextrins improved the electrode selectivity towards naproxen ions from several inorganic and organic interferents and some common drug excipients due to concovalent interactions (host molecule-guest molecule). The notable advantages of the naproxen-selective electrode include its high sensitivity, high selectivity, cost-effectiveness as well as accurate and comfortable application in drug analysis and milk samples. PMID:26838835

  5. Caging effects on the ground and excited states of 2,2'-bipyridine-3,3'-diol embedded in cyclodextrins.

    PubMed

    Abou-Zied, Osama K; Al-Hinai, Ashraf T

    2006-06-29

    The 2,2'-bipyridine-3,3'-diol (BP(OH)(2)) molecule shows unique spectroscopic features in water that may position it as a new biological probe. In an attempt to mimic biological environments, we explore in this paper the caging effects of cyclodextrins on the steady state spectra of BP(OH)(2). The caging effects of gamma-, beta-, and 2,6-di-O-methyl-beta-cyclodextrins (CDs) on the ground and excited state properties of BP(OH)(2) in aqueous solutions are investigated by steady state absorption and fluorescence spectroscopy, and by ab initio calculations. The stoichiometry of the three complexes was found to be 1:1 and the binding constants were estimated from the absorption and fluorescence spectra. In the case of gamma-CD, the large cavity size supports only small binding, whereas such binding increases in the cases of the smaller cavity sizes of beta-CD and 2,6-di-O-methyl-beta-CD. Maximum binding was measured in the case of 2,6-di-O-methyl-beta-CD due to the increased hydrophobicity of the host cavity. The unique absorption features of BP(OH)(2) in water show a dramatic decrease in intensity due to caging effects. The decrease in intensity correlates very well with the extent of binding and hydrophobicity of the host molecules. Similar results were also obtained from the fluorescence spectra. The calculated structure of the BP(OH)(2):beta-CD complex predicts that the inclusion of BP(OH)(2) is nearly axial and centered inside the beta-CD cavity. The BP(OH)(2) molecule maintains its dienol moiety in the complex with no possible hydrogen bonding with the host interior H-atoms. The results are discussed in light of the possible use of BP(OH)(2) as a water sensor in biological systems. PMID:16789770

  6. [Study on quantitative mechanism and the interference of the UV spectrum of HABS reduced by β-Cyclodextrin].

    PubMed

    Shi, Dong-Po; Yin, Xian-Qing; Zheng, Yan-Cheng; Chen, Wu; Fu, Jia-Xin; Ren, Zhao-Hua

    2014-09-01

    A novel ultraviolet absorption spectrometry method was developed for the quantitative determination of HABS by adding β-cyclodextrin with the molar ratio of 1:1 in strong interference aqueous solution. The results indicated that the effect of several common interfering flooding agents (SAS, OP-10, HPAM) on the determination of HABS could be greatly reduced in β- cyclodextrin aqueous solution. Thus, the determination errors of the determined HABS were less than 2.0% under strong inter- ference, and the detection limit (S/N==3) of the method could be also as high was 8.3-9.1 x 10(-4) mg · L(-1). Various characterization results including 1H-NMR, TG-DSC and FTIR showed the interaction between β-cyclodextrin and HABS. The results of H-NMR analysis showed that HABS molecule could enter into the interior of the cavity of β-cyclodextrin molecule. TG-DSC analysis exhibited that the stable inclusion of β-cyclodextrin and HABS could be automatically formed. The interactions between the functional groups of β-cyclodextrin and HABS were showed by FTIR analysis, which also exhibited that the stable inclusion could be formed by HABS entering from the narrow or the broad mouth of the β-cyclodextrin. The interference of the UV spectrum of HABS could be reduced by β-cyclodextrin since the interaction between β-cyclodextrin due to the interaction between β-cyclodextrin and HABS in the inclusion complex. PMID:25532345

  7. Synthesis and Evaluation of Cyclodextrin-based Polymers for Patulin Extraction from Aqueous Solutions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Patulin is a mycotoxin produced by fungi that contaminate fruits, juices, and other agricultural commodities. Sorption properties of polyurethane-beta-cyclodextrin polymers were evaluated for the ability to remove patulin from solutions, including apple juice. Freundlich isotherm analysis determin...

  8. Two novel ternary albendazole-cyclodextrin-polymer systems: dissolution, bioavailability and efficacy against Taenia crassiceps cysts.

    PubMed

    Palomares-Alonso, Francisca; González, Cesar Rivas; Bernad-Bernad, Ma Josefa; Montiel, María Dolores Castillo; Hernández, Guadalupe Palencia; González-Hernández, Iliana; Castro-Torres, Nelly; Estrada, Enrique Pinzón; Jung-Cook, Helgi

    2010-01-01

    The effect of two water-soluble polymers: pectin and polyvinylpyrrolidone in combination with beta-cyclodextrin, on the dissolution, bioavailability and cysticidal efficacy of albendazole was evaluated using a commercial suspension as reference product. The dissolution of the albendazole-beta-cyclodextrin-pectin formulation was slow and incomplete (44.7%). No statistical differences in C(max) and AUC were found between this formulation and the reference. Also its cysticidal efficacy (33%) was similar to the reference (38%). The albendazole-beta-cyclodextrin-polyvinylpyrrolidone formulation exhibited the highest dissolution rate (78.5%) and its bioavailability was also significantly increased (2.3-fold). In addition, the cysticidal activity of this formulation (83%) was greater than a commercial suspension. Our results suggest that the ternary system of albendazole-beta-cyclodextrin-polyvinylpyrrolidone could be a potential alternative for the treatment of systemic helmintic diseases and it is worth to continue its preclinical evaluation. PMID:19769931

  9. Formulation and characterisation of beads prepared from natural cyclodextrins and vegetable, mineral or synthetic oils.

    PubMed

    Trichard, L; Fattal, E; Le Bas, G; Duchêne, D; Grossiord, J-L; Bochot, A

    2008-04-16

    A continuous external shaking for 2.5 days of a mixture composed of alpha-cyclodextrin (6%), soybean oil (19.6%) and water (74.4%) resulted in a calibrated lipid carrier namely bead with a high fabrication yield. The purpose of this work was to explore the possibility to substitute alpha-cyclodextrin by other natural cyclodextrins, i.e. beta- and gamma-cyclodextrin and then soybean oil by mineral (Primol) 352 and Marcol 82) or synthetic (Silicon 200) fluid 10, 50 or 100cSt) oils. Beads can be successfully prepared using Marcol 82 with alpha-cyclodextrin and Silicon 50 or 100cSt with gamma-cyclodextrin. The area inside oil/cyclodextrin/water ternary diagram corresponding to bead occurrence was superior for the Marcol 82/alpha-cyclodextrin couple compared to that observed with soybean oil/alpha-cyclodextrin couple. Only a few ratios of Silicon 50 and 100cSt/gamma-cyclodextrin/water led to beads. The combinations which did not induce bead occurrence gave either emulsions, two non-miscible liquids or a solid mixture. Whatever the materials used, beads exhibited similarities: presence of a crystalline organisation and viscoelastic properties. Manufacturing process of paraffin- and silicon-based beads need further optimisation to increase fabrication yield and later on, to take advantages from the high stability of both oils for the formulation of drugs with beads. PMID:18063325

  10. Preparation and characterization of amorphous solid dispersions of nimesulide in cyclodextrin copolymers.

    PubMed

    Skiba, M; Skiba, M; Milon, N; Bounoure, F; Fessi, H

    2014-04-01

    A study to enhance the dissolution rate of nimesulide (NIM), a poorly water-soluble, non-steroidal anti-inflammatory drug, was carried out through developing new amorphous solid dispersions (ASD) based on soluble or insoluble water cyclodextrin copolymers (alpha-cyclodextrin, beta-cyclodextrin and y-cyclodextrin polymers) synthesized by direct melt polycondensation. Amorphous solid dispersions of NIM in cyclodextrin copolymers, obtained by solvent evaporation, were characterized by thermogravimetric analyzer (TGA), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and fourier transform-infrared spectroscopy (FT-IR). These analyses provided the existence of interactions between amorphous drug and its carrier. A burst release of more than 80% NIM within approximately 70 minutes was seen with soluble alpha-cyclodextrin polymers (poly-alpha-sol) and insoluble gamma-cyclodextrin polymers (poly-gamma-insol) where no significant differences were observed with the other copolymers. Mathematical kinetic models such as zero order, Higuchi and Korsmeyer-Peppas were used to evaluate the kinetic and mechanism of release of NIM from the different ASD compared to lactose reference matrix. The kinetic of release of NIM from different ASD followed a Higuchi model and the mechanism of release was explained by Korsmeyer-Peppas model in which a fickian diffusion for lactose and soluble beta-cyclodextrin polymers (poly-beta-sol) was observed. However, an anomalous non-Fickian transport was found for the other copolymers. PMID:24734689

  11. Separation of vinca alkaloid enantiomers by capillary electrophoresis applying cyclodextrin derivatives and characterization of cyclodextrin complexes by nuclear magnetic resonance spectroscopy.

    PubMed

    Sohajda, Tamás; Varga, Erzsébet; Iványi, Róbert; Fejos, Ida; Szente, Lajos; Noszál, Béla; Béni, Szabolcs

    2010-12-15

    In this work, the enantiomeric separation of three vinca alkaloid enantiomers (vincamine, vinpocetine and vincadifformine) has been investigated in an aqueous capillary electrophoresis (CE) system using cyclodextrins (CDs). The investigated CDs were the native alpha-, beta-, and gamma-CDs and their hydroxypropylated, randomly methylated, carboxymethylated and sulfobutylated derivatives. The first part of this study consisted of the determination of the apparent averaged complex stability constants with the selected CDs. Several parameters, such as the nature and the concentration of the CD, were studied and were found to have a significant effect on the enantiomeric resolution for all studied compounds. All three vinca alkaloids were successfully enantioseparated with CDs where different migration orders were observed in case of several CDs depending on the cavity size or substituent of the host. Chiral separation and determination of the stability constants were also performed with NMR spectroscopy which confirmed the CE results. Averaged stoichiometries of the complexes were determined using the Job plot method resulting in a 1:1 complex irrespective of the alkaloid enantiomers or cyclodextrin derivative. The structures of the inclusion complexes were elucidated using 2D ROESY NMR spectroscopy. On the basis of NMR results reversal of enantiomer migration order was clarified in various cases. PMID:20724093

  12. Analytical techniques for characterization of cyclodextrin complexes in the solid state: A review.

    PubMed

    Mura, Paola

    2015-09-10

    Cyclodextrins are cyclic oligosaccharides able to form inclusion complexes with a variety of hydrophobic guest molecules, positively modifying their physicochemical properties. A thorough analytical characterization of cyclodextrin complexes is of fundamental importance to provide an adequate support in selection of the most suitable cyclodextrin for each guest molecule, and also in view of possible future patenting and marketing of drug-cyclodextrin formulations. The demonstration of the actual formation of a drug-cyclodextrin inclusion complex in solution does not guarantee its existence also in the solid state. Moreover, the technique used to prepare the solid complex can strongly influence the properties of the final product. Therefore, an appropriate characterization of the drug-cyclodextrin solid systems obtained has also a key role in driving in the choice of the most effective preparation method, able to maximize host-guest interactions. The analytical characterization of drug-cyclodextrin solid systems and the assessment of the actual inclusion complex formation is not a simple task and involves the combined use of several analytical techniques, whose results have to be evaluated together. The objective of the present review is to present a general prospect of the principal analytical techniques which can be employed for a suitable characterization of drug-cyclodextrin systems in the solid state, evidencing their respective potential advantages and limits. The applications of each examined technique are described and discussed by pertinent examples from literature. PMID:25743620

  13. Comparison of host-guest Langmuir-Blodgett multilayer formation by two different amphiphilic cyclodextrins

    SciTech Connect

    Parazak, D.P.; Khan, A.R.; D`Souza, V.T.; Stine, K.J.

    1996-08-07

    We report here our results for Langmuir monolayers of the derivatives of cyclodextrin shown: hexakis(6-deoxy-6-dodecylamino)-{alpha}-cyclodextrin (1a), heptakis(6-deoxy-6-dodecylamino)-{beta}-cyclodextrin (1b), and heptakis(6-deoxy-6-dodecylthio)-{beta}-cyclodextrin (2b ), which was found to be partially substituted. Langmuir films of these derivatives were examined using {Pi}-A isotherm measurements and Brewster angle microscopy. Langmuir-Blodgett (LB) multilayer films of these derivatives were deposited from subphases containing p-nitrophenol to determine the extent of incorporation of the guest molecule in the LB film. The transfer ratios of the film exhibited a noteworthy evolution with the transfer pressure. The variation in the extent of guest molecule incorporation is discussed and compared with the binding behavior in solution of unmodified cyclodextrins. 29 refs., 4 figs.

  14. Separation and characterization of modified pregabalins in terms of cyclodextrin complexation, using capillary electrophoresis and nuclear magnetic resonance.

    PubMed

    Béni, Szabolcs; Sohajda, Tamás; Neumajer, Gábor; Iványi, Róbert; Szente, Lajos; Noszál, Béla

    2010-03-11

    The (S)-(+)-isomer of 3-isobutyl-GABA (pregabalin), the blockbuster drug in the treatment of neuropathic pain has been separated from its R isomer by cyclodextrin modified capillary zone electrophoresis (CZE) using uncoated fused-silica capillary. Derivatization of the single isomer and the racemate with tosyl- and dansyl-chloride was carried out to introduce strong UV chromophores of different size. CE-pH titrations were performed to determine the dissociation constants for both derivatives. 30 cyclodextrin (CD) derivatives as chiral agents were used at four different pH values to study the enantioseparation of the differently protonated guest molecules. The separation was optimized as a function of CD concentration, buffer type and concentration, pH and applied voltage. For the tosylated derivate the best resolution (R(s)=2.76) was found with 6-monodeoxy-6-mono-(3-hydroxy)-propylamino-beta-cyclodextrin hydrochloride (PA-beta-CD) at pH 6.8, while with the same selector at pH 7.2 enantioseparation with an R(s) value of 4.32 could be achieved for the dansylated pregabalin. At pH 2.5 for the dansylated derivative trimethylated alpha- and beta-CD systems resulted the most significant separation (R(s)=7.38 and R(s)=7.74, respectively). Experiments with dual CD systems were carried out as well. The stoichiometry of the complexes was determined using the Job plot method and resulted in a 1:1 complex in both cases. The structures of the inclusion complexes were elucidated using 2D ROESY NMR experiments. PMID:19914021

  15. Cyclodextrins and antioxidants.

    PubMed

    López-Nicolás, José Manuel; Rodríguez-Bonilla, Pilar; García-Carmona, Francisco

    2014-01-01

    In recent years, the growth of the functional foods industry has increased research into new compounds with high added value for use in the fortification of traditional products. One of the most promising functional food groups is those enriched in antioxidant compounds of a lipophilic nature. In spite of the numerous advantages reported for such antioxidant molecules, they may also have disadvantages that impede their use in functional foods, although these problems may well avoided by the use of encapsulant agents such as cyclodextrins. This explains the recent increase in the number of research papers dealing with the complexation of different guest molecules possesing important antioxidant properties using natural and modified cyclodextrins. This paper presents a review of the most recent studies on the complexes formed between several important types of antioxidant compounds and cyclodextrins, focusing on the contradictory data reported in the literature concerning to the antioxidant activity of the host/guest molecule complexes, the different complexation constants reported for identical complexes, the bioavailability of the antioxidant compound in the presence of cyclodextrins and recommendation concerning the use of natural or modified cyclodextrins. Moreover, the use of cyclodextrins as antibrowning agents to prevent enzymatic browning in different foods is revised. Finally, we look at studies which suggest that cyclodextrins act as ''secondary antioxidants," enhancing the ability of traditional antioxidants to prevent enzymatic browning. PMID:24188271

  16. Spectroscopic investigation of the interaction between β-cyclodextrin and ascorbic acid

    NASA Astrophysics Data System (ADS)

    Bratu, Ioan; Muresan-Pop, Marieta; Kacso, Irina; Fărcaş, Sorin I.

    2009-08-01

    Inclusion compound of vitamin C (ascorbic acid) with β-cyclodextrin (β-CD), prepared by different methods (kneading, co-precipitation and freeze-drying) has been caracterized by several spectroscopic techniques (FTIR, 1H NMR, UV-Vis), powder X-ray diffraction and DSC technique. Based on the chemical shifts observed in the 1H-NMR and on FTIR spectra the tentative conclusion is that vitamin C probably enters the cyclodextrin torus forming the inclusion complex.

  17. Electrokinetic remediation and microbial community shift of β-cyclodextrin-dissolved petroleum hydrocarbon-contaminated soil.

    PubMed

    Wan, Chunli; Du, Maoan; Lee, Duu-Jong; Yang, Xue; Ma, Wencheng; Zheng, Lina

    2011-03-01

    Electrokinetic (EK) migration of β-cyclodextrin (β-CD), which is inclusive of total petroleum hydrocarbon (TPH), is an economically beneficial and environmentally friendly remediation process for oil-contaminated soils. Remediation studies of oil-contaminated soils generally prepared samples using particular TPHs. This study investigates the removal of TPHs from, and electromigration of microbial cells in field samples via EK remediation. Both TPH content and soil respiration declined after the EK remediation process. The strains in the original soil sample included Bacillus sp., Sporosarcina sp., Beta proteobacterium, Streptomyces sp., Pontibacter sp., Azorhizobium sp., Taxeobacter sp., and Williamsia sp. Electromigration of microbial cells reduced the biodiversity of the microbial community in soil following EK remediation. At 200 V m(-1) for 10 days, 36% TPH was removed, with a small population of microbial cells flushed out, demonstrating that EK remediation is effective for the present oil-contaminated soils collected in field. PMID:21052991

  18. Long-Term Monitoring of Post-Aquifer Flushing With Cyclodextrin

    NASA Astrophysics Data System (ADS)

    Blanford, W. J.; Hinrichs, R. M.; Brusseau, M. L.; McCray, J. E.; Boving, T.

