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Sample records for beta cyclodextrin inclusion

  1. [Spectrofluorimetric study of supramolecular inclusion between rodenticide brodifacoum and beta-cyclodextrin and application].

    PubMed

    Duan, Yun-Qing; Duan, Zhi-Qing; Min, Shun-Geng; Xiong, Yan-Mei; Duan, Jia; Ye, Sheng-Feng; Wang, Dong

    2010-04-01

    The supramolecular interaction between beta-cyclodextrin and brodifacoum, an anticoagulant rodenticide of the second generation, was studied by spectroscopy. The results showed that brodifacoum and beta-cyclodextrin could form an inclusion complex with an association constant of 1.048 x 10(4) L x mol(-1) and a 1 : 1 stoichiometry based on Benesi-Hildebrand equation. The inclusion mechanism was proposed to explain the inclusion mode. It was indicated that the hydrophobic group of brodifacoum molecule, biphenyl, entered into the cavity of beta-cyclodextrin. At the same time, it was also observed the significant enhancement of fluorescence of brodifacoum after forming inclusion complex. According to the fluorescence enhancement phenomenon, a spectrofluorimetric method of detecting brodifacoum in aqueous media was established with the linear range of 8.0 x 10(-8)-4.0 x 10(-6) mol x L(-1) and the correlation coefficient of 0.999 4. The detection limit of the method was 8.8 x 10(-9) mol x L(-1). The proposed method was successfully applied to determine the trace amount of brodifacoum in environment water and the recovery was in the range of 87.3% to 103.9%.

  2. 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.

  3. Characterization of aqueous and solid inclusion complexes of diuron and isoproturon with beta-cyclodextrin.

    PubMed

    Dupuy, N; Marquis, S; Vanhove, G; Bria, M; Kister, J; Vrielynck, L

    2004-06-01

    The interaction of diuron and isoproturon herbicides with beta-cyclodextrin is conducive to the formation of inclusion compounds in aqueous solution as well as in the solid state. The physico-chemical study of these complexes was carried out by various analytical techniques such as ultraviolet (UV), Fourier transform infrared (FT-IR), Raman, X-ray diffraction, and 1H-NMR (nuclear magnetic resonance) spectroscopies. The existence of inclusion complexes in water solution between the beta-cyclodextrin and each of the herbicides was revealed by electronic absorption and 1H-NMR spectroscopies. A 1:1 stoichiometry was determined for both complexes in aqueous medium from UV absorption spectra by using the Benesi-Hildebrand method; the relative stability constants at room temperature were calculated at 2700 +/- 300 L mol(-1) and 750 +/- 50 L mol(-1) for isoproturon and diuron, respectively. In the solid state, inclusion processes with beta-cyclodextrin were characterized by means of infrared and Raman techniques and confirmed by X-ray diffraction spectra.

  4. Physico-chemical characterization of benzocaine-beta-cyclodextrin inclusion complexes.

    PubMed

    Pinto, Luciana M A; Fraceto, Leonardo Fernandes; Santana, Maria Helena A; Pertinhez, Thelma A; Junior, Sérgio Oyama; de Paula, Eneida

    2005-10-04

    Local anesthetics are able to induce pain relief by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of the nervous impulse. Benzocaine (BZC) is a local anesthetic whose low water-solubility limits its application to topical formulations. The present work focuses on the characterization of inclusion complexes of BZC in beta-cyclodextrin (beta-CD). Differential scanning calorimetry and electron microscopy gave evidences of the formation and the morphology of the complex. Fluorescence spectroscopy showed a BZC/beta-CD 1:1 stoichiometry. Phase-solubility diagrams allowed the determination of the association constants between BZC and beta-CD (549 M(-1)) and revealed that a three-fold increase in BZC solubility can be reached upon complexation with beta-CD. The details of BZC/beta-CD molecular interaction were analyzed by 1H 2D NMR allowing the proposition of an inclusion model for BZC into beta-CD where the aromatic ring of the anesthetic is located near the head of the beta-CD cavity. Moreover, in preliminary toxicity studies, the complex seems to be less toxic than BZC alone, since it induced a decrease in the in vitro oxidation of human hemoglobin. These results suggest that the BZC/beta-CD complex represents an effective novel formulation to enhance BZC solubility in water, turning it promising for use outside its traditional application, i.e., in infiltrative anesthesia.

  5. Investigation of the inclusions of puerarin and daidzin with beta-cyclodextrin by molecular dynamics simulation.

    PubMed

    Zhang, Haiyang; Feng, Wei; Li, Cong; Tan, Tianwei

    2010-04-15

    Puerarin and daidzin, two major isoflavonoids of Radix puerariae , are widely adopted in traditional Chinese medicine. Foundational aspects related to separating the two compounds are essential to develop a more economical purification process. Inclusion models of the two compounds with beta-cyclodextrin (beta-CD) have been investigated by molecular dynamics simulation. Computational results reveal that both puerarin and daidzin can induce a conformational change of beta-CD, which is compressed in one direction and stretched in the other. The effect of solvent and media on the conformational change of beta-CD and the movement of guest molecules inside the cavity has been investigated. Furthermore, hydrogen bonding interactions have been analyzed, and the results have been utilized for the explanation of separating puerarin from daidzin.

  6. Study of inclusion complex formation between tropaeolin OO and beta-cyclodextrin by spectrophotometry and Infrared spectroscopy.

    PubMed

    Wang, Huai You; Han, Juan; Feng, Xia Guang; Pang, Yan Ling

    2006-09-01

    The mechanism of the inclusion of tropaeolin OO (TPOO) and beta-cyclodextrin (beta-CD) has been studied by spectrophotometry. The inclusion depth of the guest molecule in the host molecule was demonstrated by infrared spectrometry. Effect of the pH, concentrations of beta-CD, solvents and ionic strength on the inclusion of TPOO and beta-CD were examined. The result showed that TPOO reacts with beta-CD to form a 1:1 host-guest complex with an apparent formation constant of 1.50 x 10(3) l mol(-1). The thermodynamic parameters of inclusion reaction, DeltaG degrees , DeltaH degrees and DeltaS degrees were obtained.

  7. 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.

  8. 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.

  9. Curve-fitting FTIR studies of loratadine/hydroxypropyl-beta-cyclodextrin inclusion complex induced by co-grinding process.

    PubMed

    Lin, Shan-Yang; Hsu, Cheng-Hung; Sheu, Ming-Thau

    2010-11-02

    The formation steps of inclusion complex caused by co-grinding loratadine (LOR) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a molar ratio of 1:1 or 1:2 were quantitatively investigated by Fourier transform infrared (FTIR) spectroscopy with curve-fitting analysis and differential scanning calorimetry (DSC). The phase solubility study and the co-evaporated solid products of the mixture of LOR and HP-beta-CD were also examined. The result indicates that the aqueous solubility of LOR was linearly increased with the increase of HP-beta-CD concentrations, in which the phase solubility diagram was classified as A(L) type. The higher apparent stability constant (2.22 x 10(4)M(-1)) reveals that the inclusion complex formed between LOR and HP-beta-CD was quite stable. The endothermic peak at 134.6 degrees C for the melting point of LOR gradually disappeared from DSC curves of LOR/HP-beta-CD coground mixtures by increasing the cogrinding time, as the disappearance of the co-evaporated solid products. The disappearance of this endothermic peak from LOR/HP-beta-CD coground mixture or the co-evaporated solid products was due to the inclusion complex formation between LOR and HP-beta-CD after cogrinding process or evaporation. Moreover, IR peaks at 1676 cm(-1) down-shifted from 1703 cm(-1) (CO stretching) and at 1235 cm(-1) upper-shifted from 1227 cm(-1) (C-O stretching) related to LOR in the inclusion complex were observed with the increase of cogrinding time, but the peak at 1646 cm(-1) due to O-H stretching of HP-beta-CD was shifted to 1640 cm(-1). The IR spectrum of 15 min-coground mixture was the same as the IR spectrum of the co-evaporated solid product, strongly indicating that the grinding process could cause the inclusion complex formation between LOR and HP-beta-CD. Three components (1700, 1676, and 1640 cm(-1)) and their compositions were certainly obtained in the 1740-1600 cm(-1) region of FTIR spectra for the LOR/HP-beta-CD coground mixture and the co

  10. [In-vitro evaluation of cinnarizine as a competing agent to beta-cyclodextrin inclusion complexes: effect of cinnarizine on the membrane permeation rate of progesterone from its beta-cyclodextrin inclusion complex].

    PubMed

    Muraoka, Atsushi; Tokumura, Tadakazu; Machida, Yoshiharu

    2008-01-01

    The use of competing agents is considered a powerful tool for the development of a drug-delivery system with drug/cyclodextrin inclusion complexes. However, there are very few studies examining this issue. To explain this phenomenon, it was thought that a competing agent with a sufficiently high stability constant had not yet been reported. In this study, cinnarizine (CN), which has a high stability constant with beta-cyclodextrin (beta-CD) and unique solubility characteristics, was selected, and its ability as a competing agent was examined in a membrane permeability study. The permeability study showed that the permeation rates of the drugs flurbiprofen, progesterone, and spironolactone decreased with their stability constants with the addition of beta-CD. In one of the drugs, progesterone (Pro), the decrease was restored by the addition of CN. The amount of CN added was a 1:1 molar ratio to the amount of Pro. However, no similar action was induced with the addition of DL-phenylalanine (Phe) in the permeation study at the 1:5 (Pro:Phe) molar ratio. These finding indicate that CN acts as a competing agent, and its action is much stronger than that of Phe.

  11. Imazalil-cyclomaltoheptaose (beta-cyclodextrin) inclusion complex: preparation by supercritical carbon dioxide and 13C CPMAS and 1H NMR characterization.

    PubMed

    Lai, Simona; Locci, Emanuela; Piras, Alessandra; Porcedda, Silvia; Lai, Adolfo; Marongiu, Bruno

    2003-10-10

    An inclusion complex between imazalil (IMZ), a selected fungicide, and cyclomaltoheptaose (beta-cyclodextrin, betaCD) was obtained using supercritical fluid carbon dioxide. The best preparation conditions were determined, and the inclusion complex was investigated by means of 1H NMR spectroscopy in aqueous solution and 13C CPMAS NMR spectroscopy in the solid state. Information on the geometry of the betaCD/IMZ complex was obtained from ROESY spectroscopy, while the dynamics of the inclusion complex in the kilohertz range was obtained from the proton spin-lattice relaxation times in the rotating frame, T(1rho) (1H).

  12. UV-vis and FTIR-ATR characterization of 9-fluorenon-2-carboxyester/(2-hydroxypropyl)-beta-cyclodextrin inclusion complex.

    PubMed

    Stancanelli, R; Ficarra, R; Cannavà, C; Guardo, M; Calabrò, M L; Ficarra, P; Ottanà, R; Maccari, R; Crupi, V; Majolino, D; Venuti, V

    2008-08-05

    In this work, the usefulness of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) as a tool to form an inclusion complex with 9-fluorenonic derivative (AG11) has been investigated, in pure water, by UV absorption. Phase-solubility diagrams allowed the determination of the association constant between AG11 and HP-beta-CyD. At the same time, solid binary systems between AG11 and HP-beta-CyD have been prepared in 1:1 stoichiometry by co-precipitation method. In order to confirm the complexation, FTIR spectroscopy in ATR geometry measurements have been performed and the results have been compared with the free compounds and the corresponding physical mixture in the same molar ratio. The nature of the interactions between AG11 and HP-beta-CyD has been elucidated also by applying mathematical procedures such as deconvolution and curve fitting. Improvement of the aqueous solubility is expected to improve the bioavailability of the drug in oral administration.

  13. Improvement of oral bioavailability of flurbiprofen from flurbiprofen/beta-cyclodextrin inclusion complex by action of cinnarizine.

    PubMed

    Tokumura, Tadakazu; Muraoka, Atsushi; Machida, Yoshiharu

    2009-09-01

    Improvement of the oral bioavailability of flurbiprofen (Flu) after oral administration of flurbiprofen/beta-cyclodextrin inclusion complex (Flu/beta-CD) by the action of cinnarizine (CN) was investigated. Flu and Flu/beta-CD were administered orally to fasted rats at a dose of 20mg/kg as Flu. Thirty minutes after drug administration, CN dissolved in pH 4.0 buffer solution or pH 4.0 buffer solution alone was administered to the rats. The dose of CN was 0.17 mg/kg. Blood samples were taken from rats and Flu concentrations in plasma samples were determined by HPLC. It was found from the comparison of Flu and Flu with CN (Flu+CN) that CN had no effect on plasma concentrations of Flu after oral administration of Flu. The mean plasma levels after oral administration of Flu/beta-CD with CN (Flu/beta-CD+CN) were larger not only than those of Flu and Flu+CN but also than those of Flu/beta-CD. The value of C(max) in Flu/beta-CD+CN was significantly larger than that of Flu/beta-CD. This is considered to be caused by the action of CN as a competing agent. This mechanism was supported by the result of solubility study in which Flu solubility in beta-CD solution decreased with the addition of CN. It was found from these results that CN had strong ability as a competing agent in vivo.

  14. Analysis of the phase solubility diagram of a phenacetin/competitor/beta-cyclodextrin ternary system, involving competitive inclusion complexation.