    2003-12-01

    Cyclodextrins are benign sugar solutions that have been shown at numerous DoD sites to be effective in removing many different types of organic compounds from aquifers through flushing. Cyclodextrins enhance the solubility of many organic contaminants because the interior cavity of the toroidal shaped molecule has favorable conditions for inclusion of low-polarity compounds. They are also effective for aquifer flushing because the outside of the molecule is highly polar resulting in a high aqueous solubility. Their feasibility as a remedial alternative for many sites is dependent on whether unrecovered cyclodextrin mass left in the aquifer after active remediation leads to adverse results. The potential adverse results could include enhanced potential for spreading of hydrophobic contaminant and complications resulting from biodegradation of large quantities of cyclodextrin altering geochemical conditions. In the summer of 2002, a pilot test was performed at a military base in the Norfolk area of Virginia. Through funding by the Environmental Security Technology Certification Program within the DoD, hydroxyl-propyl-beta-cyclodextrin (HPCD) flushing was evaluated as a remedial technique for a chlorinated solvent contaminated aquifer. At the hazardous waste site there is a trichloroethylene (TCE) and sewage contaminated surficial sand aquifer. During the four months of field activities, tens of thousands of gallons of 20 percent wt./vol. HPCD solution were flushed through the aquifer. During and for 1.5 years after the cessation of flushing activities, the concentration of HPCD, TCE, dissolved oxygen (DO), nitrate, sulfate, and iron were monitored within the aquifer by sampling from the high density of monitoring wells at the site. The results of long-term monitoring have found that HPCD concentration continues to linger above 0.5 percent wt./vol. at the site. But, TCE levels have rebounded only slightly from post-flushing levels. Background dissolved oxygen is low

  19. Efficacy and Tolerability of Conventional Nimesulide Versus Beta-Cyclodextrin Nimesulide in Patients with Pain After Surgical Dental Extraction: A Multicenter, Prospective, Randomized, Double-Blind, Double-Dummy Study☆

    PubMed Central

    Bocanegra, Mildred; Seijas, Alberto; Yibirín, Maria González

    2003-01-01

    Background: Pain following extraction of an impacted third molar is widely used to assess analgesic efficacy, especially that of a single dose of a drug. The analgesic activity of conventional nimesulide (CN) has been documented in a variety of types of acute and chronic pain. Beta-cyclodextrin nimesulide (BN) is a new formulation in which nimesulide is included in a cyclodextrin molecule, which increases its solubility in water and its dilution rate, allowing extended, rapid absorption of the drug. Objective: The aim of this study was to assess the efficacy and tolerability of a single dose of BN compared with CN in patients with pain following extraction of an impacted third molar. Methods: This was a prospective, randomized, double-blind, double-dummy study conducted at 3 dentistry centers in Venezuela. The patients were randomized to 1 of 2 groups. One group received a single dose of BN (400-mg tablet, equivalent to 100 mg of nimesulide); the other group received a single dose of CN (100-mg tablet). Both groups also received a placebo. The efficacy variables were (1) pain intensity (PI), assessed on a visual analog scale (VAS) at the following times: 0, 5, 10, 15, 30, and 45 minutes and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration; (2) time to first measurable difference in PI from baseline (PID) (PID ≥1 cm on the VAS; ie, the beginning of analgesic action); (3) maximum PID (max PID); (4) sum of PIDs in the 12-hour observation period; (5) pain relief (PR), as rated on a 5-point scale; (6) maximum PR; and (7) sum of the PR scores in the 12-hour observation period (ie, total PR). For the tolerability analysis, all adverse events (AEs) were to be recorded, and the investigators were to assess whether each AE was drug related. Results: Seventy-two patients were enrolled in the study. Of these, 62 patients (40 women, 22 men; mean [SD] age, 20.1 [5.9] years) were assessed; 35 were treated with BN and 27 with CN. PI reduction was more rapid and greater

  20. Triethanolamine Stabilization of Methotrexate-β-Cyclodextrin Interactions in Ternary Complexes

    PubMed Central

    Barbosa, Jahamunna A. A.; Zoppi, Ariana; Quevedo, Mario A.; de Melo, Polyanne N.; de Medeiros, Arthur S. A.; Streck, Letícia; de Oliveira, Alice R.; Fernandes-Pedrosa, Matheus F.; Longhi, Marcela R.; da Silva-Júnior, Arnóbio A.

    2014-01-01

    The interaction of methotrexate (MTX) with beta-cyclodextrin (β-CD) in the presence of triethanolamine (TEA) was investigated with the aim to elucidate the mechanism whereby self-assembly cyclodextrin systems work in association with this third component. Solubility diagram studies showed synergic increment of the MTX solubility to be about thirty-fold. Experiments using 2D ROESY and molecular modeling studies revealed the inclusion of aromatic ring III of the drug into β-CD cavity, in which TEA contributes by intensifying MTX interaction with β-CD and stabilizes MTX:β-CD:TEA ternary complex by electrostatic interaction. The maintenance of these interactions in solid phase was also studied in ternary MTX:β-CD:TEA and comparisons were made with freeze dried binary MTX:β-CD and physical mixtures. FTIR studies evidenced that MTX–β-CD interaction remained in solid ternary complexes, which was also supported by thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TG)/first derivative of TG analysis (DTG) and C,N,H elementary analysis) and structural (X-ray diffraction analysis, (XRD)) studies, mainly regarding the increment of drug stability. The efficient in vitro drug dissolution studies successfully demonstrated the contribution of ternary complexes, which highlights the importance of this possible new raw material for further applications in drug delivery systems. PMID:25257529

  1. Triethanolamine stabilization of methotrexate-β-cyclodextrin interactions in ternary complexes.

    PubMed

    Barbosa, Jahamunna A A; Zoppi, Ariana; Quevedo, Mario A; de Melo, Polyanne N; de Medeiros, Arthur S A; Streck, Letícia; de Oliveira, Alice R; Fernandes-Pedrosa, Matheus F; Longhi, Marcela R; da Silva-Júnior, Arnóbio A

    2014-01-01

    The interaction of methotrexate (MTX) with beta-cyclodextrin (β-CD) in the presence of triethanolamine (TEA) was investigated with the aim to elucidate the mechanism whereby self-assembly cyclodextrin systems work in association with this third component. Solubility diagram studies showed synergic increment of the MTX solubility to be about thirty-fold. Experiments using 2D ROESY and molecular modeling studies revealed the inclusion of aromatic ring III of the drug into β-CD cavity, in which TEA contributes by intensifying MTX interaction with β-CD and stabilizes MTX:β-CD:TEA ternary complex by electrostatic interaction. The maintenance of these interactions in solid phase was also studied in ternary MTX:β-CD:TEA and comparisons were made with freeze dried binary MTX:β-CD and physical mixtures. FTIR studies evidenced that MTX-β-CD interaction remained in solid ternary complexes, which was also supported by thermal (differential scanning calorimetry (DSC), thermogravimetric analysis (TG)/first derivative of TG analysis (DTG) and C,N,H elementary analysis) and structural (X-ray diffraction analysis, (XRD)) studies, mainly regarding the increment of drug stability. The efficient in vitro drug dissolution studies successfully demonstrated the contribution of ternary complexes, which highlights the importance of this possible new raw material for further applications in drug delivery systems. PMID:25257529

  2. Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques.

    PubMed

    Kalaiselvan, R; Mohanta, G P; Madhusudan, S; Manna, P K; Manavalan, R

    2007-08-01

    The objective of this study was to improve the oral bioavailability and therapeutic efficacy of albendazole (ABZ) employing solid dispersion and cyclodextrin complexation techniques. Solid dispersion (dispersion) was prepared using ABZ and polyvinylpyrrolidone (PVP) polymer (1:1 weight ratio). Ternary inclusion complex (ternary complex) was prepared using ABZ, hydroxypropyl beta-cyclodextrin (HPbetaCD) and L-tartaric acid (1:1:1 molar ratio). In rabbits with high gastric acidity (gastric pH approximately 1), ternary complex and solid dispersion showed a bioavailability enhancement of 3.2 and 2.4 fold respectively, compared to a commercial suspension (p < 0.05). The rise in gastric pH (pH > 5) caused a 62% reduction in AUC (area under the plasma level curve) for the commercial suspension, whereas the reduction in case of PVP dispersion and ternary complex was only 43% and 37% respectively. The rapid absorption of the drug from solid dispersion and ternary complex was reflected in improved anthelmintic efficacy against the systemic phases of Trichinella spiralis. The ternary complex was significantly more efficient than solid dispersion and exhibited the highest larvicidal activity (90%) at a dose of 50 mg x kg(-1) (p < 0.05). These results suggest that the bioavailability and therapeutic efficacy of the ternary complex might be high even if there is a great variation in the gastric pH. PMID:17867556

  3. Synthesis of Phenyl-Adducted Cyclodextrin through the Click Reaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new derivative of ß-cyclodextrin (CD) has been made incorporating the phenyl group through the use of click reaction. The resulting product exhibits a self-association phenomenon through the formation of inclusion compound between the phenyl group and CD. The product has been characterized by 1H...

  4. A closer look at cyclodextrins in mycotoxin analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyclodextrins have seen increased use as components in analytical methods to detect and quantitate a broad range of low molecular weight molecules. Improved detection is frequently associated with inclusion complex formation, and, in some cases, modulation of spectroscopic properties. These cyclic...

  5. New asymmetrical per-substituted cyclodextrins (2-O-methyl-3-O-ethyl- and 2-O-ethyl-3-O-methyl-6-O-t-butyldimethylsilyl-beta-derivatives) as chiral selectors for enantioselective gas chromatography in the flavour and fragrance field.

    PubMed

    Bicchi, Carlo; Cagliero, Cecilia; Liberto, Erica; Sgorbini, Barbara; Martina, Katia; Cravotto, Giancarlo; Rubiolo, Patrizia

    2010-02-12

    Asymmetrically substituted 6(I-VII)-O-t-butyldimethylsilyl(TBDMS)-3(I-VII)-O-ethyl-2(I-VII)-O-methyl-beta-cyclodextrin (MeEt-CD) and 6(I-VII)-O-TBDMS-2(I-VII)-O-ethyl-3(I-VII)-O-methyl-beta-cyclodextrin (EtMe-CD) were synthesised to evaluate the role of the substitution pattern in positions 2 and 3 on the enantioselectivity, in particular in view of their application to routine analysis in fast enantioselective gas chromatography (Es-GC). The chromatographic properties and enantioselectivities of the new derivatives were tested by separating the enantiomers of a series of medium-to-high volatility racemates in the flavour and fragrance field, and compared to those of the corresponding symmetrically substituted 6(I-VII)-O-TBDMS-2(I-VII),3(I-VII)-O-methyl-beta-CD (MeMe-CD) and 6(I-VII)-O-TBDMS-2(I-VII),3(I-VII)-O-ethyl-beta-CD (EtEt-CD), and were then applied to analysis of real-world essential oil (e.o.) samples. A new synthetic process including the sonochemical approach to obtain synthetic reproducibility and significant yields of the per-substituted derivatives with acceptable reaction times was developed. The results show that asymmetrically substituted methyl/ethyl CDs compared to the methyl or ethyl symmetrical derivatives in general provide better enantioselectivity in terms of both enantiomer resolution and number of separated chiral compounds, and show how the substitution pattern in positions 2 and 3 of the CD ring can influence the separation. Moreover, these new CD derivatives with better enantioselectivity are also shown to be very useful in routine analysis for the exhaustive control of samples containing several chiral characterizing markers in a single run. PMID:19846102

  6. Development of Orodispersible Tablets of Candesartan Cilexetil- β -cyclodextrin Complex.

    PubMed

    Sravya, Maddukuri; Deveswaran, Rajamanickam; Bharath, Srinivasan; Basavaraj, Basappa Veerbadraiah; Madhavan, Varadharajan

    2013-01-01

    The aim of this study was to investigate the use of inclusion complexation technique employing β-cyclodextrin in improving the dissolution profile of candesartan cilexetil, a BCS class-II drug, and to formulate the inclusion complex into orodispersible tablets. The inclusion complexes were formed by physical mixing, kneading, coevaporation, and lyophilisation methods. Inclusion complexes were characterized by FTIR, DSC, XRD, NMR, and mass spectral studies. Inclusion complexes prepared using kneading, and lyophilisation techniques in the molar ratio 1 : 5 with β-cyclodextrin were used for formulating orodispersible tablets by direct compression with different superdisintegrants like croscarmellose sodium, crospovidone, sodium starch glycolate, and low substituted hydroxypropyl cellulose in varying concentrations. The directly compressible powder was evaluated for precompression parameters, and the prepared orodispersible tablets were evaluated for postcompression parameters. Drug-excipient compatibility studies showed no interaction, and characterization proved the formation of inclusion complex. In vitro disintegration time was found to be within 3 minutes, and all the formulations showed complete drug release of 100% within 20 minutes. The optimized formulation was found to be stable after 6 months and showed no significant change in drug content. This work proved β-cyclodextrins to be effective solubilizing agent in improving the solubility of poorly water soluble drugs. PMID:26555987

  7. Lanthanide-cyclodextrin complexes as probes for elucidating optical purity by NMR spectroscopy

    SciTech Connect

    Wenzel, T.J.; Bogyo, M.S.; Lebeau, E.L. )

    1994-06-01

    A multidentate ligand is bonded to cyclodextrins by the reaction of diethylenetriaminepentaacetic dianhydride with 6-mono- and 2-mono(ethylenediamine) derivatives of cyclodextrin. Adding Dy(III) to the cyclodextrin derivatives enhances the enantiomeric resolution in the [sup 1]H NMR spectra of carbionoxamine maleate, doxylamine succinate, pheniramine maleate, propranolol hydrochloride, and tryptophan. The enhancement is more pronounced with the secondary derivative. The Dy(III)-induced shifts can be used to elucidate the geometry of cyclodextrin-substrate inclusion complexes. Lanthanide-induced shifts are reported for complexes of aspartame, tryptophan, propranolol, and 1-anilino-8-naphthalenesulfonate with cyclodextrins, and the relative magnitudes of the shifts agree with previously reported structures of the complexes. 37 refs., 9 figs., 5 tabs.

  8. Production of cyclodextrins by CGTase from Bacillus clausii using different starches as substrates.

    PubMed

    Alves-Prado, H F; Carneiro, A A J; Pavezzi, F C; Gomes, E; Boscolo, M; Franco, C M L; da Silva, R

    2008-03-01

    Cyclodextrins (CDs) are cyclic oligasaccharides composed by D-glucose monomers joined by alpha-1,4-D glicosidic linkages. The main types of CDs are alpha-, beta- and gamma-CDs consisting of cycles of six, seven, and eight glucose monomers, respectively. Their ability to form inclusion complexes is the most important characteristic, allowing their wide industrial application. The physical property of the CD-complexed compound can be altered to improve stability, volatility, solubility, or bio-availability. The cyclomaltodextrin glucanotransferase (CGTase, EC 2.4.1.19) is an enzyme capable of converting starch into CD molecules. In this work, the CGTase produced by Bacillus clausii strain E16 was used to produce CD from maltodextrin and different starches (commercial soluble starch, corn, cassava, sweet potato, and waxy corn starches) as substrates. It was observed that the substrate sources influence the kind of CD obtained and that this CGTase displays a beta-CGTase action, presenting a better conversion of soluble starch at 1.0%, of which 80% was converted in CDs. The ratio of total CD produced was 0:0.89:0.11 for alpha/beta/gamma. It was also observed that root and tuber starches were more accessible to CGTase action than seed starch under the studied conditions. PMID:18421582

  9. Complexation study and anticellular activity enhancement by doxorubicin-cyclodextrin complexes on a multidrug-resistant adenocarcinoma cell line.

    PubMed

    Al-Omar, A; Abdou, S; De Robertis, L; Marsura, A; Finance, C

    1999-04-19

    Ability of molecular complexes of [Doxorubicin (DX)-cyclodextrin (Cd)] to enhance the anticellular activity of antineoplastic drug Doxorubicin and to reverse its multidrug resistance has been investigated. A spectroscopic study of the alpha, beta, and gamma-[DX-Cds] complexes has been investigated in relation to their biological effects on a multidrug resistant (MDR) human rectal adenocarcinoma cell line (HRT-18). A ten fold enhancement of DX anticellular activity in presence of beta-cyclodextrin alone was detected. PMID:10328296

  10. Host-Guest Inclusion Complexes between Amlodipine Enantiomers in the Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation by using their Enantioselective Extraction

    PubMed Central

    Al Azzam, Khaldun M.; Abdallah, Hassan H.; Halim, Hairul N. Abdul; Ahmad, Maizatul Akmam; Shaibah, Hassan

    2015-01-01

    The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-β-CD has the strongest recognition ability among the three β-CD derivatives studied, namely HP-β-CD, hydroxyethyl-β-cyclodextrin (HE-β-CD), and methylated-β-cyclodextrin (Me-β-CD), due to the large interaction energies (Ecomp = −14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = −5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems. PMID:26839848

  11. Host-Guest Inclusion Complexes between Amlodipine Enantiomers in the Biphasic Recognition Chiral Extraction System using Tartaric Acid and β-Cyclodextrin Derivatives as Positive Confirmation by using their Enantioselective Extraction.