    PubMed

    Ono, N; Hirayama, F; Arima, H; Uekama, K

    2001-01-01

    The competitive inclusion complexations in the ternary phenacetin/competitors/beta-cyclodextrin (beta-CyD) systems were investigated by the solubility method, where m-bromobenzoic acid (m-BBA) and o-toluic acid (o-TA) were used as competitors. The solubility changes of the drug and competitors as a function of beta-CyD concentration in the ternary systems were formulated using their stability constants and intrinsic solubilities. The decrease in solubility of phenacetin by the addition of competitors could be quantitatively simulated by the formulation, when both drug and competitor give A(L) type solubility diagrams. On the other hand, when one of the guests gives a B(S) type solubility diagram, its solubility change was clearly reflected in that of the another guest, i.e., phenacetin gave an A(L) type solubility diagram in the binary phenacetin/beta-CyD system and o-TA gave a B(S) type diagram in the binary o-TA/beta-CyD system, but in the ternary phenacetin/o-TA/beta-CyD system, a new plateau region appeared in the original A(L) type diagram of phenacetin. This was explained by the solubilization theory of Higuchi and Connors. The solubility analysis of the ternary drug/competitor/CyD systems may be particularly useful for determination of the stability constant of a drug whose physicochemical and spectroscopic analyses are difficult, because they can be calculated by monitoring the solubility change of a competitor, without monitoring that of a drug. Furthermore, the present results suggest that attention should be paid to the type of the phase solubility diagram, as well as the magnitude of the stability constant and the solubility of the complex, for a rational formulation design of CyD complexes.

  15. Inclusion complexation behavior of dyestuff guest molecules by a bridged bis(cyclomaltoheptaose)[bis(beta-cyclodextrin)] with a pyromellitic acid diamide tether.

    PubMed

    Liu, Yu; Li, Li; Zhang, Heng-Yi; Liang, Peng; Wang, Hao

    2003-08-12

    A novel bridged bis(beta-cyclodextrin) with a pyromellitic acid 2,5-diamide tether (2) has been synthesized by reaction of 6(I)-(2-aminoethyleneamino)-6-deoxycyclomaltoheptaose [mono 6-(2-aminoethyleneamino)-6-deoxy-beta-cyclodextrin] with 1,2,4,5-benzenetetracarboxylic dianhydride. Its inclusion complexation behavior with some representative dyestuffs, i.e., Acridine Red (AR), Rhodamine B (RhB), Neutral Red (NR), Brilliant Green (BG), was studied by using UV-absorption, fluorescence, and 2D NMR spectroscopy. Fluorescence titrations have been performed at 25 degrees C in pH 7.2 buffer solution to calculate the binding constants of resulting complexes. These results obtained indicated that bis(beta-cyclodextrin) 2 exhibits the strongly enhanced binding ability with all dye molecules examined compared with natural cyclodextrins. The binding modes of 2 with dye molecules have been deduced by 2D NMR experiments to establish the correlations between molecular conformations and binding constants of inclusion complexation. It is found that the improved binding ability and molecular selectivity of 2 could be attributed to double-cavity cooperative inclusion interaction and the size/shape matching between the host and guest.

  16. 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.

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

    PubMed

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

    2014-01-03

    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.

  18. Tumor-specific cytotoxicity and type of cell death induced by beta-cyclodextrin benzaldehyde inclusion compound.

    PubMed

    Liu, Yu; Sakagami, Hiroshi; Hashimoto, Ken; Kikuchi, Hirotaka; Amano, Osamu; Ishihara, Mariko; Kanda, Yumiko; Kunii, Shiro; Kochi, Mutsuyuki; Zhang, Wei; Yu, Guangyan

    2008-01-01

    The cytotoxicity of beta-cyclodextrin benzaldehyde inclusion compound (CDBA) against human normal and cancer cell lines was investigated. CDBA showed slightly higher cytotoxicity against human tumor cell lines, as compared to normal cells, with a tumor-specificity index of 2.2. Human myelogenous leukemia cell lines (HL-60, ML-1, KG-1) were the most sensitive to CDBA, followed by human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4) and human glioblastoma (T98G, U87MG). Human normal cells (gingival fibroblasts, pulp cells, periodontal ligament fibroblasts) were the most resistant. CDBA induced internucleosomal DNA fragmentation in HL-60 cells and caspase-3, -8, -9 activation, but to a much lesser extent than that attained by UV irradiation or actinomycin D. On the other hand, CDBA did not induce DNA fragmentation, nor caspase activation in HSC-2, HSC-4 or T98G cells. Electron microscopy demonstrated that CDBA induced the destruction of mitochondrial structure and digestion of broken organelles by secondary lysosomes in all of these cells. CDBA also increased the number of acidic organelles as judged by acridine orange staining. The present study suggests that CDBA induces autophagic cell death in cancer cell lines.

  19. 13C-CPMAS and 1H-NMR study of the inclusion complexes of beta-cyclodextrin with carvacrol, thymol, and eugenol prepared in supercritical carbon dioxide.

    PubMed

    Locci, Emanuela; Lai, Simona; Piras, Alessandra; Marongiu, Bruno; Lai, Adolfo

    2004-09-01

    Beta-cyclodextrin (beta-CD) inclusion complexes with carvacrol (1), thymol (2), and eugenol (3) (components of essential oils of vegetable origin) were prepared by the supercritical CO2 technique, and their structural characterization was achieved by means of 1H-NMR in aqueous solution and 13C-CPMAS NMR in the solid state. Evidence of the formation of the inclusion complexes for all the examined systems was obtained by 1H-NMR in solution, while 2D-ROESY-NMR experiments were used to investigate the geometry of inclusion. In addition, the dynamics of these inclusion complexes in the kHz timescale was investigated by analysis of the 1H and 13C spin-lattice relaxation times in the rotating frame.

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

    PubMed

    Louiz, S; Labiadh, H; Abderrahim, R

    2015-01-05

    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, (1)H NMR, (1)H-(1)H NOESY, (13)C 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 × 10(4)M(-1).

  1. 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.

  2. Crystallographic analysis of the thermal motion of the inclusion complex of cyclomaltoheptaose (beta-cyclodextrin) with hexamethylenetetramine.

    PubMed

    Harata, Kazuaki

    2003-02-07

    The crystal structure of the inclusion complex of cyclomaltoheptaose (beta-cyclodextrin) with hexamethylenetetramine was determined at temperatures of 123, 173, 223, and 293 K. The rigid-body motion of the host and guest molecules was evaluated by means of the TLS method that represents the molecular motion in terms of translation, libration, and screw motion. In increasing the temperature from 123 to 293 K, the amplitude of the rigid body vibration of the host molecule was increased from 1.0 to 1.3 degrees in the rotational motion and from 0.16 to 0.17 A in the translational motion. The cyclomaltoheptaose molecule has the flexibility in seven alpha-(1-->4)-linkages, and each glucose unit was in the rotational vibration around an axis through two glycosidic oxygen atoms. As a result, the rigid-body parameters of cyclomaltoheptaose were considered to be overestimated because of including the contribution from the local motion of glucose units. In contrast, for the guest molecule having no structural flexibility, the TLS analysis demonstrated that the atomic thermal vibration was mostly derived from the rigid body motion. The rotational amplitude of hexamethylenetetramine was changed from 5.2 to 6.6 degrees in increasing the temperature from 123 to 293 K, while the change of the translational amplitude was from 0.20 to 0.23 A. The translational motion of the guest molecule was hindered by the inside wall of the host cavity. The molecular motion was characterized by the rotational vibration around the axis through two nitrogen atoms that were involved in the hydrogen-bond formation.

  3. Cyclodextrin Inclusion Polymers Forming Hydrogels

    NASA Astrophysics Data System (ADS)

    Li, Jun

    This chapter reviews the advances in the developments of supramolecular hydrogels based on the polypseudorotaxanes and polyrotaxanes formed by inclusion complexes of cyclodextrins threading onto polymer chains. Both physical and chemical supramolecular hydrogels of many different types are discussed with respect to their preparation, structure, property, and gelation mechanism. A large number of physical supramolecular hydrogels were formed induced by self-assembly of densely packed cyclodextrin rings threaded on polymer or copolymer chains acting as physical crosslinking points. The thermo-reversible and thixotropic properties of these physical supramolecular hydrogels have inspired their applications as injectable drug delivery systems. Chemical supramolecular hydrogels synthesized from polypseudorotaxanes and polyrotaxanes were based on the chemical crosslinking of either the cyclodextrin molecules or the included polymer chains. The chemical supramolecular hydrogels were often made biodegradable through incorporation of hydrolyzable threading polymers, end caps, or crosslinkers, for their potential applications as biomaterials.

  4. Host-guest inclusion system of scutellarein with 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization, and anticancer activity.

    PubMed

    Wang, Fen; Yang, Bo; Zhao, Yulin; Liao, Xiali; Gao, Chuanzhu; Jiang, Ruijian; Han, Bin; Yang, Jian; Liu, Man; Zhou, Rongguang

    2014-01-01

    The inclusion complexation behavior of scutellarein (SCUE) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) has been investigated in both solution and in the solid state. SCUE/HP-β-CD solid system was prepared by suspension method. The formation of SCUE/HP-β-CD complex in aqueous solution was demonstrated by fluorescence spectroscopy, and the Job plot showed a maximum at a molar fraction of 0.5, indicating 1:1 inclusion complexation between SCUE and HP-β-CD. However, SCUE/HP-β-CD inclusion complex was characterized by means of XRD, DSC, (1)H, and two-dimensional NMR. Through the complexation between HP-β-CD and SCUE, the water solubility and antitumor activity of SCUE were obviously increased. This satisfactory water solubility and high antitumor activity of the SCUE/HP-β-CD complex will be potentially useful for its application on human colon cancer chemotherapies.

  5. Theoretical and experimental study of a praziquantel and beta-cyclodextrin inclusion complex using molecular mechanic calculations and H1-nuclear magnetic resonance.

    PubMed

    de Jesus, Marcelo Bispo; de Matos Alves Pinto, Luciana; Fraceto, Leonardo Fernandes; Takahata, Yuji; Lino, Antonio C S; Jaime, Carlos; de Paula, Eneida

    2006-06-16

    Praziquantel (PZQ) is a broadly effective anthelminthic drug available for human and veterinary use, being the drug of choice for the treatment of all forms of schistosomiasis. Nevertheless, large doses are required in order to achieve adequate concentrations at the target site due to the poor solubility of PZQ and its significant first pass metabolism. To improve it, avoiding efficiency loss, we have designed a controlled-release system, in which PZQ was encapsulated in beta-cyclodextrin (beta-CD). The inclusion complexes between PZQ/beta-CD were studied at two different stoichiometries 1:1 and 1:2, through experimental and theoretical analysis. Molecular modeling calculations were used to foresee the better stoichiometry of the complex formed as well as the possible orientations of PZQ inside the beta-CD cavity. The complexes prepared were analyzed through H1 two-dimensional nuclear magnetic resonance (H1 2D-NMR) experiments, which provide (evidences) for the 1:1 complexation of PZQ/beta-CD. H1 2D-NMR also revealed details of PZQ/beta-CD molecular interaction, in which the isoquinoline ring of praziquantel is located inside the beta-CD cavity. Finally, phase-solubility diagrams revealed a five-fold increase in praziquantel water solubility upon addition of increasing beta-CD concentrations up to 16 mM, corresponding to the solubility of beta-CD itself. The solubilization profile is consistent with 1:1 stoichiometry of the PZQ/beta-CD complex while the solubilization effect will certainly increase the pharmacological activity of praziquantel.

  6. Anti-aggregatory effect of cyclodextrins in the refolding process of recombinant growth hormones from Escherichia coli inclusion bodies.

    PubMed

    Bajorunaite, Egle; Cirkovas, Andrejus; Radzevicius, Kostas; Larsen, Kim Lambertsen; Sereikaite, Jolanta; Bumelis, Vladas-Algirdas

    2009-06-01

    Cyclodextrins with different ring size and ring substituents were tested for recombinant mink and porcine growth hormones aggregation suppression in the refolding process from Escherichia coli inclusion bodies. Methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin show a positive effect on the aggregation suppression of both proteins. The influence of different methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin concentrations on the renaturation yield of both growth hormones was investigated. Moreover, methyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin suppress not only folding-related, but also temperature-related aggregates formation of both proteins. Circular dichroism experiments (monitoring of protein solution turbidity by registering high tension voltage) showed that the onset temperature of aggregation of both growth hormones increased with increasing 2-hydroxypropyl-beta-cyclodextrin concentration. In conclusion, cyclodextrins have perspectives in biotechnology of veterinary growth hormones not only for protein production, but also for its storage.

  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. 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.

  9. Effect of dimethyl-beta-cyclodextrin on nitrazepam stability.

    PubMed

    Saleh, S I; Rahman, A A; Aboutaleb, A E; Nakai, Y; Ahmed, M O

    1993-01-01

    Nitrazepam was found to form an inclusion complex with heptakis; 2,6 di-O-methyl-beta-cyclodextrin (DM-beta-CD) in solution. The phase solubility diagram was found to be AL type with no precipitation of the inclusion complex formed. The kinetic studies of nitrazepam hydrolysis in DM-beta-CD solution at 30, 40 and 50 degrees C was followed spectrophotometrically, as the degradation products of the drug did not interfere with such assay. It was found that the degradation of nitrazepam in acidic media followed the first order reaction kinetics at the temperatures studied. Inclusion complexation of nitrazepam in DM-beta-CD resulted in a relatively improved stability of the drug in solution at 30 degrees C. On the other hand, no appreciable stabilization was achieved at higher temperatures (40 and 50 degrees C).