    PubMed

    Al Azzam, Khaldun M; Abdallah, Hassan H; Halim, Hairul N Abdul; Ahmad, Maizatul Akmam; Shaibah, Hassan

    2015-01-01

    The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S-enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-β-CD has the strongest recognition ability among the three β-CD derivatives studied, namely HP-β-CD, hydroxyethyl-β-cyclodextrin (HE-β-CD), and methylated-β-cyclodextrin (Me-β-CD), due to the large interaction energies (Ecomp = -14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = -5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems. PMID:26839848

  12. [The preparation, characterization and ultraviolet photodegradation of LNG-HP-beta-CD].

    PubMed

    Wang, Da-wei; Liu, Qi; Liu, Ming; Liu, Xiao-hui

    2011-03-01

    The characteristics of levonorgestrel (LNG), low solubility and the quick degradation under ultraviolet, limited its study and application in rodent contraception. The inclusion complex of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with LNG was investigated in present study. The inclusion complex was prepared by solution method and characterized by ultraviolet absorption spectrum and infrared spectrum spectra. And the stability was evaluated by being exposed to ultraviolet. The authors' results showed that the accurate and simple method of quantitative determination for LNG was established by ultraviolet spectrum, the molar ratio of the complex was 1:1 calculated from the phase solubility diagram, the stability constant was 187.3 L x mol(-1) at 25 degrees C, and the formation of the inclusion complex was validated by UV-Vis and Fourier transform infrared spectroscopy. Moreover, the degradation rate of the inclusion complex was less than 5%, which was slower than the LNG monomer. The present study indicated that HP-beta-CD could be formed inclusion complexes with LNG and the solubility, and stability were obviously enhanced. PMID:21595245

  13. Synthesis of polyrotaxanes from acetyl-β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Ristić, I. S.; Nikolić, L.; Nikolić, V.; Ilić, D.; Budinski-Simendić, J.

    2011-12-01

    Polyrotaxanes are intermediary products in the synthesis of topological gels. They are created by inclusion complex formation of hydrophobic linear macromolecules with cyclodextrins or their derivatives. Then, pairs of cyclodextrin molecules with covalently linkage were practically forming the nodes of the semi-flexible polymer network. Such gels are called topological gels and they can absorb huge quantities of water due to the net flexibility allowing the poly(ethylene oxide) chains to slide through the cyclodextrin cavities, without being pulled out altogether. For polyrotaxane formation poly(ethylene oxide) was used like linear macromolecules. There are hydroxyl groups at poly(ethylene oxide) chains, whereby the linking of the voluminous molecules should be made. To avoid the reaction of cyclodextrin OH groups with stoppers, they should be protected by, e.g., acetylation. In this work, the acetylation of the OH groups of β-cyclodextrin was performed by acetic acid anhydride with iodine as the catalyst. The acetylation reaction was assessed by the FTIR and HPLC method. By the HPLC analysis was found that the acetylation was completed in 20 minutes. Inserting of poly(ethylene oxide) with 4000 g/mol molecule mass into acetyl-β-cyclodextrin with 2:1 poly(ethylene oxide) monomer unit to acetyl-β-cyclodextrin ratio was also monitored by FTIR, and it was found that the process was completed in 12 h at the temperature of 10°C. If the process is performed at temperatures above 10°C, or for periods longer than 12 hours, the process of uncontrolled hydrolysis of acetate groups was initiated.

  14. Formation of β-cyclodextrin complexes in an anhydrous environment.

    PubMed

    Sifaoui, Hocine; Modarressi, Ali; Magri, Pierre; Stachowicz-Kuśnierz, Anna; Korchowiec, Jacek; Rogalski, Marek

    2016-09-01

    The formation of inclusion complexes of β-cyclodextrin was studied at the melting temperature of guest compounds by differential scanning calorimetry. The complexes of long-chain n-alkanes, polyaromatics, and organic acids were investigated by calorimetry and IR spectroscopy. The complexation ratio of β-cyclodextrin was compared with results obtained in an aqueous environment. The stability and structure of inclusion complexes with various stoichiometries were estimated by quantum chemistry and molecular dynamics calculations. Comparison of experimental and theoretical results confirmed the possible formation of multiple inclusion complexes with guest molecules capable of forming hydrogen bonds. This finding gives new insight into the mechanism of formation of host-guest complexes and shows that hydrophobic interactions play a secondary role in this case. Graphical abstract The formation of complexes of β-cyclodextrin with selected n-alkanes, polyaromatics, and organic acids in an anhydrous environment is studied by differential scanning calorimetry, IR spectroscopy, and molecular modeling. The results obtained confirm the possible formation of multiple inclusion complexes with guest molecules capable of forming hydrogen bonds and give a new perspective on the mechanism of formation of host-guest complexes. PMID:27518085

  15. EFFECT OF B-CYCLODEXTRIN ON MUCOCHLORIC ACID AND 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE

    EPA Science Inventory

    Using a combination of IR and UV techniques, evidence is presented for inclusion complex formation between mucochloric acid and B-cyclodextrin in acidic aqueous solutions. V evidence supports the conclusion that under these acidic conditions mucochloric acid-B-cyclodextrin comple...

  16. Ternary cyclodextrin polyurethanes containing phosphate groups: Synthesis and complexation of ciprofloxacin.

    PubMed

    Moreira, Mirna Pereira; Andrade, George Ricardo Santana; de Araujo, Marcia Valeria Gaspar; Kubota, Tatiana; Gimenez, Iara F

    2016-10-20

    Synthesis of ternary polyurethanes (PUs) from hexamethylenediisocyanate, β-cyclodextrin and β-glycerophosphate (acid and calcium salt) was studies varying synthesis parameters such as monomer proportion, heating method (reflux and microwave), and catalyst amount. Favorable conditions were provided by microwave irradiation and use of β-glycerophosphoric acid although the results suggest that it is possible to obtain ternary PUs with the calcium salt. FTIR data indicated the existence of secondary urea linkages. After characterization of ternary PUs by FTIR spectroscopy, XRD and thermal analysis, as well as evidences that the cyclodextrin cavities remained active toward inclusion of guest molecules, the possibility of inclusion of the antibiotic ciprofloxacin was evaluated. Absence of ciprofloxacin melting peak in DSC curves indicated that it is molecularly dispersed within the polymer, possibly included in the cyclodextrin. In vitro release experiments suggested additional non-inclusion interactions, showing also that the use of dialysis membranes may mask the actual release profile. PMID:27474600

  17. Complexation of cyclodextrins with flavines in aqueous solutions

    NASA Astrophysics Data System (ADS)

    Terekhova, I. V.

    2014-01-01

    Data on the binding mode and thermodynamics of complex formation for various cyclodextrins (CDs) with flavines are summarized. It is shown that the governing factors of complexation are the size, degree of hydration, and hydrophobicity of the guest molecule. It is found that the presence of small hydrophobic substituents in a flavine's structure increases their affinity toward cyclodextrin cavities, raising the stability of a complex. In contrast, the presence of bulky and polar side groups in a flavine's structure prevents its inclusion in a macrocyclic cavity and weakens complexation. The size of a CD cavity plays a minor role in the interaction between CDs and flavines, since the inclusion of a guest molecule is only partial.

  18. Fluorescent H-Aggregates Hosted by a Charged Cyclodextrin Cavity.

    PubMed

    Mudliar, Niyati H; Singh, Prabhat K

    2016-05-23

    Most macrocyclic host molecules, including cyclodextrins, usually prevent self-aggregation of the guest organic molecules, by exploiting inclusion complexation of the guest with the host. In this work, it was found that a negatively charged β-cylcodextrin derivative induces aggregation of a well-known amyloid sensing dye, Thioflavin-T, and leads to an unprecedented formation of the rarely observed emissive H-type aggregates of the dye. PMID:27028039

  19. Formation of supramolecular permethrin/β-cyclodextrin nanorods

    NASA Astrophysics Data System (ADS)

    Yang, Guang-Fu; Wang, Hong-Bo; Yang, Wen-Chao; Gao, Daquan; Zhan, Chang-Guo

    2006-09-01

    Molecular dynamics simulations along with scanning tunneling microscopy (STM) imaging demonstrate the formation of a novel type of nanorods, with a stable [permethrin(β-CD)2]n structure in which the host:guest ratio is 2:1 and n =21-27 giving a length of ˜30.0-38.5nm and an average diameter of ˜1.5nm, self-assembled from an inclusion complex composed of permethrin and biocompatible β-cyclodextrin.

  20. Cyclodextrin KnowledgeBase a web-based service managing CD-ligand complexation data.

    PubMed

    Hazai, Eszter; Hazai, Istvan; Demko, Laszlo; Kovacs, Sandor; Malik, David; Akli, Peter; Hari, Peter; Szeman, Julianna; Fenyvesi, Eva; Benes, Edina; Szente, Lajos; Bikadi, Zsolt

    2010-08-01

    Cyclodextrins are cyclic oligosaccharides that are able to form water-soluble inclusion complexes with small molecules. Because of their complexing ability, they are widely applied in food, pharmaceutical and chemical industries. In this paper we describe the development of a free web-service, Cyclodextrin KnowledgeBase: ( http://www.cyclodextrin.net ). The database contains four modules: the Publication, Interaction, Chirality and Analysis Modules. In the Publication Module, almost 50,000 publication details are collected that can be retrieved by text search. In the Interaction and Chirality Modules relevant literature data on cyclodextrin complexation and chiral recognition are collected that can be retrieved by both text and structural searches. Moreover, in the Analysis Module, the geometries of small molecule-cyclodextrin complexes can be predicted using molecular docking tools in order to explore the structures and interaction energies of the inclusion complexes. Complex geometry prediction is made possible by the built-in database of 95 cyclodextrin derivatives, where the 3D structures as well as the partial charges are calculated and stored for further utilization. The use of the database is demonstrated by several examples. PMID:20521083

  1. Cyclodextrins in pharmaceutical formulations II: solubilization, binding constant, and complexation efficiency.

    PubMed

    Jambhekar, Sunil S; Breen, Philip

    2016-02-01

    Cyclodextrins are cyclic oligosaccharides that have been recognized as pharmaceutical adjuvants for the past 20 years. The molecular structure of these glucose derivatives, which approximates a truncated cone, bucket, or torus, generates a hydrophilic exterior surface and a nonpolar interior cavity. Cyclodextrins can interact with appropriately sized drug molecules to yield an inclusion complex. These noncovalent inclusion complexes offer a variety of advantages over noncomplexed forms of a drug. Cyclodextrins are carbohydrates that are primarily used to enhance the aqueous solubility, physical chemical stability, and bioavailability of drugs. Their other applications include preventing drug-drug interactions, converting liquid drugs into microcrystalline powders, minimizing gastrointestinal and ocular irritation, and reducing or eliminating unpleasant taste and smell. Here, we focus on the solubilization of drugs by complexation, and discuss the determination and significance of binding constants for cyclodextrin complexes, and the determination of complexation efficiency and factors that influence it. We also make some general observations on cyclodextrin complexation and the use of cyclodextrins in solid, as well as parenteral, dosage forms. PMID:26687191

  2. Evaluation of newly synthesized and commercially available charged cyclomaltooligosaccharides (cyclodextrins) for capillary electrokinetic chromatography.

    PubMed

    Culha, Mustafa; Schell, Fred M; Fox, Shannon; Green, Thomas; Betts, Thomas; Sepaniak, Michael J

    2004-01-22

    A highly new charged cyclodextrin (CD) derivatives, (6-O-carboxymethyl-2,3-di-O-methyl)cyclomaltoheptaoses (CDM-beta-CDs), was synthesized and characterized as anionic reagents for capillary electrophoresis (CE) in an electrokinetic chromatography mode of separation. Substitution with dimethyl groups at the secondary hydroxyl sites of the CD is aimed at influencing the magnitude and selectivity of analyte-CD interactions, while substitution by carboxymethyl groups at the primary hydroxyl sites provides for high charge and electrophoretic mobility. Full regioselective methylation at the secondary hydroxyl sites was achieved in this work, while substitution at the primary hydroxyl sites generated a mixture of multiply charged products. The separation performance of CDM-beta-CD was evaluated using a variety of analyte mixtures. The results obtained from commercially available negatively charged cyclodextrins, heptakis(2,3-di-O-methyl-6-O-sulfo)cyclomaltoheptaose (HDMS-beta-CD) and O-(carboxymethyl)cyclomaltoheptaose (CM-beta-CD) with an average degree of substitution one (DS 1), were compared to CDM-beta-CD using a sample composed of eight positional isomers of dihydroxynaphthalene. Four hydroxylated polychlorobiphenyl derivatives, a group of chiral and isomeric catchecins, and chiral binaphthyl compounds were also separated with CDM-beta-CD. The effect of adding neutral beta-cyclodextrin (beta-CD) into the running buffer containing charged cyclodextrins was investigated and provided evidence of significant inter-CD interactions. Under certain running buffer conditions, the charged cyclodextrins also appear to adsorb to the capillary walls to various degrees. PMID:14698882

  3. Cyclodextrin-based supramolecular systems for drug delivery: Recent progress and future perspective

    PubMed Central

    Zhang, Jianxiang; Ma, Peter X

    2013-01-01

    The excellent biocompatibility and unique inclusion capability as well as powerful functionalization capacity of cyclodextrins and their derivatives make them especially attractive for engineering novel functional materials for biomedical applications. There has been increasing interest recently to fabricate supramolecular systems for drug and gene delivery based on cyclodextrin materials. This review focuses on state of the art and recent advances in the construction of cyclodextrin-based assemblies and their applications for controlled drug delivery. First, we introduce cyclodextrin materials utilized for self-assembly. The fabrication technologies of supramolecular systems including nanoplatforms and hydrogels as well as their applications in nanomedicine and pharmaceutical sciences are then highlighted. At the end, the future directions of this field are discussed. PMID:23673149

  4. Prednisolone-appended alpha-cyclodextrin: alleviation of systemic adverse effect of prednisolone after intracolonic administration in 2,4,6-trinitrobenzenesulfonic acid-induced colitis rats.

    PubMed

    Yano, H; Hirayama, F; Arima, H; Uekama, K

    2001-12-01

    The titled compound is a cyclodextrin derivative in which prednisolone 21-succinate (PDsuc) is covalently bound to one of the secondary hydroxyl groups of alpha-cyclodextrin (alpha-CyD) via an ester linkage. In this study, the PDsuc-appended alpha-CyD ester conjugate (PDsuc/alpha-CyD conjugate) was intracolonically administered to rats with 2,4,6-trinitrobenzensulfonic acid-induced colitis, and its antiinflammatory and systemic adverse effects were compared with those of prednisolone (PD) alone and the PD/2-hydroxypropyl-beta-CyD complex (PD/HP-beta-CyD complex), which is a noncovalent inclusion complex. Colonic damage score, ratio of distal colon wet weight to body weight, and myeloperoxidase activity were evaluated as measures of the therapeutic effect of PD, whereas the ratio of thymus wet weight to body weight was evaluated as a measure of the side effect of PD. The local antiinflammatory activity increased in the order of PD alone approximately PDsuc/alpha-CyD conjugate < PD/HP-beta-CyD complex. As to systemic adverse effect, the PD/HP-beta-CyD complex and PD alone caused thymolysis at doses of 5-10 mg/kg. In contrast, the PDsuc/alpha-CyD conjugate showed no clear systemic adverse effect at the same doses. The low adverse effect of the conjugate may be ascribed to the slow release of PD in the colon, which keeps the local concentration in the colon at a low but constant level. The results suggest that the PDsuc/alpha-CyD conjugate can alleviate the systemic adverse effect of PD while maintaining the therapeutic activity of PD. This kind of knowledge will be useful in the rational design of steroid prodrugs for the colon-specific drug delivery system. PMID:11745769

  5. Effect of the complexation with cyclodextrins on the in vitro antiviral activity of ganciclovir against human cytomegalovirus.

    PubMed

    Nicolazzi, C; Abdou, S; Collomb, J; Marsura, A; Finance, C

    2001-02-01

    The toxicity of the molecules currently used in the treatment of human cytomegalovirus (HCMV) in immunocompromised hosts often causes interruption of the therapy. Cyclodextrins (Cds), oligosaccharides possessing a hydrophobic cavity, have the property of forming inclusion complexes with a great number of molecules, improving their bioavailability and their biological properties. In this study, we have tested the ability of three native Cds to improve the antiviral effect of ganciclovir (GCV) on two HCMV strains: AD169, a reference susceptible strain, and RC11, a GCV resistant strain. The efficacy of the GCV, expressed in IC50 values, showed no improvement in the presence of alpha-Cd, while the use of beta- and gamma-Cd improved by 6- and 4-fold, respectively, its antiviral activity tested on AD169 strain. The influence of beta- or gamma-Cd on GCV efficiency evaluated on RC11 strain showed a decrease of the IC50. Parallel NMR studies were undertaken in order to characterize formation of [GCV:Cd] complexes. The results showed that complexation between alpha- or gamma-Cd and GCV did not occur. In contrast, spectra proved that beta-Cd formed an inclusion complex with GCV. This complex was characterized in UV-Visible spectrophotometry and the influence of the beta-Cd on the GCV penetration in cells was measured. The use of Cds as carriers of antiviral drugs would be a good alternative to traditional treatment, because it may allow the administration of lower doses and so continuous treatment by reducing the toxic effects of drugs. PMID:11249120

  6. Analytical techniques for characterization of cyclodextrin complexes in aqueous solution: a review.

    PubMed

    Mura, Paola

    2014-12-01

    Cyclodextrins are cyclic oligosaccharides endowed with a hydrophilic outer surface and a hydrophobic inner cavity, able to form inclusion complexes with a wide variety of guest molecules, positively affecting their physicochemical properties. In particular, in the pharmaceutical field, cyclodextrin complexation is mainly used to increase the aqueous solubility and dissolution rate of poorly soluble drugs, and to enhance their bioavailability and stability. Analytical characterization of host-guest interactions is of fundamental importance for fully exploiting the potential benefits of complexation, helping in selection of the most appropriate cyclodextrin. The assessment of the actual formation of a drug-cyclodextrin inclusion complex and its full characterization is not a simple task and often requires the use of different analytical methods, whose results have to be combined and examined together. The purpose of the present review is to give, as much as possible, a general overview of the main analytical tools which can be employed for the characterization of drug-cyclodextrin inclusion complexes in solution, with emphasis on their respective potential merits, disadvantages and limits. Further, the applicability of each examined technique is illustrated and discussed by specific examples from literature. PMID:24680374

  7. Instantaneous inclusion of a polynucleotide and hydrophobic guest molecules into a helical core of cationic beta-1,3-glucan polysaccharide.

    PubMed

    Ikeda, Masato; Hasegawa, Teruaki; Numata, Munenori; Sugikawa, Kouta; Sakurai, Kazuo; Fujiki, Michiya; Shinkai, Seiji

    2007-04-01

    We succeeded in the quantitative and selective introduction of an ammonium cationic group into the C6 position of Curdlan (CUR) by "Click Chemistry", and the obtained cationic Curdlan (CUR-N+) showed good solubility in water. ORD studies suggested that CUR-N+ adopts a single-stranded structure, different from a right-handed, triple-stranded helical structure of beta-1,3-glucan polysaccharides in water. It has been revealed that the polymeric complexes of CUR-N+ with polymeric guest molecules, such as polycytidylic acid (poly(C)), permethyldecasilane (PMDS), and single-walled carbon nanotubes (SWNTs), can be easily obtained by just mixing them in water with sonication. The characterization of the resultant CUR-N+-poly(C) complexes by UV-vis, CD spectroscopic measurements, and AFM and TEM observations revealed that they have stoichiometric, nanosized fibrous structures. From these experimental results as well as our precedent studies (e.g., refs 6 and 23), we propose that the complexation would be driven by the cooperative action of (1) the hydrogen-bonding interaction between the OH group at the C2 position and hydrogen-bonding sites of the cytosine ring (ref 6d), (2) the electrostatic interaction between the ammonium cation and the phosphate anion (ref 23), as well as (3) the background hydrophobic interaction. In addition, the complexed polynucleotide chain showed a strong resistance against enzymatic hydrolysis. Likewise, the dispersion of PMDS and SWNTs in water by CUR-N+ and the fibrous structures of the complexes were confirmed by spectroscopic measurements as well as microscopic observations. These binding properties of CUR-N+, which can proceed spontaneously in water, clearly differ from those of schizophyllan (SPG), which inevitably require a denature-renature process corresponding to a conversion of a triple strand to single strands induced by DMSO or base for inclusion of polymeric guest molecules. PMID:17352476

  8. Complexation of estragole as pure compound and as main component of basil and tarragon essential oils with cyclodextrins.

    PubMed

    Kfoury, Miriana; Auezova, Lizette; Ruellan, Steven; Greige-Gerges, Hélène; Fourmentin, Sophie

    2015-03-15

    Inclusion complexes of estragole (ES) as pure compound and as main component of basil and tarragon essential oils (EOs) with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RAMEB), a low methylated-β-cyclodextrin (CRYSMEB) and γ-cyclodextrin (γ-CD) were characterized. Formation constants (Kf) of the complexes were determined in aqueous solution by nonlinear regression analysis using static headspace gas chromatography (SH-GC) and UV-visible spectroscopy. Solid inclusion complexes were prepared by the freeze-drying method for different CD:ES molar ratios and were characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). Inclusion complexes formation allowed the controlled release of ES. Moreover, increased DPPH radical scavenging activity and photostability of ES and ES containing EOs (ESEOs) were observed in the presence of CDs. These findings suggest that encapsulation with CDs could be an efficient tool to improve the use of ES and ESEOs in aromatherapy, cosmetic and food fields. PMID:25542121

  9. Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions.

    PubMed

    Rizzi, Vito; Matera, Sergio; Semeraro, Paola; Fini, Paola; Cosma, Pinalysa

    2016-01-01

    Since several years the inclusion of organic compounds (guests) within the hydrophobic cavity (host) of cyclodextrins (CDs) has been the subject of many investigations. Interestingly, the formation of inclusion complexes could affect the properties of the guest molecules and, for example, the influence of the delivery system can be a method to improve/change the photochemical behavior of the guest. In particular, very recent studies have shown the protective role of CDs preventing the degradation of the encapsulated guest. Starting from this consideration, in this work, only the structure and complexation mode of the inclusion complexes involving 4-thiothymidine (S(4)TdR, a known photosensitizer) and five CDs, namely 2-hydroxypropyl-α-cyclodextrin (2-HP-α-CD), 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (2-HP-γ-CD), heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB CD) and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB CD) were investigated by different spectroscopic techniques (UV-vis, FTIR-ATR, (1)H NMR) and cyclic voltammetry analysis (CV). This work is necessary for a prospective research on the photoreactivity of S(4)TdR in aqueous environment and in the presence of CDs to prevent its degradation under irradiation. UV-vis, FTIR-ATR and CV measurements suggested the formation of supramolecular structures involving the employed CDs and mainly the pyrimidine ring of S(4)TdR. (1)H NMR analyses confirmed such indication, unveiling the presence of inclusion complexes. The strongest and deepest interactions were suggested when TRIMEB and DIMEB CDs were studied. The S(4)TdR affinity towards CDs was also evaluated by using the Benesi-Hildebrand (B-H) equation at 25 °C employing CV and (1)H NMR methods. The stoichiometry of the interaction was also inferred and it appears to be 1:1 for all examined CDs. PMID:27340447

  10. Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

    PubMed Central

    Rizzi, Vito; Matera, Sergio; Semeraro, Paola; Fini, Paola

    2016-01-01

    Summary Since several years the inclusion of organic compounds (guests) within the hydrophobic cavity (host) of cyclodextrins (CDs) has been the subject of many investigations. Interestingly, the formation of inclusion complexes could affect the properties of the guest molecules and, for example, the influence of the delivery system can be a method to improve/change the photochemical behavior of the guest. In particular, very recent studies have shown the protective role of CDs preventing the degradation of the encapsulated guest. Starting from this consideration, in this work, only the structure and complexation mode of the inclusion complexes involving 4-thiothymidine (S4TdR, a known photosensitizer) and five CDs, namely 2-hydroxypropyl-α-cyclodextrin (2-HP-α-CD), 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD), 2-hydroxypropyl-γ-cyclodextrin (2-HP-γ-CD), heptakis-(2,6-di-O-methyl)-β-cyclodextrin (DIMEB CD) and heptakis-(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB CD) were investigated by different spectroscopic techniques (UV–vis, FTIR–ATR, 1H NMR) and cyclic voltammetry analysis (CV). This work is necessary for a prospective research on the photoreactivity of S4TdR in aqueous environment and in the presence of CDs to prevent its degradation under irradiation. UV–vis, FTIR–ATR and CV measurements suggested the formation of supramolecular structures involving the employed CDs and mainly the pyrimidine ring of S4TdR. 1H NMR analyses confirmed such indication, unveiling the presence of inclusion complexes. The strongest and deepest interactions were suggested when TRIMEB and DIMEB CDs were studied. The S4TdR affinity towards CDs was also evaluated by using the Benesi–Hildebrand (B–H) equation at 25 °C employing CV and 1H NMR methods. The stoichiometry of the interaction was also inferred and it appears to be 1:1 for all examined CDs. PMID:27340447

  11. From algal polysaccharides to cyclodextrins to stabilize a urease inhibitor.

    PubMed

    Pro, Danièle; Huguet, Samuel; Arkoun, Mustapha; Nugier-Chauvin, Caroline; Garcia-Mina, José Maria; Ourry, Alain; Wolbert, Dominique; Yvin, Jean-Claude; Ferrières, Vincent

    2014-11-01

    N-Butyl-phosphorotriamide (NBPT) is a fertilizer widely used for its urease inhibiting properties. Nevertheless, formulations currently commercialized are complex and do not avoid severe decrease of activity due to the low stability of the bioactive compound under acidic conditions. According to its structure, NPBT was thought to be able to interact with both polar additives, by its phosphoramide function, and hydrophobic ones, through its alkyl chain. In this context, and in order to simplify formulations of this bioactive compound, a panel of natural polysaccharides was studied, including starch, β-(1,3)-glucans, carraghenans and alginates. We also used cyclodextrins, characterized the most stable inclusion complex with α-cyclodextrin and evaluated the stability of NBPT thus protected against hydrolysis under acidic conditions. PMID:25129728

  12. Micrometer size rod formed by secondary self assembly of omeprazole with α- and β-cyclodextrins.

    PubMed

    Rajendiran, N; Venkatesh, G

    2015-02-25

    Self assembly of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) micro rods induced by omeprazole (OMP) were observed by SEM and TEM. OMP/CD inclusion complexes have formed the secondary self assembly micro meter size rod like structure. This structure was driven by the intermolecular hydrogen bonding as well as van der Waals forces. Both forces induced the ordered assembly and arrangement of OMP/CD inclusion complexes, whereas CD molecules acted as molecular bricks. The OMP/CD inclusion complexes primary assembled form individual nanorods and then secondary self aggregate nanorods were form a micro meter rod structure. The results indicate that inter-nanotubular hydrogen bonding plays a crucial role in the formation of the self assembled micro rods. The inclusion complexes were also characterized using FT-IR, DSC, powder XRD, (1)H NMR, absorption, fluorescence, life time measurements and molecular modeling methods. PMID:25277631

  13. Micrometer size rod formed by secondary self assembly of omeprazole with α- and β-cyclodextrins

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Venkatesh, G.

    2015-02-01

    Self assembly of α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) micro rods induced by omeprazole (OMP) were observed by SEM and TEM. OMP/CD inclusion complexes have formed the secondary self assembly micro meter size rod like structure. This structure was driven by the intermolecular hydrogen bonding as well as van der Waals forces. Both forces induced the ordered assembly and arrangement of OMP/CD inclusion complexes, whereas CD molecules acted as molecular bricks. The OMP/CD inclusion complexes primary assembled form individual nanorods and then secondary self aggregate nanorods were form a micro meter rod structure. The results indicate that inter-nanotubular hydrogen bonding plays a crucial role in the formation of the self assembled micro rods. The inclusion complexes were also characterized using FT-IR, DSC, powder XRD, 1H NMR, absorption, fluorescence, life time measurements and molecular modeling methods.

  14. Synergistic radical scavenging potency of curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes.

    PubMed

    Aadinath, W; Bhushani, Anu; Anandharamakrishnan, C

    2016-07-01

    Curcumin is a highly potent nutraceutical associated with various health benefits. However, its hydrophobic nature affects its bioavailability and bioactivity, and limits nutraceutical applications. Drug-in-cyclodextrin-in-liposome has the ability to mask the hydrophobic nature of drug and achieve better encapsulation. Also, encapsulating iron oxide nanoparticles (IONPs) within liposomes endow additional beneficial functionalities of IONPs. In the present study, curcumin-β-cyclodextrin inclusion complex (IC) and IONPs were co-encapsulated within liposomes (curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes) to achieve the synergistic antioxidant potential of curcumin and IONPs. IC of curcumin-β-cyclodextrin was prepared by a simple rapid method and successful inclusion was confirmed by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). Mean diameter of IONPs was found to be 180nm and X-ray diffraction pattern confirmed the formation of hematite nanoparticles. Band gap energy calculated using absorption spectra was 2.25eV, which falls in close proximity with the theoretically calculated values of hematite. Mean diameter of curcumin-in-β-cyclodextrin-in-nanomagnetoliposomes was 67nm and encapsulation efficiency of curcumin was found to be 71%. Further, the co-encapsulated particles possessed significantly low IC50 value (64.7791μg/ml, p<0.01) compared to conventional curcumin liposome and IONPs, indicating its synergistically enhanced radical scavenging property. PMID:27127056

  15. Cyclodextrins in pharmaceutical formulations I: structure and physicochemical properties, formation of complexes, and types of complex.

    PubMed

    Jambhekar, Sunil S; Breen, Philip

    2016-02-01

    Cyclodextrins are cyclic oligosaccharides that have been recognized as pharmaceutical adjuvants for the past 20 years. The molecular structure of these glucose derivatives, which approximates a truncated cone, bucket, or torus, generates a hydrophilic exterior surface and a nonpolar interior cavity. Cyclodextrins can interact with appropriately sized drug molecules to yield an inclusion complex. These noncovalent inclusion complexes offer a variety of advantages over the noncomplexed form of a drug. Cyclodextrins are primarily used to enhance the aqueous solubility, physical chemical stability, and bioavailability of drugs. Their other applications include preventing drug-drug interactions, converting liquid drugs into microcrystalline powders, minimizing gastrointestinal and ocular irritation, and reducing or eliminating unpleasant taste and smell. Here, we discuss the physical chemical properties of various cyclodextrins, including the effects of substitutions on these properties. Additionally, we report on the regulatory status of their use, commercial products containing cyclodextrins, toxicological considerations, and the forces involved in complex formation. We also highlight the types of complex formed and discuss the methods used to determine the types of complex present. PMID:26686054

  16. Cyclodextrin-grafted electrospun cellulose acetate nanofibers via “Click” reaction for removal of phenanthrene

    NASA Astrophysics Data System (ADS)

    Celebioglu, Asli; Demirci, Serkan; Uyar, Tamer

    2014-06-01

    Beta-cyclodextrin (β-CD) functionalized cellulose acetate (CA) nanofibers have been successfully prepared by combining electrospinning and “click” reaction. Initially, β-CD and electrospun CA nanofibers were modified so as to be azide-β-CD and propargyl-terminated CA nanofibers, respectively. Then, “click” reaction was performed between modified CD molecules and CA nanofibers to obtain permanent grafting of CDs onto nanofibers surface. It was observed from the SEM image that, while CA nanofibers have smooth surface, there were some irregularities and roughness at nanofibers morphology after the modification. Yet, the fibrous structure was still protected. ATR-FTIR and XPS revealed that, CD molecules were successfully grafted onto surface of CA nanofibers. The adsorption capacity of β-CD-functionalized CA (CA-CD) nanofibers was also determined by removing phenanthrene (polycyclic aromatic hydrocarbons, PAH) from its aqueous solution. Our results indicate that CA-CD nanofibers have potential to be used as molecular filters for the purpose of water purification and waste water treatment by integrating the high surface area of nanofibers with inclusion complexation property of CD molecules.

  17. Modeling the effects of cyclodextrin on intracellular membrane vesicles from Cos-7 cells prepared by sonication and carbonate treatment

    PubMed Central

    Kilbride, Peter; Woodward, Holly J.; Tan, Kuan Boone; Thanh, Nguyễn T.K.; Chu, K.M. Emily; Minogue, Shane

    2015-01-01

    Cholesterol has important functions in the organization of membrane structure and this may be mediated via the formation of cholesterol-rich, liquid-ordered membrane microdomains often referred to as lipid rafts. Methyl-beta-cyclodextrin (cyclodextrin) is commonly used in cell biology studies to extract cholesterol and therefore disrupt lipid rafts. However, in this study we reassessed this experimental strategy and investigated the effects of cyclodextrin on the physical properties of sonicated and carbonate-treated intracellular membrane vesicles isolated from Cos-7 fibroblasts. We treated these membranes, which mainly originate from the trans-Golgi network and endosomes, with cyclodextrin and measured the effects on their equilibrium buoyant density, protein content, represented by the palmitoylated protein phosphatidylinositol 4-kinase type IIα, and cholesterol. Despite the reduction in mass stemming from cholesterol removal, the vesicles became denser, indicating a possible large volumetric decrease, and this was confirmed by measurements of hydrodynamic vesicle size. Subsequent mathematical analyses demonstrated that only half of this change in membrane size was attributable to cholesterol loss. Hence, the non-selective desorption properties of cyclodextrin are also involved in membrane size and density changes. These findings may have implications for preceding studies that interpreted cyclodextrin-induced changes to membrane biochemistry in the context of lipid raft disruption without taking into account our finding that cyclodextrin treatment also reduces membrane size. PMID:26528413

  18. [Interactions between cyclodextrins and triglycerides: from emulsion stabilisation to the emergence of a new drug delivery system called "beads"].

    PubMed

    Hamoudi, M; Trichard, L; Grossiord, J-L; Chaminade, P; Duchêne, D; Le Bas, G; Fattal, E; Bochot, A

    2009-11-01

    Natural cyclodextrins are cyclic oligosaccharides which can be modified to obtain more water soluble or insoluble derivatives. The main interest of cyclodextrins results from their ability to form an inclusion complex with hydrophobic molecules. Inclusion constitutes a true molecular encapsulation. This property is employed in pharmaceutical industry to facilitate the formulation of poorly water soluble and/or fragile drugs. A more recent application of cyclodextrins consists in their use in the preparation of dispersed systems such as micro- and nanoparticles or even liposomes. When incorporated in dispersed systems, cyclodextrin can enhance drug solubility, drug stability and drug loading. Interestingly, cyclodextrins themselves can also be employed to form or stabilise dispersed systems (material or emulsifying agent). For example, the interactions between cyclodextrins with components of the vegetable oils (more especially with triglycerides) allow to stabilise simple or multiple emulsions but also to form particles called "beads". Very rich in oil, this novel lipid carrier presents an important potential for the encapsulation of highly lipophilic compounds and their delivery by topical and oral routes. These two applications are more particularly developed in the present paper. PMID:19900602

  19. Synthesis of amorphous calcium phosphate using various types of cyclodextrins

    SciTech Connect

    Li Yanbao; Wiliana, Tjandra; Tam, Kam C. . E-mail: mkctam@ntu.edu.sg

    2007-05-03

    Amorphous calcium phosphate (ACP) was synthesised in aqueous solution at room temperature using cyclodextrins. Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX) and thermal analysis (DTA/TGA) were performed on the calcium phosphate precipitates obtained from solutions. We observed that only {beta}-CD could stabilise the amorphous phase in the mother solution because of the lower solubility of {beta}-CD in water and the ACP remained stable in aqueous solution for more than 24 h at room temperature. The ACP particle has an initial particle size of less than 40 nm, Ca/P molar ratio of 1.67 and {beta}-CD absorbed on its surface. The mechanism for the stabilisation of ACP is proposed.