  10. beta-cyclodextrins-based inclusion complexes of CoFe(2)O(4) magnetic nanoparticles as catalyst for the luminol chemiluminescence system and their applications in hydrogen peroxide detection.

    PubMed

    He, Shaohui; Shi, Wenbing; Zhang, Xiaodan; Li, Jian; Huang, Yuming

    2010-06-30

    beta-cyclodextrins (beta-CD)-based inclusion complexes of CoFe(2)O(4) magnetic nanoparticles (MNPs) were prepared and used as catalysts for chemiluminescence (CL) system using the luminol-hydrogen peroxide CL reaction as a model. The as-prepared inclusion complexes were characterized by XRD (X-ray diffraction), TGA (thermal gravimetric analysis) and FT-IR. The oxidation reaction between luminol and hydrogen peroxide in basic media initiated CL. The effect of beta-CD-based inclusion complexes of CoFe(2)O(4) magnetic nanoparticles and naked CoFe(2)O(4) magnetic nanoparticles on the luminol-hydrogen peroxide CL system was investigated. It was found that inclusion complexes between beta-CD and CoFe(2)O(4) magnetic nanoparticles could greatly enhance the CL of the luminol-hydrogen peroxide system. Investigation on the kinetic curves and the chemiluminescence spectra of the luminol-hydrogen peroxide system demonstrates that addition of CoFe(2)O(4) MNPs or inclusion complexes between beta-CD and CoFe(2)O(4) MNPs does not produce a new luminophor of the chemiluminescent reaction. The luminophor for the CL system was still the excited-state 3-aminophthalate anions (3-APA*). The enhanced CL signals were thus ascribed to the possible catalysis from CoFe(2)O(4) MNPs or inclusion complexes between beta-CD and CoFe(2)O(4) nanoparticles. The feasibility of employing the proposed system for hydrogen peroxide sensing was also investigated. Experimental results showed that the CL emission intensity was linear with hydrogen peroxide concentration in the range of 1.0 x 10(-7) to 4.0 x 10(-6) mol L(-1) with a detection limit of 2.0 x 10(-8) mol L(-1) under optimized conditions. The proposed method has been used to determine hydrogen peroxide in water samples successfully.

  11. Encapsulation of olive leaf extract in beta-cyclodextrin.

    PubMed

    Mourtzinos, Ioannis; Salta, Fotini; Yannakopoulou, Konstantina; Chiou, Antonia; Karathanos, Vaios T

    2007-10-03

    Olive leaf extract, rich in oleuropein, formed an inclusion complex with beta-cyclodextrin (beta-CD) upon mixing of the components in aqueous media and subsequent freeze-drying. Inclusion complex formation was confirmed by differential scanning calorimetry (DSC). DSC thermograms indicated that the endothermic peaks of both the olive leaf extract and the physical mixture of olive leaf extract with beta-CD, attributed to the melting of crystals of the extract, were absent in DSC thermogram of inclusion complex. Moreover, DSC studies under oxidative conditions indicated that the complex of olive leaf extract with beta-CD was protected against oxidation, since it remained intact at temperatures where the free olive leaf extract was oxidized. Phase solubility studies afforded A L type diagrams, 1:1 complex stoichiometry, a moderate binding constant ( approximately 300 M (-1)), and an increase of the aqueous solubility by approximately 50%. The formation of the inclusion complex was also confirmed by nuclear magnetic resonance (NMR) studies of beta-CD solutions in the presence of both pure oleuropein and olive leaf extract. The NMR data have established the formation of a 1:1 complex with beta-CD that involves deep insertion of the dihydroxyphenethyl moiety inside the cavity from its secondary side.

  12. Antibacterial electrospun nanofibers from triclosan/cyclodextrin inclusion complexes.

    PubMed

    Celebioglu, Asli; Umu, Ozgun C O; Tekinay, Turgay; Uyar, Tamer

    2014-04-01

    The electrospinning of nanofibers (NF) from cyclodextrin inclusion complexes (CD-IC) with an antibacterial agent (triclosan) was achieved without using any carrier polymeric matrix. Polymer-free triclosan/CD-IC NF were electrospun from highly concentrated (160% CD, w/w) aqueous triclosan/CD-IC suspension by using two types of chemically modified CD; hydroxypropyl-beta-cyclodextrin (HPβCD) and hydroxypropyl-gamma-cyclodextrin (HPγCD). The morphological characterization of the electrospun triclosan/CD-IC NF by SEM elucidated that the triclosan/HPβCD-IC NF and triclosan/HPγCD-IC NF were bead-free having average fiber diameter of 520 ± 250 nm and 1,100 ± 660 nm, respectively. The presence of triclosan and the formation of triclosan/CD-IC within the fiber structure were confirmed by (1)H-NMR, FTIR, XRD, DSC, and TGA studies. The initial 1:1 molar ratio of the triclosan:CD was kept for triclosan/HPβCD-IC NF after the electrospinning and whereas 0.7:1 molar ratio was observed for triclosan/HPγCD-IC NF and some uncomplexed triclosan was detected suggesting that the complexation efficiency of triclosan with HPγCD was lower than that of HPβCD. The antibacterial properties of triclosan/CD-IC NF were tested against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria. It was observed that triclosan/HPβCD-IC NF and triclosan/HPγCD-IC NF showed better antibacterial activity against both bacteria compared to uncomplexed pure triclosan.

  13. β-Cyclodextrin- para-aminosalicylic acid inclusion complexes

    NASA Astrophysics Data System (ADS)

    Roik, N. V.; Belyakova, L. A.; Oranskaya, E. I.

    2010-11-01

    Complex formation of β-cyclodextrin with para-aminosalicylic acid in buffer solutions is studied by UV spectroscopy. It is found that the stoichiometric proportion of the components in the β-cyclodextrin-para-aminosalicylic acid inclusion complex is 1:1. The Ketelar equation is used to calculate the stability constants of the inclusion complexes at different temperatures. The thermodynamic parameters of the complex formation process (ΔG, ΔH, ΔS) are calculated using the van't Hoff equation. The 1:1 β-cyclodextrin-para-aminosalicylic acid inclusion complex is prepared in solid form and its characteristics are determined by IR spectroscopic and x-ray diffraction techniques.

  14. Beta-cyclodextrin-based ferrocene-imprinted gold electrodes.

    PubMed

    Chmurski, Kazimierz; Temeriusz, Andrzej; Bilewicz, Renata

    2003-11-01

    A new stepwise self-assembly procedure is described for the preparation of functional cyclodextrin-modified electrodes. The approach is based on the formation of alkanethiol/lipoylamide-beta-cyclodextrin monolayers with the thiol component responsible for blocking of the electrode surface and lipoylamide-beta-cyclodextrin molecules-for controlled opening of the access of the electroactive probe to the electrode. Functionalization of the electrode is achieved by means of a new cyclodextrin derivative-mono(6-deoxy-6-lipoylamide)-per-2,3,6-O-acetyl-beta-cyclodextrin-prepared in the peracetyl form and deacetylated directly on the electrode surface following the cyclodextrin self-assembly. The progress of deacetylation was monitored by the MALDI MS technique. Deacetylation caused opening of the active sites toward solution probes. The response toward ferrocene was found to be highly improved when ferrocene was added to the solution following self-assembly of cyclodextrin but prior to the thiol self-assembly step (imprinting method). The proposed synthesis and sequential monolayer formation scheme lead to well-organized and stable modified electrode surfaces with improved sensitivity toward solution species compared to other procedures of electrode modification with the cyclodextrin derivatives.

  15. Improvement of antifungal activity of 10-undecyn-1-ol by inclusion complexation with cyclodextrin derivatives.

    PubMed

    Neoh, Tze Loon; Tanimoto, Takahiro; Ikefuji, Shuichi; Yoshii, Hidefumi; Furuta, Takeshi

    2008-05-28

    The inclusion complexation behavior between 10-undecyn-1-ol and cyclodextrin (CD) derivatives, namely, randomly methylated beta-CD (RM-beta-CD) and hydroxypropyl-beta-CD (HP-beta-CD), was studied in terms of solubility improvement, apparent stability constant, and the inclusion ratios of the resultant inclusion complexes. The aqueous solubility of 10-undecyn-1-ol was greatly improved through complexation with the CD derivatives. RM-beta-CD is comparatively more efficient in solubilizing 10-undecyn-1-ol with an apparent stability constant outstripping that of HP-beta-CD by about an order of magnitude. Comparative in vitro evaluations of the growth inhibition effects of inclusion complex solutions toward Rosellinia necatrix, a phytopathogenic fungus, were performed. In comparison with the positive control, appreciable improvements of the antifungal activity of 10-undecyn-1-ol through the addition of CD derivatives were observed visually. The improvement was evaluated in terms of area covered by the mycelia of Rosellinia necatrix and their growth rate. RM-beta-CD was proven to be more effective compared to HP-beta-CD with regard to the reduction of both fungal mycelium-covered area and growth rate constant, presumably owing to greater solubility enhancement by RM-beta-CD and thus the bioavailability of 10-undecyn-1-ol. Inclusion complexation of 10-undecyn-1-ol with CD derivatives suggests a potential means for production of an environmentally friendly 10-undecyn-1-ol-based fungicide to counteract R. necatrix.

  16. Drug carrier systems based on water-soluble cationic beta-cyclodextrin polymers.

    PubMed

    Li, Jianshu; Xiao, Huining; Li, Jiehua; Zhong, YinPing

    2004-07-08

    This study was designed to synthesize, characterize and investigate the drug inclusion property of a series of novel cationic beta-cyclodextrin polymers (CPbetaCDs). Proposed water-soluble polymers were synthesized from beta-cyclodextrin (beta-CD), epichlorohydrin (EP) and choline chloride (CC) through a one-step polymerization procedure by varying molar ratio of EP and CC to beta-CD. Physicochemical properties of the polymers were characterized with colloidal titration, nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC) and aqueous solubility determination. The formation of naproxen/CPbetaCDs inclusion complexes was confirmed by NMR and fourier transform infrared spectroscopy (FT-IR). Cationic beta-CD polymers showed better hemolytic activities than parent beta-CD and neutral beta-CD polymer in hemolysis test. The morphological study of erythrocytes revealed a cell membrane invagination induced by the cationic groups. The effects of molecular weight and charge density of the polymers on their inclusion and release performance of naproxen were also investigated through phase-solubility and dissolution studies. It was found that the cationic beta-CD polymers with high molecular weight or low charge density exhibited better drug inclusion and dissolution abilities.

  17. Selective binding of chiral molecules of cinchona alkaloid by beta- and gamma-cyclodextrins and organoselenium-bridged bis(beta-cyclodextrin)s.

    PubMed

    Liu, Yu; Li, Li; Zhang, Heng-Yi; Fan, Zhi; Guan, Xu-Dong

    2003-02-01

    The inclusion complexation behavior of chiral members of cinchona alkaloid with beta- and gamma-cyclodextrins (1 and 2) and 6,6(')-trimethylenediseleno-bridged bis(beta-cyclodextrin) (3) was assessed by means of fluorescence and 2D-NMR spectroscopy. The spectrofluorometric titrations have been performed in aqueous buffer solution (pH 7.20) at 25.0 degrees C to determine the stability constants of the inclusion complexation of 1-3 with guest molecules (i.e., cinchonine, cinchonidine, quinine, and quinidine) in order to quantitatively investigate the molecular selective binding ability. The stability constants of the resulting complexes of 2 with guest molecules are larger than that of 1. As a result of cooperative binding, the stability constants of inclusion complexation of dimeric beta-cyclodextrin 3 with cinchonidine and cinchonine are higher than that of parent 1 by factor of 4.5 and 2.4, respectively. These results are discussed from the viewpoint of the size-fit and geometric complementary relationship between the host and guest.

  18. 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.

  19. Thermodynamics of inclusion complexes between cyclodextrins and isoniazid

    NASA Astrophysics Data System (ADS)

    Terekhova, I. V.; Kumeev, R. S.

    2010-01-01

    Complex formation of α- and β-cyclodextrins with isoniazid, a antituberculous pharmaceutical, is studied using such methods as calorimetry and 1H NMR at 298.15 K. On the basis of the obtained experimental data, it is shown that α- and β-cyclodextrins form 1 : 1 inclusion complexes with isoniazid, which are characterized by low stability in aqueous solution. Along with this, deeper penetration of isoniazid into the cavity of β-cyclodextrin, accompanied by more intensive dehydration of the reagents, is observed. The results are interpreted in terms of influence of structure of reagents and their state in solution on the binding mode, driving forces, and thermodynamic parameters of the complex formation.