  20. Cyclodextrin-Templated Porphyrin Nanorings**

    PubMed Central

    Liu, Pengpeng; Neuhaus, Patrik; Kondratuk, Dmitry V; Balaban, T Silviu; Anderson, Harry L

    2014-01-01

    α- and β-Cyclodextrins have been used as scaffolds for the synthesis of six- and seven-legged templates by functionalizing every primary CH2OH with a 4-pyridyl moiety. Although these templates are flexible, they are very effective for directing the synthesis of macrocyclic porphyrin oligomers consisting of six or seven porphyrin units. The transfer of chirality from the cyclodextrin templates to their nanoring hosts is evident from NMR and circular dichroism spectroscopy. Surprisingly, the mean effective molarity for binding the flexible α-cyclodextrin-based template within the six-porphyrin nanoring (74 m) is almost as high as for the previously studied rigid hexadentate template (180 m). The discovery that flexible templates are effective in this system, and the availability of a template with a prime number of binding sites, open up many possibilities for the template-directed synthesis of larger macrocycles. PMID:24916813

  1. Cyclodextrin-templated porphyrin nanorings.

    PubMed

    Liu, Pengpeng; Neuhaus, Patrik; Kondratuk, Dmitry V; Balaban, T Silviu; Anderson, Harry L

    2014-07-21

    α- and β-cyclodextrins have been used as scaffolds for the synthesis of six- and seven-legged templates by functionalizing every primary CH2OH with a 4-pyridyl moiety. Although these templates are flexible, they are very effective for directing the synthesis of macrocyclic porphyrin oligomers consisting of six or seven porphyrin units. The transfer of chirality from the cyclodextrin templates to their nanoring hosts is evident from NMR and circular dichroism spectroscopy. Surprisingly, the mean effective molarity for binding the flexible α-cyclodextrin-based template within the six-porphyrin nanoring (74 M) is almost as high as for the previously studied rigid hexadentate template (180 M). The discovery that flexible templates are effective in this system, and the availability of a template with a prime number of binding sites, open up many possibilities for the template-directed synthesis of larger macrocycles. PMID:24916813

  2. Thermal and pH stability of "beta-benzyme".

    PubMed Central

    D'Souza, V T; Lu, X L; Ginger, R D; Bender, M L

    1987-01-01

    The thermal and pH stability of "beta-benzyme", an artificial chymotrypsin based on beta-cyclodextrin, has been studied and compared with the stability of real chymotrypsin. Artificial chymotrypsin is vastly superior to real chymotrypsin with regard to both temperature and pH stability. The reasons for this increased stability are discussed. PMID:3468505

  3. Cyclodextrin assisted nanophase determination of alkaloid salts.

    PubMed

    Csernák, Orsolya; Buvári-Barcza, Agnes; Barcza, Lajos

    2006-04-15

    The poor water solubility of the free base and the high dissociation constant (K(a)) hinder mainly the assay of alkaloid salts. We have elaborated an environment friendly method that can be carried out in aqueous media. The stability difference of the cyclodextrin (CD) complexes of free and protonated bases were used for this purpose. The base is included into the hydrophobic cavity of the CD (which serves as an apolar solvent phase on molecular level) and its solubility in water is increased. Since the base forms more stable inclusion complex than its protonated species, the pK(a) is decreased and the potentiometric titration is promoted by this way, too. Six different hydrohalide alkaloid salts have been investigated and the most appropriate CDs were chosen (depending on the size of the molecules and/or substituents). The results of the assays agree well with those obtained by the direct nonaqueous titrations. The stability constants of the inclusion complexes have been also computed. PMID:18970584

  4. β-cyclodextrin assistant flavonoid glycosides enzymatic hydrolysis

    PubMed Central

    Jin, Xin; Zhang, Zhen-hai; Sun, E.; Jia, Xiao-Bin

    2013-01-01

    Background: The content of icaritin and genistein in herba is very low, preparation with relatively large quantities is an important issue for extensive pharmacological studies. Objective: This study focuses on preparing and enzymic hydrolysis of flavonoid glycosides /β-cyclodextrin inclusion complex to increase the hydrolysis rate. Materials and Methods: The physical property of newly prepared inclusion complex was tested by differential scanning calorimetry (DSC). The conditions of enzymatic hydrolysis were optimized for the bioconversion of flavonoid glycosides /β-cyclodextrin inclusion complex by mono-factor experimental design. The experiments are using the icariin and genistein as the model drugs. Results: The solubility of icariin and genistein were increased almost 17 times from 29.2 μg/ml to 513.5 μg/ml at 60°C and 28 times from 7.78 μg/ml to 221.46 μg/ml at 50°C, respectively, demonstrating that the inclusion complex could significantly increase the solubility of flavonoid glycosides. Under the optimal conditions, the reaction time of icariin and genistin decreased by 68% and 145%, when compared with that without β-CD inclusion. By using this enzymatic condition, 473 mg icaritin (with the purity of 99.34%) and 567 mg genistein(with the purity of 99.46%), which was finally determined by melt point, ESI-MS, UV, IR, 1H NMR and 13C NMR, was obtained eventually by transforming the inclusion complex(contains 1.0 g substrates). Conclusion: This study can clearly indicate a new attempt to improve the speed of enzyme-hydrolysis of poorly water-soluble flavonoid glycosides and find a more superior condition which is used to prepare icaritin and genistein. PMID:24143039

  5. The Inclusive Classroom: How Inclusive Is Inclusion?

    ERIC Educational Resources Information Center

    Reid, Claudette M.

    2010-01-01

    This paper presents the position that inclusion is limited; inclusion does not go far enough. The inclusive classroom has been assessed to be of benefit both to the teacher and student. There are, however, limits set on inclusion. In most classrooms only children with learning disability are included omitting those with severe disabilities,…

  6. Complexation of the sunscreen agent, 4-methylbenzylidene camphor with cyclodextrins: effect on photostability and human stratum corneum penetration.

    PubMed

    Scalia, Santo; Tursilli, Rosanna; Iannuccelli, Valentina

    2007-05-01

    The interaction between the sunscreen agent, 4-methylbenzylidene camphor (4-MBC) and hydrophilic alpha-, beta- and gamma-cyclodextrin derivatives was investigated in water by phase-solubility analysis. Among the studied cyclodextrins, random methyl-beta-cyclodextrin (RM-beta-CD) had the greatest solubilizing activity. The complexation of the sunscreen agent with RM-beta-CD was confirmed by nuclear magnetic resonance spectroscopy and powder X-ray diffractometry. The light-induced decomposition of 4-MBC in emulsion vehicles was markedly decreased by complexation with RM-beta-CD (the extent of degradation, determined by HPLC, was 7.1% for the complex compared to 21.1% for free 4-MBC). The influence of RM-beta-CD on the human skin penetration of the sunscreen was investigated in vivo using the tape stripping method, a useful procedure for selectively removing the outermost cutaneous layers. Considerable quantities (21.2-25.1% of the applied dose) of 4-MBC permeated in the stratum corneum. However, no significant differences in the amounts of UV filter in the 10 first strips of the horny layer were observed between the formulations containing 4-MBC free or complexed with RM-beta-CD. Therefore, RM-beta-CD complexation did not alter the retention of 4-MBC in the superficial layers of the stratum corneum, where its action is more desirable. PMID:17291707

  7. Removal of volatile organic compounds using amphiphilic cyclodextrin-coated polypropylene.

    PubMed

    Lumholdt, Ludmilla; Fourmentin, Sophie; Nielsen, Thorbjørn T; Larsen, Kim L

    2014-01-01

    Polypropylene nonwovens were functionalised using a self-assembled, amphiphilic cyclodextrin coating and the potential for water purification by removal of pollutants was studied. As benzene is one of the problematic compounds in the Water Framework Directive, six volatile organic compounds (benzene and five benzene-based substances) were chosen as model compounds. The compounds were tested as a mixture in order to provide a more realistic situation since the wastewater will be a complex mixture containing multiple pollutants. The volatile organic compounds are known to form stable inclusion complexes with cyclodextrins. Six different amphiphilic cyclodextrin derivatives were synthesised in order to elucidate whether or not the uptake abilities of the coating depend on the structure of the derivative. Headspace gas chromatography was used for quantification of the uptake exploiting the volatile nature of benzene and its derivatives. The capacity was shown to increase beyond the expected stoichiometries of guest-host complexes with ratios of up to 16:1. PMID:25550739

  8. Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations.

    PubMed

    Raffaini, Giuseppina; Mazzaglia, Antonino; Ganazzoli, Fabio

    2015-01-01

    Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a "bottom up" approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties. PMID:26734094

  9. Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

    PubMed Central

    Mazzaglia, Antonino; Ganazzoli, Fabio

    2015-01-01

    Summary Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties. PMID:26734094

  10. Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray.

    PubMed

    Loftsson, T; Gudmundsdóttir, H; Sigurjónsdóttir, J F; Sigurdsson, H H; Sigfússon, S D; Másson, M; Stefánsson, E

    2001-01-01

    The cyclodextrin solubilization of three benzodiazepines, i.e. alprazolam, midazolam and triazolam, was investigated. The cyclodextrin solubilization was enhanced through ring-opening of the benzodiazepine rings and ionization of the ring-open forms. Additional enhancement was obtained through interaction of a water-soluble polymer with the cyclodextrin complexes. The ring-opening was pH-dependent and completely reversible, the ring-open forms dominating at low pH but the ring-closed forms at physiologic pH. The ring-closed forms were rapidly regenerated upon elevation of pH. In freshly collected human serum in vitro at 37 degrees C, the half-life for the first-order rate constant for the ring-closing reaction was estimated to be less than 2 min for both alprazolam and midazolam. Midazolam (17 mg/ml) was solubilized in aqueous pH 4.3 nasal formulation containing 14% (w/v) sulfobutylether beta-cyclodextrin, 0.1% (w/v) hydroxypropyl methylcellulose, preservatives and buffer salts. Six healthy volunteers received 0.06 mg/kg midazolam intranasally and 2 mg intravenously, and blood samples were collected up to 360 min after the administration. Midazolam was absorbed rapidly reaching maximum serum concentrations of 54.3+/-5.0 ng/ml at 15+/-2 min. The elimination half-life of midazolam was 2.2+/-0.3 h and the absolute availability was 73+/-7%. All mean values+/-SEM. PMID:11165818

  11. Characterization of pioglitazone cyclodextrin complexes: Molecular modeling to in vivo evaluation

    PubMed Central

    Bramhane, Dinesh M.; Kulkarni, Preethi A.; Martis, Elvis A. F.; Pissurlenkar, Raghuvir R. S.; Coutinho, Evans C.; Nagarsenker, Mangal S.

    2016-01-01

    Aims: The objective of present study was to study the influence of different β-cyclodextrin derivatives and different methods of complexation on aqueous solubility and consequent translation in in vivo performance of Pioglitazone (PE). Material and Methods: Three cyclodextrins: β-cyclodextrin (BCD), hydroxypropyl-β-cyclodextrin (HPBCD) and Sulfobutylether-7-β-cyclodextrin (SBEBCD) were employed in preparation of 1:1 Pioglitazone complexes by three methods viz. co-grinding, kneading and co-evaporation. Complexation was confirmed by phase solubility, proton NMR, Fourier Transform Infrared spectroscopy, Differential Scanning Calorimetry (DSC) and X-Ray diffraction (XRD). Mode of complexation was investigated by molecular dynamic studies. Pharmacodynamic study of blood glucose lowering activity of PE complexes was performed in Alloxan induced diabetic rat model. Results: Aqueous solubility of PE was significantly improved in presence of cyclodextrin. Apparent solubility constants were observed to be 254.33 M–1 for BCD-PE, 737.48 M–1 for HPBCD-PE and 5959.06 M–1 for SBEBCD-PE. The in silico predictions of mode of inclusion were in close agreement with the experimental proton NMR observation. DSC and XRD demonstrated complete amorphization of crystalline PE upon inclusion. All complexes exhibited >95% dissolution within 10 min compared to drug powder that showed <40% at the same time. Marked lowering of blood glucose was recorded for all complexes. Conclusion: Complexation of PE with different BCD significantly influenced its aqueous solubility, improved in vitro dissolution and consequently translated into enhanced pharmacodynamic activity in rats PMID:27134470

  12. Selective isolation of gold facilitated by second-sphere coordination with α-cyclodextrin

    PubMed Central

    Liu, Zhichang; Frasconi, Marco; Lei, Juying; Brown, Zachary J.; Zhu, Zhixue; Cao, Dennis; Iehl, Julien; Liu, Guoliang; Fahrenbach, Albert C.; Botros, Youssry Y.; Farha, Omar K.; Hupp, Joseph T.; Mirkin, Chad A.; Fraser Stoddart, J.

    2013-01-01

    Gold recovery using environmentally benign chemistry is imperative from an environmental perspective. Here we report the spontaneous assembly of a one-dimensional supramolecular complex with an extended {[K(OH2)6][AuBr4](α-cyclodextrin)2}n chain superstructure formed during the rapid co-precipitation of α-cyclodextrin and KAuBr4 in water. This phase change is selective for this gold salt, even in the presence of other square-planar palladium and platinum complexes. From single-crystal X-ray analyses of six inclusion complexes between α-, β- and γ-cyclodextrins with KAuBr4 and KAuCl4, we hypothesize that a perfect match in molecular recognition between α-cyclodextrin and [AuBr4]− leads to a near-axial orientation of the ion with respect to the α-cyclodextrin channel, which facilitates a highly specific second-sphere coordination involving [AuBr4]− and [K(OH2)6]+ and drives the co-precipitation of the 1:2 adduct. This discovery heralds a green host–guest procedure for gold recovery from gold-bearing raw materials making use of α-cyclodextrin—an inexpensive and environmentally benign carbohydrate. PMID:23673640

  13. Modulating Pluronics micellar rupture with cyclodextrins and drugs: effect of pH and temperature

    NASA Astrophysics Data System (ADS)

    Valero, M.; Dreiss, C. A.

    2014-11-01

    Micelles of the triblock copolymer Pluronic F127 can encapsulate drugs with various chemical structures and their architecture has been studied by small-angle neutron scattering (SANS). Interaction with a derivative of β-cyclodextrin, namely, heptakis(2,6-di-O- methyl)-β-cyclodextrin (DIMEB), induces a complete break-up of the micelles, providing a mechanism for drug release. In the presence of drugs partitioned within the micelles, competitive interactions between polymer, drug and cyclodextrin lead to a modulation of the micellar rupture, depending on the nature of the drug and the exact composition of the ternary system. These interactions can be further adjusted by temperature and pH. While the most widely accepted mechanism for the interaction between Pluronics and cyclodextrins is through polypseudorotaxane (PR) formation, involving the threading of β-CD on the polymer backbone, time-resolved SANS experiments show that de-micellisation takes place in less than 100 ms, thus unambiguously ruling out an inclusion complex between the cyclodextrin and the polymer chains.

  14. Thermodynamic origin of selective binding of β-cyclodextrin derivatives with chiral chromophoric substituents toward steroids.

    PubMed

    Chen, Yong; Li, Fang; Liu, Bo-Wen; Jiang, Bang-Ping; Zhang, Heng-Yi; Wang, Li-Hua; Liu, Yu

    2010-12-16

    Two β-cyclodextrin derivatives with chiral chromophoric substituents, that is, L- (1) and D-tyrosine-modified β-cyclodextrin (2), were synthesized and fully characterized. Their inclusion modes, binding abilities, and molecular selectivities with four steroid guests, that is, cholic acid sodium salt (CA), deoxycholic acid sodium salt (DCA), glycochoic acid sodium salt (GCA), and taurocholic acid sodium salt (TCA), were investigated by the circular dichroism, 2D NMR, and isothermal titration microcalorimetry (ITC). The results obtained from the circular dichroism and 2D NMR showed that two hosts adopted the different binding geometry, and these differences subsequently resulted in the significant differences of molecular binding abilities and selectivities. As compared with native β-cyclodextrin and tryptophan-modified β-cyclodextrin, host 2 showed the enhanced binding abilities for CA and DCA but the decreased binding abilities for GCA and TCA; however, host 1 showed the decreased binding abilities for all four bile salts. The best guest selectivity and the best host selectivity were K(S)(2-DCA)/K(S)(2-TCA) = 12.6 and K(S)(2-CA)/K(S)(1-CA) = 10, respectively, both exhibiting great enhancement as compared with the corresponding values of the previously reported L- and D-tryptophan-modified β-cyclodextrins. Thermodynamically, it was the favorable enthalpic gain that led to the high guest selectivity and host selectivity. PMID:20695496

  15. Influence of β-cyclodextrin on the Properties of Norfloxacin Form A.

    PubMed

    Chierentin, Lucas; Garnero, Claudia; Chattah, Ana Karina; Delvadia, Poonam; Karnes, Thomas; Longhi, Marcela Raquel; Salgado, Hérida Regina Nunes

    2015-06-01

    Cyclodextrins are able to form host-guest complexes with hydrophobic molecules to result in the formation of inclusion complexes. The complex formation between norfloxacin form A and β-cyclodextrin was studied by exploring its structure affinity relationship in an aqueous solution and in the solid state. Kneading, freeze-drying, and physical mixture methods were employed to prepare solid complexes of norfloxacin and β-cyclodextrin. The solubility of norfloxacin significantly increased upon complexation with β-cyclodextrin as demonstrated by a solubility isotherm of the AL type along with the results of an intrinsic dissolution study. The complexes were also characterized in the solid stated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffractometry, scanning electron microscopy (SEM), and solid-state nuclear magnetic resonance (ssNMR) spectrometry. The thermal analysis showed that the thermal stability of the drug is enhanced in the presence of β-cyclodextrin. Finally, the microbiological studies showed that the complexes have better potency when compared with pure drug. PMID:25511811

  16. Physical Characterisation as an Insight into a Gene Delivery System Containing Cyclodextrins with Pluronic®-F127 and Folic acid as Non-Viral Vectors.