  20. Crystal structure of recombinant soybean beta-amylase complexed with beta-cyclodextrin.

    PubMed

    Adachi, M; Mikami, B; Katsube, T; Utsumi, S

    1998-07-31

    In order to study the interaction of soybean beta-amylase with substrate, we solved the crystal structure of beta-cyclodextrin-enzyme complex and compared it with that of alpha-cyclodextrin-enzyme complex. The enzyme was expressed in Escherichia coli at a high level as a soluble and catalytically active protein. The purified recombinant enzyme had properties nearly identical to those of native soybean beta-amylase and formed the same crystals as the native enzyme. The crystal structure of recombinant enzyme complexed with beta-cyclodextrin was refined at 2. 07-A resolution with a final crystallographic R value of 15.8% (Rfree = 21.1%). The root mean square deviation in the position of C-alpha atoms between this recombinant enzyme and the native enzyme was 0.22 A. These results indicate that the expression system established here is suitable for studying structure-function relationships of beta-amylase. The conformation of the bound beta-cyclodextrin takes an ellipsoid shape in contrast to the circular shape of the bound alpha-cyclodextrin. The cyclodextrins shared mainly two glucose binding sites, 3 and 4. The glucose residue 4 was slightly shifted from the maltose binding site. This suggests that the binding site of the cyclodextrins is important for its holding of a cleaved substrate, which enables the multiple attack mechanism of beta-amylase.

  1. Investigation of transport of genistein, daidzein and their inclusion complexes prepared with different cyclodextrins on Caco-2 cell line.

    PubMed

    Daruházi, Agnes Emma; Kiss, Tímea; Vecsernyés, Miklós; Szente, Lajos; Szőke, Eva; Lemberkovics, Eva

    2013-10-01

    Isoflavonoids are widespread constituents in medical plants especially in legumes (Fabaceae), but occur in other different plant families as well (Rosaceae, Iridaceae, Amaranthaceae). Their antioxidant, estrogen-like, anti-inflammatory and analgesic effects make them promising compounds in therapy of important disorders especially in estrogen related diseases. Poor solubility in aqueous system of genistein and daidzein needs a solubility enhancement for pharmaceutical use. These compounds are suitable guest molecules for inclusion complex formation with cyclodextrins (CDs) considering matching their size and polarity. The molecular encapsulation with beta-cyclodextrin (β-CD), gamma-cyclodextrin (γ-CD), hydroxypropyl-beta-cyclodextrin (HP-β-CD) and random methyl-beta cyclodextrin (RAMEB-CD) results in a solid, molecularly dispersed form and in a significantly improved aqueous solubility of genistein and daidzein. Determining enhancement in solubility and bioavailability we investigated the transport of these inclusion complexes across Caco-2 cell line comparing that of the pure compounds and found significant improving effect of the different CD derivatives on membrane permeation of the two isoflavone aglycons.

  2. Nanoassemblies driven by cyclodextrin-based inclusion complexation.

    PubMed

    Kang, Yang; Guo, Kun; Li, Bang-Jing; Zhang, Sheng

    2014-10-04

    Nanoscaled supramolecular systems have attracted significant attention because of their promising applications in many fields. This review focuses on recent advances in the construction of nanoassemblies driven by cyclodextrin (CD)-based inclusion complexation and their application in biomedical and biomimetic fields. As a result of the reversibility of the CD-based host-guest interactions, CD-based driving forces provide the opportunity to generate complex and sophisticated nanoassemblies with tunable properties.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

    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 α, β or γ). 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 βCD 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.

  5. Complexation with tolbutamide modifies the physicochemical and tableting properties of hydroxypropyl-beta-cyclodextrin.

    PubMed

    Suihko, E; Korhonen, O; Järvinen, T; Ketolainen, J; Jarho, P; Laine, E; Paronen, P

    2001-03-14

    The physicochemical and tableting properties of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and its tolbutamide (TBM) complex were studied. The kinetics of TBM/HP-beta-CD inclusion complex formation in solution were determined by the phase solubility method. Solid complexes were prepared by freeze-drying and spray-drying. Water sorption-desorption behaviour of the materials were studied and compacts were made using a compaction simulator. TBM and HP-beta-CD formed 1:1 inclusion complexes in aqueous solution with an apparent stability constant of 63 M(-1). HP-beta-CDs and TBM/HP-beta-CD complexes were amorphous whereas the freeze-dried and spray-dried TBMs were polymorphic forms II and I, respectively. Sorption-desorption studies showed that HP-beta-CDs were deliquescent at high relative humidities. TBM/HP-beta-CD complexes had slightly lower water contents at low relative humidities than the physical mixtures. However, at high humidities their water sorption and desorption behaviours were similar to those of corresponding physical mixtures, indicating a glass transition of the complexed materials. TBM/HP-beta-CD complexes demonstrated a worse compactability than similarly prepared HP-beta-CDs or physical mixtures. Also particle properties that resulted from these preparation methods affected the compactability of the materials. In conclusion, the physicochemical and tableting properties of HP-beta-CD were modified by complexation it with TBM.

  6. 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.

    PubMed

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

    2014-07-15

    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.

  7. Study on the supramolecular multirecognition mechanism of beta-naphthol/beta-cyclodextrin/anionic surfactant in a tolnaftate hydrolysis system.

    PubMed

    Bo, Tang; Xu, Wang; Jing, Wang; Chengguang, Yu; Zhenzhen, Chen; Yi, Ding

    2006-05-04

    Based on the fact that tolnaftate degrade to beta-naphthol sodium (RONa) at 5.00 mol/L NaOH solution and RO(-) was protonated to ROH after being acidified and adjusted to the pH 4.50 by acetic acid-sodium acetate buffer solution, we studied and discussed the mechanism of the supramolecular multirecognition interaction among the anionic surfactants sodium lauryl sulfate (SLS), beta-cyclodextrin (beta-CD), and beta-naphthol (ROH) by means of fluorescence spectrum, surface tension of the solution, infrared spectrograms, and (1)HNMR spectroscopy. The apparent formation constant of the ternary inclusion complex was determined to be (5.48 +/- 0.13) x 10(3) L(2)/mol(2). The thermodynamic parameters (DeltaG degrees, DeltaH degrees, DeltaS degrees ) for the formation of the inclusion complexes were obtained from the van't Hoff equation. It was indicated that the multiple and synergistic protection effect of SLS and beta-CD on the excited singlet state ROH played very important roles in the enhancement of the fluorescence of ROH. Results showed that, at room temperature, the naphthalene ring of ROH and the hydrophobic hydrocarbon chain of SLS were included into the cavity of beta-CD to form a ROH/SLS/beta-CD ternary inclusion complex with stoichiometry of 1:1:1, which provided effective protection for the excited state of ROH and increased the fluorescent intensity of ROH obviously.

  8. Environmental significance of the diclofop-methyl and cyclodextrin inclusion complexes.

    PubMed

    Cai, Xiyun; Zhang, Anping; Liu, Weiping

    2006-01-01

    Cyclodextrins (CDs) possess a hydrophilic external surface and a hydrophobic cavity. They are thus highly soluble and, in the meantime, effectively form inclusion complexes with hydrophobic organic compounds to enhance their solubilities. In this study, the complexation between modified beta-CDs and the herbicide diclofop-methyl (DM), (2-(4-(2,4-dichlorophenoxy)-phenoxy) propionate), was investigated. The complexation was confirmed by the shifts in the wavelengths of maximum ultra violet (UV) absorption and fluorescence excitation/emission. The deuterium isotope effects indicate that in the presence of beta-CDs the solubility of DM was lower while that of diclofop was higher in D2O than in H2O, suggesting the primary role of hydrophobic interactions in complexation. The solubility of DM was enhanced in the presence of beta-CDs, the extent of which depended on the modification of beta-CDs. The complexation reduced the hydrolysis of DM and hence increased its stability. The small inconsistency in the power of beta-CDs between hydrolysis retardation and solubilization suggests that hydrolysis was affected by the properties of beta-CDs and the configuration of DM in the complexes. Use of beta-CDs may thus result in the mobilization of soil DM. Properly modified beta-CDs may be utilized as formulation additives for improved delivery of DM and for enhanced environmental remediation.

  9. 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

  10. The use of beta-cyclodextrin in the manufacturing of disintegrating pellets with improved dissolution performances.

    PubMed

    Zema, Lucia; Palugan, Luca; Maroni, Alessandra; Foppoli, Anastasia; Sangalli, Maria Edvige; Gazzaniga, Andrea

    2008-01-01

    It has recently been highlighted that the release behavior of pellets containing microcystalline cellulose (MCC) as the spheronizing agent may be impaired by the lack of disintegration. Although alternative spheronizing excipients have been proposed, their overall advantages have not thoroughly been assessed. In the present work, the possible use of beta-cyclodextrin (betaCD) was therefore explored for the manufacturing of pellets with a potential for effective disintegration and immediate release of poorly soluble active ingredients. MCC/betaCD powder formulations containing no drug or model drugs with different water solubility, able to form inclusion compounds with the employed cyclodextrin, were pelletized by agglomeration in rotary fluid bed equipment. By applying successive statistical experimental designs, the most critical formulation and operating parameters were identified and optimal manufacturing processes were ultimately set up. High yields of pellets provided with satisfactory physical-technological characteristics were obtained using powder formulations with up to 80% betaCD. Based on dissolution testing results, the suitability of betaCD for the preparation of disintegrating MCC-containing pellets with improved dissolution performance was finally demonstrated.

  11. Inclusion and functionalization of polymers with cyclodextrins: current applications and future prospects.

    PubMed

    Folch-Cano, Christian; Yazdani-Pedram, Mehrdad; Olea-Azar, Claudio

    2014-09-09

    The numerous hydroxyl groups available in cyclodextrins are active sites that can form different types of linkages. They can be crosslinked with one another, or they can be derivatized to produce monomers that can form linear or branched networks. Moreover, they can form inclusion complexes with polymers and different substrates, modifying their physicochemical properties. This review shows the different applications using polymers with cyclodextrins, either by forming inclusion complexes, ternary complexes, networks, or molecularly imprinted polymers (MIPs). On one hand, the use of cyclodextrins enhances the properties of each polymer, and on the other the use of polymers decreases the amount of cyclodextrins required in different formulations. Both cyclodextrins and polymers contribute synergistically in several applications such as pharmacological, nutritional, environmental, and other industrial fields. The use of polymers based on cyclodextrins is a low cost easy to use potential tool with great future prospects.

  12. Enhancement of bioavailability of cinnarizine from its beta-cyclodextrin complex on oral administration with DL-phenylalanine as a competing agent.

    PubMed

    Tokumura, T; Nanba, M; Tsushima, Y; Tatsuishi, K; Kayano, M; Machida, Y; Nagai, T

    1986-04-01

    The present investigation is concerned with an improvement of the bioavailability of cinnarizine by administering its beta-cyclodextrin complex together with another compound which competes with the beta-cyclodextrin molecule in complex formation in aqueous solution (competing agent). The bioavailability of cinnarizine on oral administration of the cinnarizine-beta-cyclodextrin inclusion complex was enhanced by the simultaneous administration of DL-phenylalanine as a competing agent, e.g., the AUC was 1.9 and 2.7 times as large as those of the cinnarizine-beta-cyclodextrin complex alone and cinnarizine alone, respectively. The enhancement of AUC and Cmax completely depended on the dose of DL-phenylalanine. It was found from these results that DL-phenylalanine acted as a competing agent in the GI tract and the minimum effective dose required of DL-phenylalanine might be 1 g for 50 mg of cinnarizine in the cinnarizine-beta-cyclodextrin complex. Evaluating the competing effect of DL-phenylalanine in vitro using an absorption simulator, it was found that the decreased penetration rate of cinnarizine through the artificial lipid barrier with addition of beta-cyclodextrin was restored with the addition of DL-phenylalanine.

  13. Study on the inclusion complexes of cyclodextrin and sulphonated azo dyes by electrospray ionization mass spectrometry

    NASA Astrophysics Data System (ADS)

    Zhang, Huarong; Chen, Gang; Wang, Ling; Ding, Lan; Tian, Yuan; Jin, Weiqun; Zhang, Hanqi

    2006-05-01

    The inclusion complexes of [alpha]-, [beta]-cyclodextrin ([alpha]-, [beta]-CD) and sulphonated azo dyes ligands (Orange II, Ponceau SX, Allura red AC and Tartrazine) were studied by electrospray ionization mass spectrometry (ESI-MS) and the dissociation constants (KD) of the inclusion complexes were determined. A new method to obtain the dissociation constants of CD-ligand inclusion complexes without curve fitting was developed. Once the total concentrations of CD and ligand have been known, KD can be calculated from the sum peak intensities of free CD and inclusion complex and the number of binding site can be obtained from the mass spectrum. Ponceau SX, Allura red AC and Tartrazine binding to [alpha]-CD form 1:1 inclusion complexes with KD values of 1.33 × 10-5 mol L-1, 4.85 × 10-6 mol L-1 and 7.47 × 10-5 mol L-1, respectively. The obtained KD values of the inclusion complexes of above-mentioned three sulphonated azo dyes ligands binding to [beta]-CD in turn are 3.93 × 10-6 mol L-1, 6.50 × 10-6 mol L-1 and 1.12 × 10-4 mol L-1, respectively. The 1:1 and 1:2 inclusion complexes are found in the systems of CD and Orange II. KD,1 and KD,2 of [alpha]-CD and Orange II inclusion complexes are 4.05 × 10-4 mol L-1 and 4.60 × 10-7 (mol L-1)2, respectively. 3.94 × 10-5 mol L-1 and 1.72 × 10-7 (mol L-1)2 are the KD,1 and KD,2 of [beta]-CD and Orange II inclusion complexes, respectively. The competition experiments were performed to validate the results obtained by one ligand. According to the proposed method, the KD values of inclusion complexes regardless of any stoichiometric relation of host and guest can be obtained.

  14. Reduced migration from flexible poly(vinyl chloride) of a plasticizer containing beta-cyclodextrin derivative.

    PubMed

    Yu, Ong Yong; Chung, Jae Woo; Kwak, Seung-Yeop

    2008-10-01

    The migration of endocrine-disrupting di-(2-ethylhexyl) phthalate (DEHP) poses a serious threat to public health and the environment. In this study, we successfully prepared a plasticizerwith reduced DEHP migration by directly incorporating 2,3,6-per-O-benzoyl-beta-cyclodextrin (Bz-beta-CD) into DEHP. Bz-beta-CD was prepared by esterification between the hydroxyl groups of beta-CD and benzoyl chloride. The presence of this cyclodextrin is expected to facilitate formation of stable complexes through pi-pi association with DEHP molecules. The flexible PVC was prepared with a gelation-fusion process that uses the prepared migration-resistant plasticizer, and its properties (flexibility, thermal stability, and clarity) were evaluated by carrying out DSC and tensile testing, TGA, and haze testing, respectively. No significant changes in the physical properties of the flexible PVC were observed when Bz-beta-CD was added. DEHP migration tests were carried out for the flexible PVC according to the ISO 3826:1993(E) test method, and the quantity of migrated DEHP was then determined with UV-vis spectroscopy. It was found that the addition of Bz-beta-CD decreases the levels of DEHP migration from the flexible PVC samples by almost 40%. We investigated the molecular interaction between Bz-beta-CD and DEHP using molecular mechanics simulations, and we conclude that this reduction in DEHP migration is due to the formation of stabilized pi-pi attractive association and inclusion complexes of Bz-beta-CD and DEHP in flexible PVC.

  15. 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.

  16. Formation and antimicrobial activity of complexes of beta-cyclodextrin and some antimycotic imidazole derivatives.

    PubMed

    Van Doorne, H; Bosch, E H; Lerk, C F

    1988-04-22

    Complex formation between beta-cyclodextrin and six antimycotic imidazole derivatives has been studied. The solubility of all drugs was increased in the presence of beta-cyclodextrin. The smallest increase (approx. 5-fold) was observed for miconazol, and the largest increase (approx. 160-fold) was observed for bifonazol. Apparent 1:1-complex constants were measured and found to decrease in the order: bifonazol greater than ketoconazol greater than tioconazol greater than miconazol greater than itraconazol greater than clotrimazol. The complexes appeared to possess a low, if any, antimicrobial activity. Measurement of inhibition zone sizes, with four test organisms was used to study the release of the antimycotic drugs from topical preparations. The antimycotic drugs were more readily released from topical preparations containing beta-cyclodextrin than from the same vehicles without beta-cyclodextrin. The rationale of beta-cyclodextrin addition to antimycotic topical preparations is discussed.

  17. Preparation, characterization and in vitro dissolution study of Nitrazepam: Cyclodextrin inclusion complex.

    PubMed

    Patel, J S; Patel, R P

    2012-03-01

    The objectives of this research were to prepare and characterize inclusion complexes of Nitrazepam with Hydroxypropyl-β-cyclodextrin (HPβCD) and Sulfobutyl ether β-cyclodextrin (SBEβCD) to study the effect of complexation on the dissolution rate of Nitrazepam, a water-insoluble drug. The phase solubility profile of Nitrazepam with Hydroxypropyl- β-cyclodextrin and Sulfobutyl ether β-cyclodextrin was an AP-type, indicating the formation of 2:1 stoichiometric inclusion complexes. Gibbs free energy values were all negative, indicating the spontaneous nature Nitrazepam solubilization and their value decreased with increase in the cyclodextrin concentration, demonstrating that the reaction conditions became more favorable as the concentration of cyclodextrins increased. Complexes of Nitrazepam were prepared with cyclodextrin using various methods such as physical mixing, kneading, spray-drying and lyophilization. The complexes were characterized by Differential scanning calorimetry, Fourier-transform infrared, scanning electron microscopy and powder X-ray diffraction studies. These studies indicated that a complex prepared by lyophilization had successful inclusion of the Nitrazepam molecule into the cyclodextrin cavity. Complexation resulted in a marked improvement in the solubility and wettability of Nitrazepam. Among all the samples, a complex prepared with Sulfobutyl ether β-cyclodextrin by lyophilization had the greatest improvement in the in vitro rate of Nitrazepam dissolution. The mean dissolution time for Nitrazepam decreased significantly after preparing complexes. The similarity factor indicated a significant difference between the release profiles of Nitrazepam from complexes, physical mixtures and plain Nitrazepam. To conclude that, the tablets containing complexes prepared with Cyclodextrins had significant improvement in the release profile of Nitrazepam as compared to tablets containing Nitrazepam without cyclodextrin.

  18. 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

    2004-07-08

    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.

  19. Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-β-cyclodextrin.

    PubMed

    Nair, Anroop B; Attimarad, Mahesh; Al-Dhubiab, Bandar E; Wadhwa, Jyoti; Harsha, Sree; Ahmed, Mueen

    2014-11-01

    The therapeutic potential of acyclovir is limited by the low oral bioavailability owing to its limited aqueous solubility and low permeability. The present study was a systematic investigation on the development and evaluation of inclusion complex using hydroxypropyl-β-cyclodextrin for the enhancement of oral bioavailability of acyclovir. The inclusion complex of acyclovir was prepared by kneading method using drug: hydroxypropyl-β-cyclodextrin (1:1 mole). The prepared inclusion complex was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, NMR spectroscopy and evaluated in vitro by dissolution studies. In vivo bioavailability of acyclovir was compared for inclusion complex and physical mixture in rat model. Phase solubility studies indicate the formation of acyclovir-hydroxypropyl-β-cyclodextrin complex with higher stability constant and linear enhancement in drug solubility with increase in hydroxypropyl-β-cyclodextrin concentration. Characterization of the prepared formulation confirms the formation of acyclovir-hydroxypropyl-β-cyclodextrin inclusion complex. Dissolution profile of inclusion complex demonstrated rapid and complete release of acyclovir in 30 min with greater dissolution efficiency (90.05 ± 2.94%). In vivo pharmacokinetic data signify increased rate and extent of acyclovir absorption (relative bioavailability ∼160%; p < 0.0001) from inclusion complex, compared to physical mixture. Given the promising results in the in vivo studies, it can be concluded that the inclusion complex of acyclovir could be an effective and promising approach for successful oral therapy of acyclovir in the treatment of herpes viruses.

  20. Solubility enhancement of steviol glycosides and characterization of their inclusion complexes with gamma-cyclodextrin.

    PubMed

    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 (13)C 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.

  1. 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

  2. Inclusion complexes of trivalent lutetium cations with an acidic derivative of per(3,6-anhydro)-alpha-cyclodextrin.

    PubMed

    Bonnet, Célia; Gadelle, Andrée; Pécaut, Jacques; Fries, Pascal H; Delangle, Pascale

    2005-02-07

    The cyclodextrin derivative (hexakis (2-O-carboxymethyl-3,6-anhydro)-alpha-cyclodextrin) forms mono- and bimetallic complexes with lutetium(III) in aqueous solution; the X-ray structure of the binuclear complex [Lu2(ACX)(H2O)2] is the first example of a lanthanide-cyclodextrin inclusion complex.

  3. Structure and stability of oligomer/α-cyclodextrin inclusion complexes.

    NASA Astrophysics Data System (ADS)

    Hunt, Marcus; Villar, Silvia; Gomez, Marian; Tonelli, Alan; Balik, Maury

    2007-03-01

    Cyclomaltohexaose (α-cyclodextrin, α-CD) can form inclusion complexes (ICs) with polymer molecules in the columnar crystal in which α-CD molecules stack to form a molecular tube. Complementary water vapor sorption and wide-angle X-ray diffractomery (WAXD) were performed on oligomer/α-CD ICs to probe their structures and stabilities. To discern the effect of guest molecule hydrophobicity on water adsorption isotherms, polyethylene glycol (PEG, MW = 600 g/mol) and hexatriacontane (HTC) guests were used. Sorption isotherms for PEG/α-CD IC are similar to those obtained for pure α-CD and PEG, suggesting the presence of dethreaded PEG in the sample. WAXD collected before and after water vapor sorption of PEG/α-CD IC indicated a partial conversion from columnar to cage crystal structure, the thermodynamically preferred structure for pure α-CD, due to dethreading of PEG. This behavior does not occur for HTC/α-CD IC. Sorption isotherms collected at 20, 30, 40 and 50 C allowed the calculation of differential heats of adsorption and integral entropies of adsorbed water, while solid-state ^13C NMR suggested a dramatic increase in HTC and α-CD mobilities upon complexation.

  4. 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.

  5. Complexation study of brilliant cresyl blue with beta-cyclodextrin and its derivatives by UV-vis and fluorospectrometry.

    PubMed

    Zhang, Qing-Feng; Jiang, Zi-Tao; Guo, Yu-Xian; Li, Rong

    2008-01-01

    The complexation reactions of brilliant cresyl blue (BCB) with beta-cyclodextrin (beta-CD), mono[2-O-(2-hydroxypropyl)]-beta-CD (2-HP-beta-CD), mono[2-O-(2-hydroxyethyl)]-beta-CD (2-HE-beta-CD), and heptakis(2,6-di-methyl) -beta-CD (DM-beta-CD) were investigated using UV-vis and fluorospectrometry. The complexation between BCB and CDs could inhibit the aggregation of BCB molecules and could cause its absorbance at 634nm gradually increasing. The fluorescence of BCB was also enhanced with the addition of CDs. The fluorescence enhancement was more notable in neutral and acidic media than in basic media. Hildebrand-Benesi equation was used to calculate the formation constants of beta-CDs with BCB based on the fluorescence differences in the CDs solution. The stoichiometry ratio was found to be 1:1. The complexing capacities of beta-CD and its three derivatives were compared and the results followed the order: 2-HP-beta-CD>2-HE-beta-CD>DM-beta-CD>beta-CD. The effect of temperature on the formation of BCB-beta-CD inclusion complexes has also been examined. The results revealed that the formation constants decreased with the increase of temperature from 1038.9 to 491.6l/mol. Enthalpy and entropy values were calculated and the values were -25.77kJ/mol and 35.04J/kmol, respectively. The thermodynamic measurements suggest that the inclusive process was enthalpic favor. The release of high-energy water molecules and Van der Waals force played an important role in the inclusive process.

  6. Inclusion complex of benzocaine and β-cyclodextrin: 1H NMR and isothermal titration calorimetry studies

    NASA Astrophysics Data System (ADS)

    Mic, Mihaela; Pırnǎu, Adrian; Bogdan, Mircea; Turcu, Ioan

    2013-11-01

    The supramolecular structure of the inclusion complex of β-cyclodextrin with benzocaine in aqueous solution has been investigated by 1H NMR spectroscopy and isothermal titration nanocalorimetry (ITC). Analysis of 1H NMR data by continuous variation method indicates that the benzocaine: β-cyclodextrin inclusion complex occurs and has a 1:1 stoichiometry. Rotating frame NOE spectroscopy (ROESY) was used to ascertain the solution geometry of the host-guest complex which indicates that the benzocaine molecule was included with the aromatic ring into the cyclodextrin cavity. Although the affinity of benzocaine for cyclodextrin is relatively high, the association constant cannot be measured using ITC due to the low solubility of benzocaine in water.

  7. Removal of cholesterol from Cheddar cheese by beta-cyclodextrin.

    PubMed

    Kwak, H S; Jung, C S; Shim, S Y; Ahn, J

    2002-12-04

    This study was carried out to determine the cholesterol removal rate and resulting changes in flavor, fatty acid and bitter amino acid production in reduced-cholesterol Cheddar cheese, made by cream separation followed by 10% beta-cyclodextrin (beta-CD) treatment. The cholesterol removal from the cheese was 92.1%. The production of short-chain free fatty acids (FFAs) increased the ripening time in control and cream-treated cheeses. The quantity of short-chain FFAs released between treatments during ripening was different, while not much difference was found in the production of neutral volatile compounds in the samples. Reduced-cholesterol cheese produced much higher levels of bitter amino acids than the control. In sensory analysis, the texture score of control Cheddar cheese increased significantly with ripening time; however, that of the cream treatment group decreased dramatically with ripening time. On the basis of our results, we conclude that the cheese made from beta-CD-treated cream had a higher rate of cholesterol removal and ripened rapidly.

  8. Pharmacokinetics of 16-dehydropregnenolone hydroxypropyl-β-cyclodextrin inclusion complex following peroral administration.

    PubMed

    Sun, Yangyang; Jia, Lili; Zhou, Hui; Mao, Mengqian; Wang, Xiaobo; Wei, Lan; Sun, Lixin

    2017-03-01

    16-Dehydropregnenolone (16-DHP) is an active compound with an unsatisfied in vivo behavior and poor water-solubility, which limits its clinical application. To improve its in vivo behavior and water-solubility, a Hydroxypropyl-beta-Cyclodextrin (HP-β-CD) inclusion complex of 16-DHP was prepared in this paper. Pharmacokinetic studies after oral administration of 16-DHP-HP-β-CD at doses of 37.5, 75, 150 mg/kg were carried out to investigate its dose proportionality in rats. The relative bioavailability was researched by comparing the area under the plasma concentration-time curve of 16-DHP-HP-β-CD and free 16-DHP after oral administration in rats at the dose of 75 mg/kg. At the same time, tissue distribution of 16-DHP-HP-β-CD after oral administration at the dose of 240 mg/kg in mice was also investigated. Consequently, 16-DHP-HP-β-CD appeared to be a linear pharmacokinetic character after peroral administration to the rat at the doses tested. Compared to free 16-DHP, inclusion complex could significantly improve the relative bioavailability (467%). Tissue distribution studies indicated that 16-DHP-HP-β-CD tended to distribute into stomach, intestine, lung, brain and liver.