    PubMed

    Eng, Matthew; Elkordy, Amal A; McCarron, Paul A; Elkordy, Eman A; Faheem, Ahmed

    2014-01-01

    Gene delivery into cells offers opportunities to treat various human genetic diseases. Effective gene delivery is dependent on its stability and ability to transfect across cells. DNA is susceptible to enzymatic degradation and its negatively charge are barriers towards successful transfection. DNA has to be protected from degradation and neutralised. Non-viral vectors are preferred carrier systems, therefore, the use of cyclodextrins with Pluronic(®)-F127 and folic acid at different concentrations to stabilise the formulation was investigated. Formulations were characterised in fresh and freeze dried forms. DNA stability in formulations was tested by determining the stability of DNA against enzymatic degradation. Degree of DNA inclusion into cyclodextrins was investigated using fluorescence spectroscopy. Thermal behaviour was studied using Differential Scanning Calorimetry (DSC). Incorporation of Pluronic(®)-F127 produced most stable formulations regarding enzymatic degradation. These formulations show high percentage inclusion. Shift of peaks in FTIR data, appearance of uniform particulate as detected by SEM and changing in the denaturation temperature as demonstrated by DSC data for Pluronic(®)-F127 containing formulations confirm clear interaction between Pluronic(®)-F127 and cyclodextrin/ DNA complex. It was noted that γ-cyclodextrin provide better protection and inclusion compared to β-cyclodextrin. Pluronic(®)-F127 with cyclodextrins is a promising combination to improve stability. PMID:25158973

  17. Dissolution enhancement of cefdinir with hydroxypropyl-β-cyclodextrin.

    PubMed

    Guo, Bohong; Zhong, Shufen; Li, Niying; Li, Xiaofang; Yi, Jun; Jin, Miaozhen

    2013-11-01

    The solid state properties and dissolution behavior of binary systems of cefdinir (CEF) with hydroxypropyl-β-cyclodextrin (HP-β-CD) were investigated. CEF-HP-β-CD interaction in the solution state was studied by phase-solubility analysis and demonstrates the ability of HP-β-CD to complex with CEF giving A(L) type profile with 65.28 ± 1.3 M⁻¹ stability constant. The freeze drying technique was adopted to prepare binary systems of CEF with HP-β-CD in 1:1 molar ratio. The solid inclusion was characterized by fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRD), and scanning electron microscopy (SEM). Aqueous solubility of CEF-HP-β-CD inclusion complex was 2.36-fold of pure CEF. The dissolution profiles of inclusion complexes were determined and compared with those of CEF alone and their physical mixtures. The dissolution rate of inclusion complex was superior than the CEF alone. These approaches indicated that CEF was able to form an inclusion complex with HP-β-CD, and the inclusion compounds exhibited different spectroscopic features and properties. PMID:24087855

  18. Photophysical studies of six amphiphilic 2:1 cyclodextrin:[60]fullerene derivatives

    NASA Astrophysics Data System (ADS)

    Quaranta, Annamaria; Zhang, Yongmin; Filippone, Salvatore; Yang, Juan; Sinaÿ, Pierre; Rassat, André; Edge, Ruth; Navaratnam, Suppiah; McGarvey, David J.; Land, Edward J.; Brettreich, Michael; Hirsch, Andreas; Bensasson, René V.

    2006-06-01

    In search of a simple internal complexation of C 60 in cyclodextrins, six 2:1 cyclodextrin:[60]fullerene conjugates involving different types of linkers have been synthesised. Using spectrophotometry, laser flash photolysis and pulse radiolysis, we have investigated spectroscopic and photophysical properties of these 2:1 cyclodextrin [60]fullerene monoadduct conjugates ( CDF), including ground and triplet state absorption spectra, triplet molar absorption coefficients ( ɛT), quantum yields of triplet ( ΦT) and singlet oxygen formation ( ΦΔ) in water and toluene, in order to probe the possibility of 2:1 inclusion complexes of C 60 between two cyclodextrins. In water, the CDF spectroscopic and photophysical properties indicate hydrophobically driven self-assemblies of the amphiphilic conjugates into spherical micelles with no evidence for the presence of a 2:1 inclusion complex, while in toluene they show no sign of aggregation. It is observed that formation of aggregates in water does not prevent scavenging of HO rad radical by the C 60 moiety of the CD-C 60 conjugates.

  19. Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin.

    PubMed

    Liu, Meina; Cao, Wen; Sun, Yinghua; He, Zhonggui

    2014-12-30

    The therapeutic efficacy of repaglinide (RPG) is limited by the low and variable oral bioavailability owing to its limited aqueous solubility. In our present study, the development and evaluation of inclusion complex applying hydroxypropyl-β-cyclodextrin (HP-β-CD) for the improvement of oral bioavailability of repaglinide was investigated systematically. The inclusion complex of repaglinide was prepared by lyophilization technique using drug: hydroxypropyl-β-cyclodextrin (1:15 mole). The prepared complexation was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), NMR spectroscopy and evaluated by dissolution studies. The (1)H NMR was used in the structure study of repaglinide-HP-β-CD (RPG-HP-β-CD) inclusion complex. The analysis proved the higher probability of the repaglinide A-ring into the narrow rim of the β-cyclodextrin molecule. All the characterization information confirmed the formation of RPG-HP-β-CD inclusion complex. The in vivo pharmacokinetics of RPG-HP-β-CD and their physical mixture were performed in beagle dogs. For the first time, a simple, rapid, and sensitive LC-MS/MS method for determination of RPG in beagle dog plasma was developed. The Cmax and AUC0-t of RPG-HP-β-CD were 2.5 and 2 times higher than that of the physical mixture. These results suggested that the interaction of repaglinide with HP-β-CD could notably improve the dissolution rate and bioavailability of repaglinide comparing with its physical mixture. PMID:25455768

  20. Green extraction of polyphenols from whole pomegranate fruit using cyclodextrins.

    PubMed

    Diamanti, Amalia C; Igoumenidis, Panagiotis E; Mourtzinos, Ioannis; Yannakopoulou, Konstantina; Karathanos, Vaios T

    2017-01-01

    Pomegranate is a source of bioactive phytochemicals. The objective of this study was the derivation of a sustainable method to exploit the whole fruit, both edible and non-edible parts, as a source of polyphenols. Pomegranate peel contains a 10-fold higher phenolic content than the pulp. The fruit was freeze-dried and the resulting dry matter was extracted with solid-liquid percolation equipment using non-toxic and eco-friendly extraction solvents: either deionized water or aqueous solutions of cyclodextrins. Cyclodextrins (CDs) are known molecular encapsulators and our results prove enhancement of the extraction of pomegranate polyphenols by 20%. In order to examine the formation of inclusion complexes between CD's and polyphenols of the extract, polyphenols were isolated using solid-phase extraction. NMR studies with the purified extracts and the individual CDs confirmed inclusion complex formation in water. Pomegranate liquid extracts may be used as raw materials for several end-users in the food, cosmetic and pharmaceutical industries. PMID:27507448

  1. Supramolecular cyclodextrin-based drug nanocarriers.

    PubMed

    Simões, Susana M N; Rey-Rico, Ana; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2015-04-14

    Supramolecular systems formed by the binding of several cyclodextrins (CDs) to polymers or lipids, either via non-covalent or covalent links, open a wide range of possibilities for the delivery of active substances. CDs can perform as multifunctionalizable cores to which very diverse (macro)molecules and drugs can be conjugated. Grafting with amphiphilic molecules can lead to nanoassemblies exhibiting a variety of architectures. CDs can also polymerize with other CDs or can be used to functionalize preexisting polymers to form polymers/networks with enhanced capability to form inclusion complexes. Alternatively, CDs can be exploited as transient cross-linkers to form poly(pseudo)rotaxane-based networks or zipper-like assemblies. Combination of mutifunctionality and complexation ability of CDs has been shown to be useful to develop depot-like formulations and colloidal nanocarriers with improved performances regarding easiness of administration, protection of the encapsulated substances, control of the delivery rate, and cell interactions. The aim of this review is to provide an overall view of the diversity of designs of CD-based supramolecular nanosystems with a special focus on the advances materialized in the last five years, including clinical trials. PMID:25679097

  2. Preparation and characterization of starch/cyclodextrin bioadhesive microspheres as platform for nasal administration of Gabexate Mesylate (Foy) in allergic rhinitis treatment.

    PubMed

    Fundueanu, Gheorghe; Constantin, Marieta; Dalpiaz, Alessandro; Bortolotti, Fabrizio; Cortesi, Rita; Ascenzi, Paolo; Menegatti, Enea

    2004-01-01

    Bioadhesive and biodegradable microspheres were obtained by chemical cross-linking with epichlorohydrin of an alkaline solution of a mixture of starch and alpha-, beta-, or gamma-cyclodextrin (CyD). Microspheres were characterized by scanning electron microscopy, swelling degree, and water retention. The percentage of the effective CyD in microspheres was estimated by measuring the amount of iodine and typical organic compounds (TOCs) retained in the hydrophobic cavity of CyD. Gabexate Mesylate (trade name Foy); GM), an antiallergic drug, was included in microspheres by soaking in an aqueous solution containing the drug, followed by solvent evaporation or lyophilization. UV, IR, and DSC data indicated that despite the fact that GM is a hydrophilic drug, its hydrophobic moiety close to the benzene ring is able to penetrate the CyD cavity and to form stable inclusion complexes. Values of the association equilibrium constant for GM binding to CyD, obtained by UV differential spectroscopy, indicated that the affinity of the drug for alpha- and gamma-CyD is higher than that for beta-CyD. In vitro, GM was gradually released during 1h. Even if the release rate of the drug is relatively fast, the microspheres might actually provide the best platform since the material adheres to the nasal mucosa which was proved by adhesion tests. The GM integrity was checked by comparing its anti-trypsin activity before and after release. PMID:14580919

  3. Molecular Processing of Polymers with Cyclodextrins

    NASA Astrophysics Data System (ADS)

    Tonelli, Alan E.

    We summarize our recent studies employing the cyclic starch derivatives called cyclodextrins (CDs) to both nanostructure and functionalize polymers. Two important structural characteristics of CDs are taken advantage of to achieve these goals. First the ability of CDs to form noncovalent inclusion complexes (ICs) with a variety of guest molecules, including many polymers, by threading and inclusion into their relatively hydrophobic interior cavities, which are roughly cylindrical with diameters of ˜ 0.5 - 1.0 nm. α-, β-, and γ-CD contain six, seven, and eight α-1,4-linked glucose units, respectively. Warm water washing of polymer-CD-ICs containing polymer guests insoluble in water or treatment with amylase enzymes serves to remove the host CDs and results in the coalescence of the guest polymers into solid samples. When guest polymers are coalesced from the CD-ICs by removing their host CDs, they are observed to solidify with structures, morphologies, and even conformations that are distinct from bulk samples made from their solutions and melts. Molecularly mixed, intimate blends of two or more polymers that are normally immiscible can be obtained from their common CD-ICs, and the phase segregation of incompatible blocks can be controlled (suppressed or increased) in CD-IC coalesced block copolymers. In addition, additives may be more effectively delivered to polymers in the form of their crystalline CD-ICs or soluble CD-rotaxanes. Secondly, the many hydroxyl groups attached to the exterior rims of CDs, in addition to conferring water solubility, provide an opportunity to covalently bond them to polymers either during their syntheses or via postpolymerization reactions. Polymers containing CDs in their backbones or attached to their side chains are observed to more readily accept and retain additives, such as dyes and fragrances. Processing with CDs can serve to both nanostructure and functionalize polymers, leading to greater understanding of their behaviors

  4. Complexation of Statins with β-Cyclodextrin in Solutions of Small Molecular Additives and Macromolecular Colloids

    NASA Astrophysics Data System (ADS)

    Süle, András; Csempesz, Ferenc

    The solubility of lovastatin and simvastatin (inevitable drugs in the management of cardiovascular diseases) was studied by phase-solubility measurements in multicomponent colloidal and non-colloidal media. Complexation in aqueous solutions of the highly lipophilic statins with β-cyclodextrin (β-CD) in the absence and the presence of dissolved polyvinyl pyrrolidone, its monomeric compound, tartaric acid and urea, respectively, were investigated. For the characterization of the CD-statin inclusion complexes, stability constants for the associates have been calculated.

  5. Intermolecular interactions in rifabutin-2-hydroxypropyl-β-cyclodextrin-water solutions, according to solubility data

    NASA Astrophysics Data System (ADS)

    Anshakova, A. V.; Vinogradov, E. V.; Sedush, N. G.; Kurtikyan, T. S.; Zhokhov, S. S.; Polshakov, V. I.; Ermolenko, Yu. V.; Konyukhov, V. Yu.; Maksimenko, O. O.; Gelperin, S. E.

    2016-05-01

    The formulations of rifabutin (RB) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), obtained using different preparation techniques, are studied by means of differential scanning calorimetry and molecular spectroscopy (FTIR, NMR, Raman scattering, and photon correlation light scattering). It is established that molecules of RB do not form inclusion complexes with the molecules of HP-β-CD, and an increase in the solubility of RB determined earlier is caused by the formation of weak intermolecular associates.

  6. Chiral separation of deprenyl-N-oxide isomers by capillary electrophoresis using various cyclodextrin derivatives.

    PubMed

    Tábi, Tamás; Halász, Attila Sándor; Pálfi, Melinda; Magyar, Kálmán; Szöko, Eva

    2004-01-01

    Chiral separation of deprenyl-N-oxide isomers is presented using capillary electrophoresis in the presence of various cyclodextrin (CD) derivatives. This recently identified metabolite of R-(-)-deprenyl may possess desirable pharmacological activities. The effect of the cavity size and the substituents of the CD are examined on the enantiomer resolution of the compound having an asymmetric center on a heteroatom. The importance of hydrophilic or hydrogen bonding interaction, as well as the position of the interacting groups is demonstrated. Outstanding selectivity and resolution values are achieved using the chargeable carboxymethyl-beta-CD. 2-Hydroxypropyl-beta-CD is also suitable for the enantiomer separation of the analyte. Native beta-CD and carboxyethyl-beta-CD provide only poor enantioselectivity, whereas heptakis-(2,6-di-O-methyl)-beta-CD is capable of separating only the diastereomers. No chiral resolution can be observed in the presence of gamma-CD. PMID:14965411

  7. Synthesis of cationic single-isomer cyclodextrins for the chiral separation of amino acids and anionic pharmaceuticals.

    PubMed

    Tang, Weihua; Ng, Siu-Choon

    2007-01-01

    We describe a protocol for the synthesis of mono-6(A)-(1-butyl-3-imidazolium)-6(A)-deoxy-beta-cyclodextrin chloride (BIMCD), a cationic, water-soluble cyclodextrin used in the chiral separation of amino acids and anionic pharmaceuticals by capillary electrophoresis. Starting from commercially available chemicals, BIMCD is synthesized in five steps. The first step involves a nucleophilic substitution between p-toluenesulfonyl chloride and imidazole to afford 1-(p-toluenesulfonyl)imidazole (A). In the second step, a nucleophilic substitution between beta-cyclodextrin and A affords mono-6(A)-(p-toluenesulfonyl)-6(A)-deoxy-beta-cyclodextrin (B). In the third step, a nucleophilic substitution between 1-bromobutane and imidazole affords 1-butylimidazole (C). In the fourth step, a nucleophilic addition between A and C affords BIMCD tosylate. In the final step, anion exchange using an ion-exchange resin yields BIMCD as a highly water-soluble solid. Each step takes up to 2 d, including the time required for product purification. The overall protocol requires approximately 6 d. PMID:18079719

  8. Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin

    PubMed Central

    Sangpheak, Waratchada; Kicuntod, Jintawee; Schuster, Roswitha; Rungrotmongkol, Thanyada; Wolschann, Peter; Kungwan, Nawee; Viernstein, Helmut

    2015-01-01

    Summary The aim of this work is to improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with β-cyclodextrin (β-CD) and its methylated derivatives (2,6-di-O-methyl-β-cyclodextrin, DM-β-CD and randomly methylated-β-CD, RAMEB). The free energies of inclusion complexes between hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest–host interaction when hesperetin binds with CDs. The phase solubility diagram showed the formation of a soluble complex of AL type, with higher increase in solubility and stability when hesperetin and naringenin were complexed with RAMEB. Solid complexes were prepared by freeze-drying, and the data from differential scanning calorimetry (DSC) confirmed the formation of inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs. PMID:26877798

  9. Inclusion of cut and as-grown single-walled carbon nanotubes in the helical superstructure of schizophyllan and curdlan (beta-1,3-glucans).