  9. Influence of hydroxypropyl-beta-cyclodextrin on transdermal penetration and photostability of avobenzone.

    PubMed

    Yang, Jing; Wiley, Cody J; Godwin, Donald A; Felton, Linda A

    2008-06-01

    The objective of the present study was to determine the effects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the transdermal penetration and photostability of a model ultraviolet A (UVA) absorber, butyl methoxydibenzoylmethane (avobenzone), and to determine the influence of complexation on in vivo photoprotection. Avobenzone-HPCD complexation was demonstrated by differential scanning calorimetry. Formulations containing 0.12 mg/ml avobenzone and up to 30% (w/w) HPCD were prepared. Transdermal penetration was conducted using a modified Franz diffusion cell apparatus. As the concentration of HPCD was increased from 0% to 20%, transdermal permeation increased. Maximum flux occurred at 20% HPCD, where sufficient cyclodextrin was present to completely solubilize all avobenzone. When the concentration of HPCD was increased to 30%, transdermal penetration decreased, suggesting the formation of an avobenzone reservoir on the skin surface. Photostability of avobenzone was investigated under 100, 250, and 500 kJ/m2 UVA irradiation. The 30% HPCD formulation was the most photostable, followed by 20%, 10%, and 0% formulations. In vivo, the 30% HPCD formulation afforded the best photoprotection, as evidenced by the lowest extent of sunburn cell formation and edema induction. This work indicates that inclusion of HPCD in sunscreen formulations may enhance photoprotection by reducing both skin penetration and photodecomposition of UV absorbers.

  10. 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.

  11. Effect of pH and water-soluble polymers on the aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin derivatives.

    PubMed

    Alexanian, Christina; Papademou, Helen; Vertzoni, Maria; Archontaki, Helen; Valsami, Georgia

    2008-11-01

    The aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin (beta-CD) and its alkyl derivatives hydroxypropyl-beta-CD and methyl-beta-CD was studied. We also investigated the effect of water-soluble polymers, hydroxypropylmethyl-cellulose, sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25 degrees C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. beta-CDs increased the aqueous solubility of nimesulide in the following order: methyl-beta-CD > beta-CD > hydroxypropyl-beta-CD. Addition of hydroxypropylmethyl-cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three beta-CDs with nimesulide, while preheating of the polymer at 70 degrees C under sonication resulted in an additional two-fold increase in the aqueous solubility of the drug. Sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus beta-CD, hydroxypropyl-beta-CD and methyl-beta-CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl-cellulose in order to enhance its oral bioavailability.

  12. beta-cyclodextrin derivatives, SBE4-beta-CD and HP-beta-CD, increase the oral bioavailability of cinnarizine in beagle dogs.

    PubMed

    Järvinen, T; Järvinen, K; Schwarting, N; Stella, V J

    1995-03-01

    The absolute bioavailabilities (Fabs) of cinnarizine after oral administration as two modified beta-cyclodextrin (SBE4-beta-CD or HP-beta-CD) solutions, an aqueous suspension, and two capsules in fasted beagle dogs were determined. Cinnarizine was administered orally (25.0 mg) and intravenously (12.5 mg) to four dogs. Blood samples were drawn for 24.5 h postdosing, and cinnarizine levels in plasma were determined by HPLC with spectrofluorometric detection. Cinnarizine pharmacokinetics after iv administration as a 1.25 mg/mL SBE4-beta-CD solution followed triexponential behavior (t1/2 = 12.6 +/- 0.4 h and CI = 1.4 +/- 0.17 L/h/kg). A very low bioavailability of cinnarizine with a wide interanimal variation was observed after oral administration as a suspension (Fabs = 8 +/- 4%) or capsule containing only cinnarizine (Fabs = 0.8 +/- 0.4%). Administration of cinnarizine as a CD complex either as a solution (Fabs = 55-60%) or in a capsule (Fabs = 38 +/- 12%) significantly enhanced the bioavailability. Since the solutions showed excellent bioavailability, the logical conclusion is that, once presented as a solution, cinnarizine is well absorbed and that cinnarizine rapidly dissociates from its inclusion complexes. Presumably, the elevated bioavailability from the SBE4-beta-CD containing capsule was due to rapid dissolution and release of cinnarizine.

  13. Effect of low-molecular-weight beta-cyclodextrin polymer on release of drugs from mucoadhesive buccal film dosage forms.

    PubMed

    Arakawa, Yotaro; Kawakami, Shigeru; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2005-09-01

    We investigated the effect of low-molecular-weight beta-cyclodextrin (beta-CyD) polymer on in vitro release of two drugs with different lipophilicities (i.e., lidocaine and ketoprofen) from mucoadhesive buccal film dosage forms. When beta-CyD polymer was added to hydroxypropylcellulose (HPC) or polyvinylalcohol (PVA) film dosage forms, the release of lidocaine into artificial saliva (pH 5.7) was reduced by 40% of the control. In contrast, the release of ketoprofen from the polymer film was enhanced by addition of beta-CyD polymer to the vehicle. When lidocaine and ketoprofen was incubated with beta-CyD polymer in the artificial saliva, concentration of free lidocaine molecules decreased in a beta-CyD polymer concentration-dependent manner. The association constant with beta-CyD polymer was 6.9+/-0.6 and 520+/-90 M(-1) for lidocaine and ketoprofen, respectively. Retarded release of the hydrophilic lidocaine by beta-CyD polymer might be due to the decrease in thermodynamic activity by inclusion complex formation, whereas enhanced release of the lipophilic ketoprofen by the beta-CyD polymer might be due to prevention of recrystallization occurring after contacting the film with aqueous solution. Thus, effects of low-molecular-weight beta-CyD polymer to the drug release rate from film dosage forms would vary according to the strength of interaction with and the solubility of active ingredient.

  14. 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.

  15. 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.

  16. 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.

  17. Hot-melt extrusion as a continuous manufacturing process to form ternary cyclodextrin inclusion complexes.

    PubMed

    Thiry, Justine; Krier, Fabrice; Ratwatte, Shenelka; Thomassin, Jean-Michel; Jerome, Christine; Evrard, Brigitte

    2017-01-01

    The aim of this study was to evaluate hot-melt extrusion (HME) as a continuous process to form cyclodextrin (CD) inclusion complexes in order to increase the solubility and dissolution rate of itraconazole (ITZ), a class II model drug molecule of the Biopharmaceutics Classification System. Different CD derivatives were tested in a 1:1 (CD:ITZ) molar ratio to obtain CD ternary inclusion complexes in the presence of a polymer, namely Soluplus(®) (SOL). The CD used in this series of experiments were β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD) with degrees of substitution of 0.63 and 0.87, randomly methylated β-cyclodextrin (Rameb(®)), sulfobutylether-β-cyclodextrin (Captisol(®)) and methyl-β-cyclodextrin (Crysmeb(®)). Rheology testing and mini extrusion using a conical twin screw mini extruder were performed to test the processability of the different CD mixtures since CD are not thermoplastic. This allowed Captisol(®) and Crysmeb(®) to be discarded from the study due to their high impact on the viscosity of the SOL/ITZ mixture. The remaining CD were processed by HME in an 18mm twin screw extruder. Saturation concentration measurements confirmed the enhancement of solubility of ITZ for the four CD formulations. Biphasic dissolution tests indicated that all four formulations had faster release profiles compared to the SOL/ITZ solid dispersion. Formulations of HPβCD 0.63 and Rameb(®) even reached 95% of ITZ released in both phases after 1h. The formulations were characterized using thermal differential scanning calorimetry and attenuated total reflectance infra-red analysis. These analyses confirmed that the increased release profile was due to the formation of ternary inclusion complexes.

  18. 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.

  19. 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

  20. Chlorhexidine: beta-cyclodextrin inhibits yeast growth by extraction of ergosterol

    PubMed Central

    Teixeira, K. I. R.; Araújo, P. V.; Sinisterra, R. D.; Cortés, M. E.

    2012-01-01

    Chlorhexidine (Cx) augmented with beta-cyclodextrin (β-cd) inclusion compounds, termed Cx:β-cd complexes, have been developed for use as antiseptic agents. The aim of this study was to examine the interactions of Cx:β-cd complexes, prepared at different molecular ratios, with sterol and yeast membranes. The Minimal Inhibitory Concentration (MIC) against the yeast Candida albicans (C.a.) was determined for each complex; the MICs were found to range from 0.5 to 2 μg/mL. To confirm the MIC data, quantitative analysis of viable cells was performed using trypan blue staining. Mechanistic characterization of the interactions that the Cx:β-cd complexes have with the yeast membrane and assessment of membrane morphology following exposure to Cx:β-cd complexes were performed using Sterol Quantification Method analysis (SQM) and scanning electron microscopy (SEM). SQM revealed that sterol extraction increased with increasing β-cd concentrations (1.71 ×103; 1.4 ×103; 3.45 ×103, and 3.74 ×103 CFU for 1:1, 1:2, 1:3, and 1:4, respectively), likely as a consequence of membrane ergosterol solubilization. SEM images demonstrated that cell membrane damage is a visible and significant mechanism that contributes to the antimicrobial effects of Cx:β-cd complexes. Cell disorganization increased significantly as the proportion of β-cyclodextrin present in the complex increased. Morphology of cells exposed to complexes with 1:3 and 1:4 molar ratios of Cx:β-cd were observed to have large aggregates mixed with yeast remains, representing more membrane disruption than that observed in cells treated with Cx alone. In conclusion, nanoaggregates of Cx:β-cd complexes block yeast growth via ergosterol extraction, permeabilizing the membrane by creating cluster-like structures within the cell membrane, possibly due to high amounts of hydrogen bonding. PMID:24031894

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

    PubMed

    Caira, Mino R; Bourne, Susan A; Samsodien, Halima; Smith, Vincent J

    2015-01-01

    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).

  2. Beta-cyclodextrin conjugates with glucose moieties designed as drug carriers: their syntheses, evaluations using concanavalin A and doxorubicin, and structural analyses by NMR spectroscopy.

    PubMed

    Oda, Yoshiki; Kobayashi, Natsumi; Yamanoi, Takashi; Katsuraya, Kaname; Takahashi, Keiko; Hattori, Kenjiro

    2008-05-01

    Three kinds of beta-cyclodextrin derivatives conjugated with glucose moieties, which were expected as models for a drug carrier targeting the drug delivery systems, were designed and synthesized from beta-cyclodextrin and the natural product, 4-hydroxyphenyl-beta-D-glucopyranoside called arbutin. Arbutin was used because it had a phenyl group with a hydroxyl function which could be used to link the glucose moiety to beta-cyclodextrin. The evaluations of these conjugates as the drug-carrying molecules were done by investigating the molecular interactions with the carbohydrate-binding Concanavalin A (Con A) lectin and the anticancer agent, doxorubicin (DXR), using an SPR optical biosensor. The association constants of the conjugates with immobilized Con A were 2.0 x 10(3) approximately 8.8 x 10(3) M(-1). The result showed that the Con A bound to the glucose moieties from arbutin in the conjugates with prospective association constants. The inclusion associations of the conjugates with immobilized DXR reached 2.2 x 10(5) approximately 1.4 x 10(8) M(-1). The extremely high inclusion associations for DXR suggested their potential abilities as drug-carrying molecules for carrying DXR. The NMR analyses indicated that the phenyl group of the conjugates greatly served to increase the inclusion associations for DXR. In their DXR inclusion complexes, the formation of the stacking complexes by the pi;-pi interactions between the phenyl groups and the included DXR also enhanced their inclusion abilities for DXR.

  3. Characterization of mitotane (o,p'-DDD)--cyclodextrin inclusion complexes: phase-solubility method and NMR.

    PubMed

    Alfonsi, R; Attivi, D; Astier, A; Socha, M; Morice, S; Gibaud, S

    2013-05-01

    Mitotane (o,p'-dichlorodimethyl dichloroethane [o,p'-DDD]) is used for the treatment of adrenocortical cancer and occasionally Cushing's syndrome. This drug is very poorly soluble in water, and following oral administration, approximately 60% of the dose is recovered in the feces unaltered. The preparation of a soluble formulation (i.e. by complexation with cyclodextrins) with improved bioavailability is the aim of this work. The inclusion of mitotane in methyl-ß-cyclodextrins was studied using both phase-solubility methods and NMR experiments. To elucidate the inclusion mechanism, o,p'-DDD was compared to its regioisomer (i.e. p,p'-DDD). It was demonstrated that two dimethyl-ß-cyclodextrins (DMßCD) can complex with the aromatic rings. From the phase-solubility diagrams, we observe that both cases are very different: K(1:1) is between 37 000 and 85 000 mol.l(-1), whereas K(1:2) is between 5.3 and 32 mol.l(-1). The NMR experiments confirmed the inclusion but it also gave an insight into the kinetics of the dissociation: the ortho-chloro moiety is in slow exchange on the NMR time scale, whereas the para-chloro moiety is in fast exchange rate.

  4. 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.

  5. 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.

  6. Synthesis and spectral investigation of Al(III) catechin/β-cyclodextrin and Al(III) quercetin/β-cyclodextrin inclusion compounds

    NASA Astrophysics Data System (ADS)

    Dias, Karina; Nikolaou, Sofia; De Giovani, Wagner F.

    2008-06-01

    Al-catechin/β-cyclodextrin and Al-quercetin/β-cyclodextrin (β-CD) inclusion compounds were synthesized and characterized by IR, UV-vis, 1H and 13C NMR and TG and DTA analyses. Because quercetin is sparingly soluble in water, the stability constants of the Al-quercetin/β-CD and Al-catechin/β-CD compounds were determined by phase solubility studies. The A L-type diagrams indicated the formation of 1:1 inclusion compounds and allowed calculation of the stability constants. The thermodynamic parameters were obtained from the dependence of the stability constants on temperature and results indicated that the formation of the inclusion compounds is an enthalpically driven process. The thermal decomposition of the solid Al-quercetin/β-CD and Al-catechin/β-CD inclusion compounds took place at different stages, compared with the respective precursors, proving that an inclusion complexation process really occurred.

  7. Encapsulation of tea tree oil by amorphous beta-cyclodextrin powder.

    PubMed

    Shrestha, Meena; Ho, Thao M; Bhandari, Bhesh R

    2017-04-15

    An innovative method to encapsulate tea tree oil (TTO) by direct complexation with solid amorphous beta-cyclodextrin (β-CD) was investigated. A β-CD to TTO ratio of 90.5:9.5 (104.9mg TTO/g β-CD) was used in all complexation methods. The encapsulation was performed by direct mixing, and direct mixing was followed by the addition of water (13-17% moisture content, MC) or absolute ethanol (1:1, 1:2, 1:3 and 1:4 TTO:ethanol). The direct mixing method complexed the lowest amount of TTO (60.77mg TTO/g β-CD). Powder recrystallized using 17% MC included 99.63mg of TTO/g β-CD. The addition of ethanol at 1:2 and 1:3 TTO:ethanol ratios resulted in the inclusion of 94.3 and 98.45mg of TTO/g β-CD respectively, which was similar to that of TTO encapsulated in the conventional paste method (95.56mg TTO/g β-CD), suggesting an effective solid encapsulation method. The XRD and DSC results indicated that the amorphous TTO-β-CD complex was crystallized by the addition of water and ethanol.

  8. Interaction of the noncovalent molecular adapter, beta-cyclodextrin, with the staphylococcal alpha-hemolysin pore.

    PubMed Central

    Gu, L Q; Bayley, H

    2000-01-01

    Cyclodextrins act as noncovalent molecular adapters when lodged in the lumen of the alpha-hemolysin (alphaHL) pore. The adapters act as binding sites for channel blockers, thereby offering a basis for the detection of a variety of organic molecules with alphaHL as a biosensor element. To further such studies, it is important to find conditions under which the dwell time of cyclodextrins in the lumen of the pore is extended. Here, we use single-channel recording to explore the pH- and voltage-dependence of the interaction of beta-cyclodextrin (betaCD) with alphaHL. betaCD can access its binding site only from the trans entrance of pores inserted from the cis side of a bilayer. Analysis of the binding kinetics shows that there is a single binding site for betaCD, with an apparent equilibrium dissociation constant that varies by >100-fold under the conditions explored. The dissociation rate constant for the neutral betaCD molecule varies with pH and voltage, a result that is incompatible with two states of the alphaHL pore, one of high and the other of low affinity. Rather, the data suggest that the actual equilibrium dissociation constant for the alphaHL. betaCD complex varies continuously with the transmembrane potential. PMID:11023901

  9. Incorporation of the sunscreen agent, octyl methoxycinnamate in a cellulosic fabric grafted with beta-cyclodextrin.

    PubMed

    Scalia, Santo; Tursilli, Rosanna; Bianchi, Anna; Nostro, Pierandrea Lo; Bocci, Eugenio; Ridi, Francesca; Baglioni, Piero

    2006-02-03

    The aim of the study was to investigate the incorporation of the sunscreen agent, octyl methoxycinnamate into cyclodextrin cavities covalently bound to cloth fibres. Tencel, a cellulosic fabric, was grafted with beta-cyclodextrin molecules through reaction with monochlorotriazinyl-beta-cyclodextrin (beta-CDMCT). The finished and untreated textiles were soaked in water-methanol mixtures containing 2% (v/v) of sunscreen agent and subsequently subjected to several washing cycles. The unmodified and modified fabrics were characterized by UV spectrophotometry and thermogravimetric analysis. The level of octyl methoxycinnamate entrapped in the Tencel tissue was determined by high-performance liquid chromatography and was found to be much higher (0.0203%, w/w) for the textile functionalised with beta-CDMCT compared to the unmodified fabric (0.0025%, w/w). In addition, spectrophotometric assessment of UV transmission through the fabric samples using the Transpore test showed that the in vitro sun protection factor of the textile support was markedly enhanced (3.2-fold increase) by impregnation with octyl methoxycinnamate of the beta-CDMCT grafted textile. Hence, even after repeated washings, the beta-CD finished fabric exhibits higher sunscreen agent retention and photoprotective properties than the unmodified textile material.

  10. 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.

  11. Nonaqueous synthesis of a selectively modified, highly anionic sulfopropyl ether derivative of cyclomaltoheptaose (beta-cyclodextrin) in the presence of 18-crown-6.

    PubMed

    Kirschner, Daniel L; Green, Thomas K

    2005-08-15

    A highly anionic cyclomaltooligosaccharide (cyclodextrin, CD) derivative containing sulfopropyl functional groups on the primary face of the CD was synthesized. Heptakis(2,3-di-O-methyl)cyclomaltoheptaose [heptakis(2,3-di-O-methyl)-beta-cyclodextrin] was reacted with 1,3-propane sultone and potassium hydride (KH) in anhydrous tetrahydrofuran in the presence of 18-crown-6 to yield highly substituted potassium heptakis(2,3-di-O-methyl-6-O-sulfopropyl)cyclomaltoheptaose [heptakis(KSPDM)-beta-CD] with an average degree of substitution (DSCE) of 6.9 as determined by inverse detection capillary electrophoresis (CE). The principal species in the product is the fully substituted heptakis(KSPDM)-beta-CD. Complete NMR assignments of the hydrogen and carbon atoms are made using a combination of gCOSY and gHSQC. In the absence of 18-crown-6, the reaction generates a mixture of multiply charged derivatives with average DSCE of 4.1. The possible roles of the crown ether in the reaction are discussed. The ROESY NMR spectrum of the inclusion complex that forms between heptakis(KSPDM)-beta-CD and 2-naphthoic acid in D2O reveals that 2-naphthoic acid inserts with the carboxyl group toward the derivatized primary rim of the cyclodextrin.

  12. Investigation of Inclusion Complex of Patchouli Alcohol with β-Cyclodextrin

    PubMed Central

    Wu, Lilan; Qi, Rui; Wu, Yunshan; Li, Yucui; Tang, Lipeng; Guo, De-an; Liu, Bo

    2017-01-01

    The objective of this study was to improve the stability and water-solubility of patchouli alcohol by complexing with β-cyclodextrin (β-CD). The interactions between patchouli alcohol and β-CD were characterized by differential scanning calorimetry (DSC), Fourier transformation-infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and Scanning electron microscope (SEM), respectively. According to molecular modeling method, the enthalpy formation of host-guest illustrated the predominant configuration and the lowest value ΔbGo was -10.8174±1.9235 kcal/mol, suggesting the complex could reduce the energy of the system. The characterization analysis confirmed the formation of PA-CD inclusion complex, and the results indicated the advantage of the inclusion complex in stability and dissolution rates. These results identified PA-CD inclusion complex an effective way for the storage of PA, and better inclusion method still needed to be studied. PMID:28095424

  13. 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.

  14. 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.

  15. 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

  16. Photostabilization of 1,4-dihydropyridine antihypertensives by incorporation into beta-cyclodextrin and liposomes.

    PubMed

    Ragno, G; Risoli, A; Ioele, G; Cione, E; De Luca, M

    2006-01-01

    Inclusion compounds of eleven dihydropyridine drugs were formed and investigated for protection against photo-induced drug degradation. Formulations of cyclodextrins and liposomes were prepared and their photoprotective ability for the encapsulated drug was monitored. Drug photodegradation was spectrophotometrically followed during exposure of the formulations to light of a Xenon lamp. ICH guidelines for photostability testing were applied. A comparison with common pharmaceutical formulations revealed optimal protection for both formulations. The use of the liposome and cyclodextrin inclusion complexes resulted in a mean drug recovery of 77 and more then 90% respectively, after a light exposure until to 30 minutes with an intensity of 21 kJ x min(-1) m(-2). Lercanidipine and Manidipine only did not show a satisfactory increase of photostabilization in the studied supramolecular complexes, due to their low inclusion in both the systems.

  17. 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.

  18. 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.

  19. Non-covalent inclusion of ferulic acid with alpha-cyclodextrin improves photo-stability and delivery: NMR and modeling studies.

    PubMed

    Anselmi, Cecilia; Centini, Marisanna; Maggiore, Maria; Gaggelli, Nicola; Andreassi, Marco; Buonocore, Anna; Beretta, Giangiacomo; Facino, Roberto Maffei

    2008-03-13

    Ferulic acid (FA) is a highly effective antioxidant and photo-protective agent, already approved in Japan as a sunscreen, but it is poorly suited for cosmetic application because of its low physicochemical stability. We prepared the inclusion complex of FA with alpha-cyclodextrin by co-precipitation from an aqueous solution, and used (1)H NMR and molecular dynamics to investigate the most probable structure of the inclusion complex. In rotating frame nuclear Overhouser effect spectroscopy (ROESY) experiments FA penetrated the alpha-CD hydrophobic cavity with the alpha,beta-unsaturated part of the molecule and some of its aromatic skeleton. In proton chemical shift measurements of FA and alpha-cyclodextrins we determined the stoichiometry of the association complex (1:1) by Job's method, and its stability constant (K(1:1) 1162+/-140 M(-1)) and described the molecular dynamics of the complex on the basis of theoretical studies. Encapsulation with alpha-cyclodextrin improves (i) the chemical stability of FA against UVB stress (10 MED [Minimal Erythemal Dose: 1 MED=25 mJ/cm(2) for skin phototype II: 30]), since no degradation products are formed after irradiation, and (ii) the bioavailability of FA on the skin, slowing its delivery (Strainer cell model).

  20. Molecular encapsulation of 5-nitroindazole derivatives in 2,6-dimethyl-beta-cyclodextrin: electrochemical and spectroscopic studies.

    PubMed

    Pérez-Cruz, Fernanda; Jullian, Carolina; Rodriguez, Jorge; Arán, Vicente J; Olea-Azar, Claudio

    2009-07-01

    Four different 5-nitroindazole derivatives (1-4) and its inclusion with Heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DMbetaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes were determined by phase-solubility measurements obtaining in all cases a type-A(L) diagram. Also electrochemical studies were carried out, where the observed change in the E(PC) value indicated a lower feasibility of the nitro group reduction. The same behavior was observed in the ESR studies. The detailed spatial configuration is proposed based on 2D NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data.

  1. Preparation and evaluation of lidocaine hydrochloride in cyclodextrin inclusion complexes for development of stable gel in association with chlorhexidine gluconate for urogenital use

    PubMed Central

    Soares da Silva, Luiz Francisco Jones; do Carmo, Flavia Almada; de Almeida Borges, Vinicius Raphael; Monteiro, Lidiane Mota; Rodrigues, Carlos Rangel; Cabral, Lúcio Mendes; de Sousa, Valeria Pereira

    2011-01-01

    Inclusions of lidocaine hydrochloride in cyclodextrins were prepared to obtain stable complexes compatible for association with chlorhexidine in a new gel formulation for use in urogenital applications. Two cyclodextrins, β-cyclodextrin and methyl-β-cyclodextrin, were used for encapsulating lidocaine hydrochloride through solubilization and kneading techniques. The lidocaine–cyclodextrin complexes were characterized by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The results revealed that the techniques generated good yields of inclusion products that maintained the functional properties of lidocaine. In addition, the inclusion products obtained improved the compatibility of lidocaine hydrochloride with chlorhexidine in solution and a gel formulation. The gel formulation displayed desirable rheological and physicochemical properties. The results presented here are the first description of the inclusion of lidocaine with cyclodextrins, which improves compatibility with chlorhexidine in formulations for simultaneous delivery. PMID:21822378

  2. Complexation of imazalil with beta-cyclodextrin, residue uptake, persistence, and activity against penicillium decay in citrus fruit following postharvest dip treatments.