    PubMed

    Numata, Munenori; Asai, Masayoshi; Kaneko, Kenji; Bae, Ah-Hyun; Hasegawa, Teruaki; Sakurai, Kazuo; Shinkai, Seiji

    2005-04-27

    We have found that single-chain schizophyllan and curdlan (s-SPG and s-curdlan, respectively) can dissolve as-grown and cut single-walled carbon nanotubes (ag-SWNTs and c-SWNTs, respectively) in aqueous solution. The vis-NIR spectra of the composites suggest that c-SWNTs are dissolved as a bundle, whereas ag-SWNTs exist as one or only a few pieces in the tubular hollow constructed by the helical structure inherent to these beta-1,3-glucans. EDX and CLSM measurements and TEM observation established that the distribution map of these polysaccharides overlaps well with the image of SWNTs, indicating that these two components form a composite. Very interestingly, when c-SWNTs were dissolved with the aid of s-SPG or s-curdlan in water, a clear periodical structure with inclined stripes, as detected by AFM, appeared on the fibrous composite surface. Because this periodical structure has never been recognized for the composites with other water-soluble polymers, one can regard that s-SPG or s-curdlan wraps c-SWNTs constructing a helically twined structure. High-resolution TEM observation of an ag-SWNTs/s-SPG composite gave a clearer image in that two s-SPG chains twine one ag-SWNT and the helical motif is right-handed. When this sample was subjected to the AFM measurement, the composite showed the 2-3 nm height. This height implies that one piece of ag-SWNT is included in the s-SPGs helical structure. As a summary, it has been established that beta-1,3-glucans such as s-SPG and s-curdlan not only dissolve SWNTs but also create a novel superstructure on the surface. PMID:15839686

  10. Thiolated Cyclodextrin: Development of a Mucoadhesive Vaginal Delivery System for Acyclovir.

    PubMed

    Ijaz, Muhammad; Griessinger, Julia Anita; Mahmood, Arshad; Laffleur, Flavia; Bernkop-Schnürch, Andreas

    2016-05-01

    The objective of this study was the development of a mucoadhesive vaginal delivery system for acyclovir (Acv). Sodium-per-iodate (NaIO4) was used to introduce aldehyde substructures into beta-cyclodextrin (β-CD) by oxidative cleavage of vicinal diol bonds. Cysteamine was covalently attached to β-CD-CHO via reductive amination. Ellman's reagent was utilized for quantification of free thiol groups attached and resazurin assay was used for cytotoxicity studies. Mucoadhesive properties were evaluated on porcine vaginal mucosa in comparison to intestinal mucosa. Quantification of thiol groups revealed 851.84 ± 107, 1040.44 ± 132, and 1563.72 ± 171 μmol/g of free thiol groups attached to the β-CD-SH851, β-CD-SH1040, and β-CD-SH1563, respectively. β-CD-SH derivatives at concentrations of 0.5% (m/v) did not show significant reduction of viability of Caco-2 cells within 24 h. Furthermore, water solubility of β-CD-SH1563 was improved 7.6-fold in comparison to unmodified β-CD. β-CD-SH851, β-CD-SH1040, and β-CD-SH1563 showed 5.84-, 15.95-, and 17.14-fold improved mucoadhesive properties on porcine vaginal mucosa and 3-, 12.47-, and 32.13-fold on porcine intestinal mucosa, respectively. Inclusion complex of Acv with β-CD-SH1563 resulted in significantly improved drug dissolution. According to the results, β-CD-SH derivatives might be promising new tools for local vaginal delivery of Acv. PMID:27112405

  11. ESR technique for noninvasive way to quantify cyclodextrins effect on cell membranes

    SciTech Connect

    Grammenos, A.; Mouithys-Mickalad, A.; Guelluy, P.H.; Lismont, M.; Piel, G.; Hoebeke, M.

    2010-07-30

    Research highlights: {yields} ESR: a new tool for cyclodextrins study on living cells. {yields} Cholesterol and phospholipid extraction by Rameb in a dose- and time-dependent way. {yields} Extracted phospholipids and cholesterol form stable aggregates. {yields} ESR spectra show that lipid rafts are damaged by Rameb. {yields} Quantification of the cholesterol extraction on cell membranes in a noninvasive way. -- Abstract: A new way to study the action of cyclodextrin was developed to quantify the damage caused on cell membrane and lipid bilayer. The Electron Spin Resonance (ESR) spectroscopy was used to study the action of Randomly methylated-beta-cyclodextrin (Rameb) on living cells (HCT-116). The relative anisotropy observed in ESR spectrum of nitroxide spin probe (5-DSA and cholestane) is directly related to the rotational mobility of the probe, which can be further correlated with the microviscosity. The use of ESR probes clearly shows a close correlation between cholesterol contained in cells and cellular membrane microviscosity. This study also demonstrates the Rameb ability to extract cholesterol and phospholipids in time- and dose-dependent ways. In addition, ESR spectra enabled to establish that cholesterol is extracted from lipid rafts to form stable aggregates. The present work supports that ESR is an easy, reproducible and noninvasive technique to study the effect of cyclodextrins on cell membranes.

  12. Influence of the preparation method on the physicochemical properties of indomethacin and methyl-β-cyclodextrin complexes.

    PubMed

    Rudrangi, Shashi Ravi Suman; Bhomia, Ruchir; Trivedi, Vivek; Vine, George J; Mitchell, John C; Alexander, Bruce David; Wicks, Stephen Richard

    2015-02-20

    The main objective of this study was to investigate different manufacturing processes claimed to promote inclusion complexation between indomethacin and cyclodextrins in order to enhance the apparent solubility and dissolution properties of indomethacin. Especially, the effectiveness of supercritical carbon dioxide processing for preparing solid drug-cyclodextrin inclusion complexes was investigated and compared to other preparation methods. The complexes were prepared by physical mixing, co-evaporation, freeze drying from aqueous solution, spray drying and supercritical carbon dioxide processing methods. The prepared complexes were then evaluated by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, solubility and dissolution studies. The method of preparation of the inclusion complexes was shown to influence the physicochemical properties of the formed complexes. Indomethacin exists in a highly crystalline solid form. Physical mixing of indomethacin and methyl-β-cyclodextrin appeared not to reduce the degree of crystallinity of the drug. The co-evaporated and freeze dried complexes had a lower degree of crystallinity than the physical mix; however the lowest degree of crystallinity was achieved in complexes prepared by spray drying and supercritical carbon dioxide processing methods. All systems based on methyl-β-cyclodextrin exhibited better dissolution properties than the drug alone. The greatest improvement in drug dissolution properties was obtained from complexes prepared using supercritical carbon dioxide processing, thereafter by spray drying, freeze drying, co-evaporation and finally by physical mixing. Supercritical carbon dioxide processing is well known as an energy efficient alternative to other pharmaceutical processes and may have application for the preparation of solid-state drug-cyclodextrin inclusion complexes. It is an effective and economic method that allows the formation of solid complexes with a

  13. Synergistic effect of cyclodextrins and methyl jasmonate on taxane production in Taxus x media cell cultures.

    PubMed

    Sabater-Jara, Ana-Belén; Onrubia, Miriam; Moyano, Elisabeth; Bonfill, Mercedes; Palazón, Javier; Pedreño, María A; Cusidó, Rosa M

    2014-10-01

    Methyl jasmonate and cyclodextrins are proven effective inducers of secondary metabolism in plant cell cultures. Cyclodextrins, which are cyclic oligosaccharides, can form inclusion complexes with nonhydrophilic secondary products, thus increasing their excretion from the producer cells to the culture medium. In the present work, using a selected Taxus x media cell line cultured in a two-stage system, the relationship between taxane production and the transcript profiles of several genes involved in taxol metabolism was studied to gain more insight into the mechanism by which these two elicitors regulate the biosynthesis and excretion of taxol and related taxanes. Gene expression was not clearly enhanced by the presence of cyclodextrins in the culture medium and variably induced by methyl jasmonate, but when the culture was supplemented with both elicitors, a synergistic effect on transcript accumulation was observed. The BAPT and DBTNBT genes, which encode the last two transferases involved in the taxol pathway, appeared to control limiting biosynthetic steps. In the cell cultures treated with both elicitors, the produced taxanes were found mainly in the culture medium, which limited retroinhibition processes and taxane toxicity for the producer cells. The expression level of a putative ABC gene was found to have increased, suggesting it played a role in the taxane excretion. Taxol biosynthesis was clearly increased by the joint action of methyl jasmonate and cyclodextrins, reaching production levels 55 times higher than in nonelicited cultures. PMID:24909837

  14. Piroxicam-β-Cyclodextrin: A GI Safer Piroxicam

    PubMed Central

    Scarpignato, C

    2013-01-01

    Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro-duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called “inclusion complexes” that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads

  15. Piroxicam-β-cyclodextrin: a GI safer piroxicam.

    PubMed

    Scarpignato, C

    2013-01-01

    Although NSAIDs are very effective drugs, their use is associated with a broad spectrum of adverse reactions in the liver, kidney, cardiovascular (CV) system, skin and gut. Gastrointestinal (GI) side effects are the most common and constitute a wide clinical spectrum ranging from dyspepsia, heartburn and abdominal discomfort to more serious events such as peptic ulcer with life-threatening complications of bleeding and perforation. The appreciation that CV risk is also increased further complicates the choices of physicians prescribing anti-inflammatory therapy. Despite prevention strategies should be implemented in patients at risk, gastroprotection is often underused and adherence to treatment is generally poor. A more appealing approach would be therefore to develop drugs that are devoid of or have reduced GI toxicity. Gastro- duodenal mucosa possesses many defensive mechanisms and NSAIDs have a deleterious effect on most of them. This results in a mucosa less able to cope with even a reduced acid load. NSAIDs cause gastro-duodenal damage, by two main mechanisms: a physiochemical disruption of the gastric mucosal barrier and systemic inhibition of gastric mucosal protection, through inhibition of cyclooxygenase (COX, PG endoperoxide G/H synthase) activity of the GI mucosa. However, against a background of COX inhibition by anti-inflammatory doses of NSAIDs, their physicochemical properties, in particular their acidity, underlie the topical effect leading to short-term damage. It has been shown that esterification of acidic NSAIDs suppresses their gastrotoxicity without adversely affecting anti-inflammatory activity. Another way to develop NSAIDs with better GI tolerability is to complex these molecules with cyclodextrins (CDs), giving rise to so-called "inclusion complexes" that can have physical, chemical and biological properties very different from either those of the drug or the cyclodextrin. Complexation of NSAIDs with β-cyclodextrin potentially leads to a

  16. Divinyl sulfone cross-linked cyclodextrin-based polymeric materials: synthesis and applications as sorbents and encapsulating agents.

    PubMed

    Morales-Sanfrutos, Julia; Lopez-Jaramillo, Francisco Javier; Elremaily, Mahmoud A A; Hernández-Mateo, Fernando; Santoyo-Gonzalez, Francisco

    2015-01-01

    The aim of this study was to evaluate the crosslinking abilities of divinyl sulfone (DVS) for the preparation of novel water-insoluble cyclodextrin-based polymers (CDPs) capable of forming inclusion complexes with different guest molecules. Reaction of DVS with native α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and/or starch generates a variety of homo- and hetero-CDPs with different degrees of crosslinking as a function of the reactants' stoichiometric ratio. The novel materials were characterized by powder X-ray diffraction, electron microscopy and for their sorption of phenol and 4-nitrophenol. They were further evaluated as sorbents with phenolic pollutants (bisphenol A and β-naphthol) and bioactive compounds (the hormone progesterone and curcumin). Data obtained from the inclusion experiments show that the degree of cross-linking has a minor influence on the yield of inclusion complex formation and highlight the important role of the CDs, supporting a sorption process based on the formation of inclusion complexes. In general, the inclusion processes are better described by a Freundlich isotherm although an important number of them can also be fitted to the Langmuir isotherm with R2 ≥ 0.9, suggesting a sorption onto a monolayer of homogeneous sites. PMID:25706758

  17. Inclusion of the Bovine Neutrophil Beta-Defensin 3 with Glycoprotein D of Bovine Herpesvirus 1 in a DNA Vaccine Modulates Immune Responses of Mice and Cattle

    PubMed Central

    Mackenzie-Dyck, Sarah; Kovacs-Nolan, Jennifer; Snider, Marlene; Babiuk, Lorne A.

    2014-01-01

    Bovine herpesvirus 1 (BoHV-1) causes recurrent respiratory and genital infections in cattle and predisposes them to lethal secondary infections. While modified live and killed BoHV-1 vaccines exist, these are not without problems. Development of an effective DNA vaccine for BoHV-1 has the potential to address these issues. As a strategy to enhance DNA vaccine immunity, a plasmid encoding the bovine neutrophil beta-defensin 3 (BNBD3) as a fusion with truncated glycoprotein D (tgD) and a mix of two plasmids encoding BNBD3 and tgD were tested in mice and cattle. In mice, coadministration of BNBD3 on the separate plasmid enhanced the tgD-induced gamma interferon (IFN-γ) response but not the antibody response. BNBD3 fused to tgD did not affect the antibody levels or the number of IFN-γ-secreting cells but increased the induction of tgD-specific cytotoxic T lymphocytes (CTLs). In cattle, the addition of BNBD3 as a fusion construct also modified the immune response. While the IgG and virus-neutralizing antibody levels were not affected, the number of IFN-γ-secreting cells was increased after BoHV-1 challenge, specifically the CD8+ IFN-γ+ T cells, including CD8+ IFN-γ+ CD25+ CTLs. While reduced virus shedding, rectal temperature, and weight loss were observed, the level of protection was comparable to that observed in pMASIA-tgD-vaccinated animals. These data show that coadministration of BNBD3 with a protective antigen as a fusion in a DNA vaccine strengthened the Th1 bias and increased cell-mediated immune responses but did not enhance protection from BoHV-1 infection. PMID:24451331

  18. [Conversion of 17 alpha-methyltestosterone to methandrostenolone by the bacterium Pimelobacter simplex VKPM Ac-1632 with the presence of cyclodextrins].

    PubMed

    Druzhinina, A V; Andriushina, V A; Stytsenko, T S; Voĭshvillo, N E

    2008-01-01

    Conditions of conversion of 17 alpha-methyltestosterone to methandrostenolone with the presence of modified beta-cyclodextrins (methylcyclodextrin, hydroxypropylcyclodextrin, and hydroxyethylcyclodextrin) in the steroid:cyclodextrin ratio 1:1 were studied. The experimental solutions of modified beta-cyclodextrins were prepared in deionized water with 5-7% methanol. Under the conditions found to be optimal, 1,2-dehydrogenation of 17 alpha-methyltestosterone was carried out with 2-4 g/l Pimelobacter simplex VKPM Ac-1632 biomass. At the substrate concentration 5-20 g/l, the reaction occurred for 1-15 h without any by-products. The maximum rate of methandrostenolone accumulation was observed with hydroxypropylcyclodextrin. The methylcyclodextrin solution can be reused for complete 17 alpha-methyltestosterone conversion at the concentration 5 g/l. PMID:19145970

  19. State-of-the-art applications of cyclodextrins as functional monomers in molecular imprinting techniques: a review.

    PubMed

    Lay, Sovichea; Ni, Xiaofeng; Yu, Haining; Shen, Shengrong

    2016-06-01

    As a versatile tool in separation science, cyclodextrins and their derivatives, known as emerging functional monomers, have been used extensively in molecular imprinting techniques. The attributes of cyclodextrins and their derivatives are widely known to form host-guest inclusion complex processes between the polymer and template. The exploitation of the imprinting technique could produce a product of molecularly imprinted polymers, which are very robust with long-term stability, reliability, cost-efficiency, and selectivity. Hence, molecularly imprinted polymers have gained popularity in chemical separation and analysis. Molecularly imprinted polymers containing either cyclodextrin or its derivatives demonstrate superior binding effects for a target molecule. As noted in the previous studies, the functional monomers of cyclodextrins and their derivatives have been used in molecular imprinting for selective separation with a wide range of chemical compounds, including steroidals, amino acids, polysaccharides, drugs, plant hormones, proteins, pesticides, and plastic additives. Therefore, the main goal of this review is to illustrate the exotic applications of imprinting techniques employing cyclodextrins and their derivatives as single or binary functional monomers in synthesizing molecularly imprinted polymers in areas of separation science by reviewing some of the latest studies reported in the literature. PMID:27324352

  20. Dehydration, dissolution, and melting of cyclodextrin crystals.

    PubMed

    Specogna, Erika; Li, King Wo; Djabourov, Madeleine; Carn, Florent; Bouchemal, Kawthar

    2015-01-29

    Cyclodextrins are a family of oligosaccharides with a toroid shape that exhibit a unique ability of entrapping guest molecules in their internal cavity. Water is the primary guest molecule and is omnipresent in the crystalline phases stabilizing the overall architecture. Despite the presence of water molecules inside the cavity, cyclodextrins provide a hydrophobic environment where poorly soluble molecules can easily fit. In this investigation we put in evidence different types of water in the hydrated α-, β-, and γ-cyclodextrin crystals. Thermogravimetric measurements identify various binding sites of water and highlight the difference between the crystals equilibrated under various humid atmospheres. We establish by microcalorimetry the limit of solubility versus temperature and measure for the first time the melting temperatures of the hydrated crystals. Dissolution and melting enthalpies are derived and the solubility curves are compared to existing literature. The specific features of each cyclodextrin are underlined. PMID:25565266

  1. Retention of aroma compounds from Mentha piperita essential oil by cyclodextrins and crosslinked cyclodextrin polymers.

    PubMed

    Ciobanu, A; Mallard, I; Landy, D; Brabie, G; Nistor, D; Fourmentin, S

    2013-05-01

    In this paper, the controlled release of aroma compounds from cyclodextrins (CDs) and CD polymers was studied by multiple headspace extraction (MHE) experiments. Mentha piperita essential oil was obtained by Soxhlet extraction and identification of the major compounds was performed by GC-MS analysis. Menthol, menthone, pulegone and eucalyptol were identified as the major components. Retention of standard compounds in the presence of different CDs and CD polymers has been realised by static headspace gas chromatography (SH-GC) at 25 °C in the aqueous or gaseous phase. Stability constants for standard compounds and for compounds in essential oil have been also determined with monomeric CD derivatives. The obtained results indicated the formation of a 1:1 inclusion complex for all the studied compounds. Molecular modelling was used to investigate the complementarities between host and guest. This study showed that β-CDs were the most versatile CDs and that β-CD polymers could perform the controlled release of aroma compounds. PMID:23265490

  2. Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

    PubMed Central

    Nardello-Rataj, Véronique

    2014-01-01

    Summary Host–guest chemistry is useful for the construction of nanosized objects. Some of the widely used hosts are probably the cyclodextrins (CDs). CDs can form water-soluble complexes with numerous hydrophobic compounds. They have been widespread used in medicine, drug delivery and are of interest for the biocides encapsulation. Indeed, this enables the development of more or less complex systems that release antimicrobial agents with time. In this paper, the general features of CDs and their applications in the field of biocides have been reviewed. As the key point is the formation of biocide–CD inclusion complexes, this review deals with this in depth and the advantages of biocide encapsulation are highlighted throughout several examples from the literature. Finally, some future directions of investigation have been proposed. We hope that scientists studying biocide applications receive inspiration from this review to exploit the opportunities offered by CDs in their respective research areas. PMID:25550722

  3. Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens.

    PubMed

    Nardello-Rataj, Véronique; Leclercq, Loïc

    2014-01-01

    Host-guest chemistry is useful for the construction of nanosized objects. Some of the widely used hosts are probably the cyclodextrins (CDs). CDs can form water-soluble complexes with numerous hydrophobic compounds. They have been widespread used in medicine, drug delivery and are of interest for the biocides encapsulation. Indeed, this enables the development of more or less complex systems that release antimicrobial agents with time. In this paper, the general features of CDs and their applications in the field of biocides have been reviewed. As the key point is the formation of biocide-CD inclusion complexes, this review deals with this in depth and the advantages of biocide encapsulation are highlighted throughout several examples from the literature. Finally, some future directions of investigation have been proposed. We hope that scientists studying biocide applications receive inspiration from this review to exploit the opportunities offered by CDs in their respective research areas. PMID:25550722

  4. Complexation of quercetin with three kinds of cyclodextrins: An antioxidant study

    NASA Astrophysics Data System (ADS)

    Jullian, Carolina; Moyano, Lorena; Yañez, Claudia; Olea-Azar, Claudio

    2007-05-01

    The slightly water-soluble flavonoid quercetin (QUE) and its inclusion with either β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HP-βCD) or sulfobutyl ether-β-cyclodextrin (SBE-βCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility measurements; in all cases type-A L diagrams have been obtained (soluble 1:1 complexes). The results showed that the inclusion ability of βCD and its derivatives was the order: SBE-βCD > HP-βCD > βCD. Kinetic studies of DPPH rad with QUE and CDs complexes were done. The results obtained indicated that the QUE-SBE-βCD complex was the most reactive form. The scavenging capability of QUE and CDs complexes with DPPH rad and galvinoxyl was studied using ESR spectroscopy. All complexes showed a higher scavenging capability with both radicals, compare quercetin in water. Beside, these results indicated that the complexes formed maintained the quercetin antioxidant activity.

  5. Studies on the complexation of diclofenac sodium with β-cyclodextrin: Influence of method of preparation

    NASA Astrophysics Data System (ADS)

    Das, Subhraseema; Subuddhi, Usharani

    2015-11-01

    Inclusion complexes of diclofenac sodium (DS) with β-cyclodextrin (β-CD) were prepared in order to improve the solubility, dissolution and oral bioavailability of the poorly water soluble drug. The effect of method of preparation of the DS/β-CD inclusion complexes (ICs) was investigated. The ICs were prepared by microwave irradiation and also by the conventional methods of kneading, co-precipitation and freeze drying. Though freeze drying method is usually referred to as the gold standard among all the conventional methods, its long processing time limits the utility. Microwave irradiation accomplishes the process in a very short span of time and is a more environmentally benign method. Better efficacy of the microwaved inclusion product (MW) was observed in terms of dissolution, antimicrobial activity and antibiofilm properties of the drug. Thus microwave irradiation can be utilized as an improved, time-saving and cost-effective method for the generation of DS/β-CD inclusion complexes.

  6. Effect of cyclodextrin derivation and amorphous state of complex on accelerated degradation of ziprasidone.

    PubMed

    Hong, Jinyang; Shah, Jaymin C; Mcgonagle, Maura D

    2011-07-01

    Inclusion complexes of ziprasidone with several β-cyclodextrins [β-CDs; sulfobutylether-β-cyclodextrins (SBEβCD), hydroxypropyl-β-cyclodextrins (HPβCD), methyl-β-cyclodextrins (MβCD), and carboxyethyl-β-cyclodextrins (CEβCD)] were prepared and solution stability was evaluated at elevated temperature. Solid-state stability was assessed by subjecting various CD complexes of ziprasidone, spray-dried dispersion (SDD), partially crystalline ziprasidone-SBEβCD salts, and the physical mixture of ziprasidone-SBEβCD to γ-irradiation. Degradant I was formed by oxidation of ziprasidone, which upon aldol condensation with ziprasidone formed degradant II in both solution and solid states. In the solution state, CD complexes with electron-donating side chains, such as SBEβCD and CEβCD, produced the highest oxidative degradation followed by HPβCD with 6, 3, and 4 degrees of substitution. In the solid state, crystalline drug substance and physical mixture of crystalline drug-SBEβCD showed very little to no degradation. In contrast, amorphous βCD, MβCD, CEβCD, and SBEβCD complexes as well as the amorphous SDD exhibited greatest extent of oxidative degradation. Results suggest that electron-donating side chains of the derivatized CD interact with transition state of the oxidation reaction and catalyze drug degradation in solution, However, higher mobility in the amorphous state of CD-drug complexes promoted chemical instability of ziprasidone under accelerated conditions irrespective of the chemical nature of the side chain on CD. PMID:21283987

  7. Inclusion Kinetics of Polyrotaxanes

    NASA Astrophysics Data System (ADS)

    Yokoyama, Hideaki; Takahashi, Shoko; Ito, Kohzo; Yamada, Norifumi

    Inclusion complex (IC) formation of α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG) brush in water was investigated by Surface Plasmon Resonance Spectroscopy(SPR), neutron reflectometry(NR) and grazing incident wide angle X-ray scattering(GISANS). Spontaneous IC formation of α-CD with PEG (polyrotaxanes) is believed to be due to hydrophobic interaction between the hydrophobic interior of α-CD and PEG; however, the detail of the IC formation kinetics has not been observed because IC formation results in aggregation and precipitation of the complex. SPR revealed that IC formation occurs after induction period, which often appears in crystallization. When concentration of α-CD solution is 10%, IC consisting randomly oriented α-CD polycrystal appeared. In contrast, when the concentration of α-CD solution is 5%, a uniform 10-nm-thick IC layer with α-CD stacked perpendicular to the substrate appeared. 10-nm-thick IC was also found in the diluted PEG brush in contact with a 10% α-CD solution. The characteristic 10-nm-thick layer is related to the folded crystalline structure of α-CD on PEG brush. Such crystallization was proved to be the main driving force for IC formation.

  8. Characterization and cytocompatibility of an antibiotic/chitosan/cyclodextrins nanocoating on titanium implants.

    PubMed

    Mattioli-Belmonte, Monica; Cometa, Stefania; Ferretti, Concetta; Iatta, Roberta; Trapani, Adriana; Ceci, Edmondo; Falconi, Mirella; De Giglio, Elvira

    2014-09-22

    A novel ciprofloxacin loaded chitosan nanoparticle-based coating onto titanium substrates has been developed and characterized to obtain an orthopaedic implant surface able to in situ release the antibiotic for the prevention of post-operative infections. Ciprofloxacin loaded chitosan nanoparticles were obtained using the combination of sulfobutyl ether-beta-cyclodextrin and gamma-cyclodextrin. The resulting nanoparticulate system was characterized by TEM, HPLC and XPS. Particle size was in the range 426-552 nm and zeta potential values were around +30 mV. This antibacterial coating was able to in vitro inhibit two nosocomial Staphylococcus aureus strains growth, with a reduction of about 20 times compared to controls. No impairment in MG63 osteoblast-like cells viability, adhesion and gene expression were detected at 48 h, 7 and 14 days of culture. Overall, the investigated coating represents a promising candidate for the development of a new antibiotic carrier for titanium implants. PMID:24906744

  9. Investigating 2,2'-bipyridine-3,3'-diol as a microenvironment-sensitive probe: its binding to cyclodextrins and human serum albumin.

    PubMed

    Abou-Zied, Osama K

    2007-08-23

    The 2,2'-bipyridine-3,3'-diol molecule (BP(OH)2) was investigated as a potential photophysical probe in inclusion and biological studies. Binding of BP(OH)2 to cyclodextrins (CDs) and human serum albumin (HSA) was studied by following the changes in its absorption and fluorescence spectra. The stoichiometric ratios and binding constants of the complexes were deduced by fitting the changes in the spectral intensity to binding isotherms. The stoichiometric ratio in the BP(OH)2/(alpha-CD) complex is dominated by 1:2, whereas in all other CDs and in HSA this ratio is 1:1. The structure of the BP(OH)2:(alpha-CD)2 complex, calculated using ab initio methods, indicates that the inclusion of the BP(OH)2 molecule is axial and centered between the two cavities of alpha-CD with van der Waals and electrostatic interactions dominating the binding. Analysis of these results along with the inclusion results of BP(OH)2 in beta-CD, methyl-beta-CD, 2,6-di-O-methyl-beta-CD, and gamma-CD shows that absorption and fluorescence of BP(OH)2 are very sensitive to the change in the cavity size of CD and its hydrophobicity. This change is reflected in the form of a decrease in the intensity of the absorption peaks of the BP(OH)2/water complex in the region 400-450 nm and a red shift in the fluorescence peak as the cavity size decreases and its hydrophobicity increases. Binding of BP(OH)2 as a probe ligand to HSA, a prototype protein, reflects the hydrophobic interior of HSA in a similar manner. The spectral changes indicate that BP(OH)2 binds in the hydrophobic cavity of HSA's subdomain IIA. The results presented here show that BP(OH)2 can be used in binding sites and biological systems as a microenvironment-sensitive probe. PMID:17655352

  10. Caging and solvent effects on the tautomeric equilibrium of 3-pyridone/3-hydroxypyridine in the ground state: a study in cyclodextrins and binary solvents.

    PubMed

    Abou-Zied, Osama K; Al-Shihi, Othman I K

    2009-07-14

    The tautomeric equilibrium between 3-pyridone (3Py) and 3-hydroxypyridine (3HP) shows characteristic absorption peaks for the zwitterion form of 3Py in water that may be used as a probe of the hydrophobic nature inside macromolecules such as proteins and other biologically related systems. We studied this equilibrium in the ground state in aqueous cyclodextrins (CDs) and in binary solvent mixtures of 1,4-dioxane and water by absorption spectroscopy, and by ab initio calculations. Upon the addition of alpha-CD or beta-CD to an aqueous solution of the 3Py/3HP system, the absorbance intensity of the zwitterion tautomer decreases with a concomitant increase in the intensity of the enol tautomer of 3HP. The results reflect the nature of the tautomeric equilibrium and point to the hydrophobic environment inside the CD cavities. The effect of inclusion is noticeably less in the case of alpha-CD. This is attributed to the small cavity size of alpha-CD which sustains only partial inclusion. Upon the addition of gamma-CD, the intensity of the zwitterion tautomer slightly increased over that in water which is attributed to the direct interaction between the charged sides of the tautomer with the outer primary or secondary hydroxyls of the glycopyranose units of gamma-CD. This interaction is a result of the large cavity size of gamma-CD which does not support a stable complex. The largest caging effect was observed in 2,6-di-O-methyl-beta-CD (DMbeta-CD) which is an indication of a more hydrophobic environment around the guest. The large hydrophobicity of DMbeta-CD is due to the presence of the two methyl groups in the beta-CD derivative which reduce the amount of water inside the cavity upon encapsulation. In the binary mixtures of 1,4-dioxane and water, the change in the absorbance intensity of the enol and the zwitterion tautomers was analyzed quantitatively and three water molecules were found to solvate the polar centers of each tautomer. Ab initio calculations of the

  11. Inclusive health.

    PubMed

    Maclachlan, Malcolm; Khasnabis, Chapal; Mannan, Hasheem

    2012-01-01

    We propose the concept of Inclusive Health to encapsulate the Health for All ethos; to build on the rights-based approach to health; to promote the idea of inclusion as a verb, where a more proactive approach to addressing distinctive and different barriers to inclusion is needed; and to recognise that new initiatives in human resources for health can offer exciting and innovative ways of healthcare delivery. While Inclusive Education has become a widely recognised and accepted concept, Health for All is still contested, and new thinking is required to develop its agenda in line with contemporary developments. Inclusive Health refers both to who gets health care and to who provides it; and its ethos resonates strongly with Jefferson's assertion that 'there is nothing more unequal, than the equal treatment of unequal people'. We situate the timeliness of the Inclusive Health concept with reference to recent developments in the recognition of the rights of people with disability, in the new guidelines for community-based rehabilitation and in the World Report on Disability. These developments offer a more inclusive approach to health and, more broadly, its inter-connected aspects of wellbeing. A concept which more proactively integrates United Nations conventions that recognise the importance of difference - disability, ethnicity, gender, children - could be of benefit for global healthcare policy and practice. PMID:21895893

  12. Inclusive teaching.

    PubMed

    Billings, Diane M

    2008-07-01

    Inclusive teaching involves being responsive to the diversity represented in the classroom and assisting learners to focus on their culture, attitudes, and beliefs while learning to communicate and collaborate with each other and their patients. PMID:18649804

  13. Solid-state hierarchical cyclodextrin-based supramolecular polymer constructed by primary, secondary, and tertiary azido interactions.

    PubMed

    Ménand, Mickaël; Adam de Beaumais, Ségolène; Chamoreau, Lise-Marie; Derat, Etienne; Blanchard, Sébastien; Zhang, Yongmin; Bouteiller, Laurent; Sollogoub, Matthieu

    2014-07-01

    The crystallization of a di-azido-α-cyclodextrin revealed a polymeric self-assembly involving a variety of azido-type interactions. The crystal arrangement relies on the cooperativity of a primary azido inclusion, a secondary azido-azido interaction involving an unprecedented distribution of canonical forms, and a tertiary azido-groove interaction. The second azido group brings in a major contribution to the supramolecular structure illustrating the benefit of a difunctionalization for the generation of hierarchy. PMID:24866704

  14. Structural investigation of the β-cyclodextrin complexes with linalool and isopinocampheol - Influence of monoterpenes cyclicity on the host-guest stoichiometry

    NASA Astrophysics Data System (ADS)

    Ceborska, Magdalena

    2016-05-01

    The crystal structures of the complexes of β-cyclodextrin with two chiral terpene alcohols are presented. (-)-Linalool forms the complex of a 2:2 host-guest stoichiometry, while the complex with (-)-isopinocampheol exhibits a 2:3 stoichiometry. The comparison of the crystal structures with the data for other complexes of β-cyclodextrin with chiral monoterpene alcohols obtained from Cambridge Structural Database (CSD) highlights the tendency of linear and monocyclic alcohols to form complexes of 2:2 stoichiometry whereas bicyclic alcohols prefer to form 2:3 host-guest inclusion complexes.

  15. Cyclodextrin-Based Solid-Gas Clathrates.

    PubMed

    Pereva, Stiliana; Himitliiska, Tsveta; Spassov, Tony; Stoyanov, Simeon D; Arnaudov, Luben N; Dudev, Todor

    2015-07-29

    "Cyclodextrin-gas" clathrates were obtained by crystallization from water solution of α-, β-, and γ-cyclodextrins (CDs) under pressure of the gas to be entrapped into the CD molecules. When the pressure is released, these clathrates are stable at ambient conditions and dissociate at elevated temperature, which makes them interesting for various applications as foam boosters in food and other industries. It was found that under these conditions α-CD forms clathrates with all of the gases used in this study (N2, N2O, CO2, Ar), whereas β- and γ-CDs can form clathrates only with N2. The concentration of the cyclodextrin and the temperature and pressure of the gas were varied for achieving higher clathrate yield and larger amount of embedded gas. Highest values of about 2 wt % were found for α-CD-N2O, as it releases in the temperature range of 40-60 °C. PMID:26132981

  16. Physicochemical characterization of 2-hydroxybenzophenone with β-cyclodextrin in solution and solid state.

    PubMed

    Sancho, Matias I; Russo, Marcos G; Moreno, M Sergio; Gasull, Estela; Blanco, Sonia E; Narda, Griselda E

    2015-05-01

    The characterization of the inclusion complex between 2-hydroxybenzophenone (2OHBP) and β-cyclodextrin (βCD) in the solid state was performed using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). The apparent formation constant of the complex was determined by phase solubility diagrams and liquid chromatography (HPLC) at different temperatures. T