    PubMed

    Schirra, Mario; Delogu, Giovanna; Cabras, Paolo; Angioni, Alberto; D'hallewin, Guy; Veyrat, Ana; Marcos, Jose F; Candelas, Luis González

    2002-11-06

    A method for the inclusion of imazalil (IMZ) in the beta-cyclodextrin (betaCD), structural characterization of the inclusion complex and its antifungal activity against Penicillium digitatum and P. italicum assessed by in vitro and in vivo tests are reported. According to the starting stoichiometry of betaCD with respect to IMZ, an equimolar ratio beta-cyclodextrin-IMZ (betaCD-IMZ) was detected by (1)H NMR. In vitro assays showed that the freshly prepared betaCD-IMZ was as effective as IMZ, although 1- and 4-day-old betaCD-IMZ mixtures were more effective. Studies on Star Ruby grapefruit showed no significant differences in residue uptake between treatments with an IMZ commercially available fungicide (Deccozil) or betaCD-IMZ when equal active ingredient (a.i.) concentrations (250 mg/L) and dip temperatures (20 or 50 degrees C) were used. By contrast, treatments of Tarocco oranges and Di Massa lemons with 250 mg/L betaCD-IMZ at 50 degrees C produced significant differences in residue uptake in comparison with 250 mg/L Deccozil treatments at 50 degrees C. The a.i. degradation rate in grapefruit during postquarantine and simulated marketing period (SMP) at 20 degrees C was not affected by the type of formulation used, whether at 20 or 50 degrees C. Conversely, IMZ in oranges and lemons had greater persistence when applied at 50 degrees C. All fungicide treatments showed a comparable efficacy against decay in grapefruit and oranges, whereas treatment in lemons at 250 mg/L a.i. of heated fungicides had higher suppressive effects against decay than unheated chemicals having equal a.i. concentrations and comparable activity at 1200 mg/L IMZ at 20 degrees C.

  3. Physicochemical study and characterization of the trimethoprim/2-hydroxypropyl-γ-cyclodextrin inclusion complex

    NASA Astrophysics Data System (ADS)

    Macedo, Osmir F. L.; Andrade, George R. S.; Conegero, Leila S.; Barreto, Ledjane S.; Costa, Nivan B., Jr.; Gimenez, Iara F.; Almeida, Luis E.; Kubota, Daniela

    2012-02-01

    Here we report the preparation of a trimethoprim/2-hydroxypropyl-γ-cyclodextrin inclusion complex along with a physicochemical study, structural characterization, and molecular modeling of the complex. As main results, we observed from phase-solubility studies at two temperatures (20 °C and 35 °C) that the association constants decrease with increasing temperature. Values for K1:1 constant were of the same magnitude order of those found for the parent γ-CD. The inclusion orientation as evidenced by ROESY measurements involves the inclusion of the 3,4,5-trimethoxybenzyl ring in the CD cavity from the larger rim. This is in agreement with semiempirical molecular modeling calculation.

  4. 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

  5. Supramolecular aggregates formed by sulfadiazine and sulfisomidine inclusion complexes with α- and β-cyclodextrins.

    PubMed

    Rajendiran, N; Venkatesh, G; Saravanan, J

    2014-08-14

    Sulfadiazine (SDA) and sulfisomidine (SFM) inclusion complexes with two cyclodextrins (α-CD and β-CD) are studied in aqueous as well as in solid state. The inclusion complexes are characterized by UV-visible, fluorescence, time correlated single photon counting, FTIR, DSC, PXRD and (1)H NMR techniques. The self assembled SDA/CD and SFM/CD inclusion complexes form different types of nano and microstructures. The self assembled nanoparticle morphologies are studied using SEM and TEM techniques. SDA/α-CD complex is formed hierarchal morphology, SDA/β-CD and SFM/β-CD complexes form the nanosheet self assembly. However, SFM/α-CD complex forms nanoporous sheet self assembly. van der Waals, hydrophobic and hydrogen bonding interaction play a vital role in the self assembling process.

  6. Dissolution behavior of β-cyclodextrin molecular inclusion complexes of aceclofenac

    PubMed Central

    Dua, Kamal; Pabreja, Kavita; Ramana, M. V.; Lather, Vinny

    2011-01-01

    The objective of the present investigation was to study the effect of β-cyclodextrin (β-CD) on the in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. Aceclofenac molecular inclusion complexes in 1:1 and 1:2 M ratio were prepared using a kneading method. The in vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes was carried out. Molecular inclusion complexes of AF with β-CD showed a considerable increase in the dissolution rate in comparison with the physical mixture and pure drug in 0.1 N HCl, pH 1.2, and phosphate buffer, pH 7.4. Inclusion complexes with a 1:2 M ratio showed the maximum dissolution rate in comparison to other ratios. Fourier transform infrared spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and β-CD in complexes in solid state. Molecular modeling results indicated the relative energetic stability of the β-CD dimer-AF complex as compared to β-CD monomer-AF. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with β-CD. The in vitro release from all the formulations was best described by first-order kinetics (R2 = 0.9826 and 0.9938 in 0.1 N HCl and phosphate buffer, respectively) followed by the Higuchi release model (R2 = 0.9542 and 0.9686 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, the dissolution of AF can be enhanced by the use of a hydrophilic carrier like β-CD. PMID:21966164

  7. Ethylenediaminetetraacetic acid (EDTA) as an auxiliary tool in the electrospray ionization mass spectrometry analysis of native and derivatized beta-cyclodextrins, maltoses, and fructans contaminated with Ca and/or Mg.

    PubMed

    Giudicessi, Silvana L; Fatema, M Kaniz; Nonami, Hiroshi; Erra-Balsells, Rosa

    2010-09-01

    The effect of Ca(2+) (and Mg(2+)) and the disodium salt of ethylenediaminetetraacetic acid (EDTA), a well known Ca(2+) (and Mg(2+)) chelating agent, on the volatilization/ionization of carbohydrates by using electrospray ionization mass spectrometry has been studied. Model compounds such as maltoses (maltose to maltoheptaose), beta-cyclodextrins (beta-cyclodextrin, methyl-beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin, and 2-hydroxypropyl-beta-cyclodextrin) and fructans (sucrose, 1-ketose, nystose, and 1F-fructofuranosylnystose) were used.

  8. Stabilization of thymopentin and preservation of its pharmacological properties by 2-hydroxypropyl-beta-cyclodextrin.

    PubMed

    Brown, N D; Butler, D L; Chiang, P K

    1993-07-01

    Thymopentin prepared in 5, 15, and 20% 2-hydroxypropyl-beta-cyclodextrin (HPCD) was able to inhibit guinea-pig ileum contraction stimulated by anatoxin-a (3 x 10(-6) M) after fourteen months of storage at room temperature. Thus, in contrast to the instability of thymopentin prepared without HPCD, the pharmacological activity was retained and could be stored in a ready-to-use solution for extended periods without refrigeration.

  9. Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis.

    PubMed

    Rodgers, Jean; Jones, Amy; Gibaud, Stéphane; Bradley, Barbara; McCabe, Christopher; Barrett, Michael P; Gettinby, George; Kennedy, Peter G E

    2011-09-01

    Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites Trypanosoma brucei (T. b.) gambiense or T. b. rhodesiense and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage T. b. rhodesiense infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-β-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties in vitro and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy.

  10. Conformation for a beta-cyclodextrin monosubstituted with a cyclic dipeptide.

    PubMed Central

    Di Blasio, B; Pavone, V; Nastri, F; Isernia, C; Saviano, M; Pedone, C; Cucinotta, V; Impellizzeri, G; Rizzarelli, E; Vecchio, G

    1992-01-01

    The structural characterization of a beta-cyclodextrin monosubstituted with the peptide cyclo(L-His-L-Leu) is reported. This work provides an x-ray example of a covalently bound group that folds in such a way that the terminal apolar side chain is retained in the hydrophobic interior of the cone-shaped cyclodextrin cavity. 6-Deoxy-6-cyclo(L-histidyl-L-leucyl)-beta-cyclodextrin crystallizes in the space group P1 with cell dimensions a = 14.728(8) A, b = 15.084(7) A, c = 18.182(10) A, alpha = 94.36(6) degrees, beta = 95.81(5) degrees, gamma = 116.08(9) degrees; overall isotropic agreement R = 10.6% for 5703 observed reflections (Fo greater than 3 sigma). The molecular structure consists of two independent molecules with the formula C54H86N4O36.7.25H2O. Each molecule assumes a "sleeping swan"-like overall shape with the hydrophobic leucine side chain inserted inside the cavity of the macrocycle. The two independent units give rise to a head-to-tail dimer linked by hydrogen bonds occurring between primary and secondary hydroxyl groups of the two monomers. The packing of the dimers produces cavities containing water molecules. There are infinite hydrophilic channels running in the crystal, which is similar to what is found in the structures of cyclic peptides. PMID:1496014

  11. "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.

  12. Spectroscopic study on the inclusion complexes of β-cyclodextrin with selected metabolites of catecholamines

    NASA Astrophysics Data System (ADS)

    Korytkowska-Wałach, Anna; Dubrawska, Beata; Śmiga-Matuszowicz, Monika; Bieg, Tadeusz

    2017-01-01

    Inclusion complexes formed between β-cyclodextrin (β-CD) and metabolites of catecholamines, i.e. vanillylmandelic acid (VMA), homovanillic acid (HVA) as well as vanillin (VA) were studied using NMR spectroscopy. Due to the importance of these compounds for the diagnosis tumours of the sympathoadrenal system, hydrogels containing β-CD moieties for enhancing entrapping metabolites of catecholamine from aqueous solutions are located in the area of our interest. Stoichiometry and association constants of the complexes of β-CD with VMA, HVA and VA respectively were determined by using continuous variation and 1H NMR titration methods. Significant discrepancies were pointed out depending on used referencing method. In this study water solution of 3-(trimethylsilyl)propionic-2,2,3,3-d4 acid sodium salt as an external reference was used to avoid errors in the determination of association constants. β-CD formed the most stable complexes with VA and HVA molecules whilst smallest value of association constant was determined for the VMA/β-CD complex. Two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY) allowed to establish definite information on the molecular structures of the complexes formed. Geometry of the latter was proposed basing on contour plots of the 2D ROESY spectra, which also indicated two possibilities of complexed molecule arrangement into β-cyclodextrin interior. The values of determined association constants are in good agreement with postulated geometry of the complexes. Value of association constant determined for inclusion complexes of β-cyclodextrin with homovanillic acid an vanillin indicates the strongest binding of molecules among investigated complexes, so it was finally concluded that β-CD moiety introduced into hydrogel network could be effective for homovanillic acid and vanillin entrapping.

  13. Assembly of beta-cyclodextrin with 3S-tetrahydro-beta-carboline-3-carboxylic acid and self-assembly of 6-(3'S-carboline-3'-carboxylaminoethylamino)-6-deoxy-beta-cyclodextrin: approaches to enhance anti-oxidation stability and anti-thrombotic potency.

    PubMed

    Li, Li; Cui, Guohui; Zhao, Ming; Wang, Yuji; Wang, Hong; Li, Wei; Peng, Shiqi

    2008-09-25

    3 S-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid (THCA) isolated from Bulbus allii macrostemi was identified as the active antiplatelet aggregation ingredient. However, the very poor water solubility and the shortcoming of being oxidized easily in vivo seriously limit the clinical application of THCA. In the present study, two strategies were used to reduce this tendency. First, the inclusion complex of THCA with beta-cyclodextrin (beta-CD) was prepared. Spectral studies identified that the inclusion complex (beta-CD1,2/THCA) was in equilibrium between beta-CD/THCA and beta-CD2/THCA, and the proportion of two isomers was beta-CD concentration dependent; it was 89% vs 11% in our study. The oxidation of both THCA and beta-CD1,2/THCA by H2O2 followed first-order kinetics, and 35% of THCA and 33% of beta-CD1,2/THCA were oxidized during the monitoring period. In vitro antiplatelet aggregation and in vivo oral administration antithrombotic activity of THCA was largely increased via inclusion complexation with beta-CD. Second, a novel conjugate 6-(3' S-carboline-3'-carboxyamino-ethylamino)-6-deoxy-beta-CD (5-monomer) was prepared. Spectral characterizations demonstrated that 5-monomer was able to self-assemble into 5-dimer, which was coexisting with the monomer with a ratio of 79% vs 21% in solution. The in vitro oxidation of 5-monomer/5-dimer by H2O2 did not occur during the monitoring period. The in vitro antiplatelet aggregation and in vivo antithrombotic assays of 5-monomer /5-dimer demonstrated that the bioactivity of THCA was remarkably increased via conjugation with 6-ethylamino-6-deoxy-beta-CD and produced greater in vitro and in vivo effectiveness than that of the inclusion complex beta-CD1,2/THCA at the same dose. The significant improvement of the bioactivity and stability of THCA indicates that inclusion complexation and conjugation with beta-CD provide promising approaches to improve the practical use of THCA in clinical applications.

  14. Improved Pharmacokinetics of Aceclofenac Immediate Release Tablets Incorporating its Inclusion Complex with Hydroxypropyl-β-Cyclodextrin.

    PubMed

    Dahiya, Sunita; Kaushik, Atul; Pathak, Kamla

    2015-01-01

    The present investigation reports the various pharmacokinetic parameters of immediate release aceclofenac tablets incorporating its inclusion complex with hydroxypropyl-β-cyclodextrin. The tablets were prepared using aceclofenac: hydroxypropyl-β-cyclodextrin in a 1:1 molar ratio by the direct compression method (TKN). The results were compared with those of the marketed brand (MKT) and pure drug (TAC). The P-values indicated that mean plasma concentrations were significantly different among all three formulations administered (P<0.05, P<0.01). TKN showed significantly higher plasma levels when compared to the pure drug (P<0.01). The Cmax and AUC(0-∞) of TKN were significantly higher (P<0.05) compared to the pure drug and marketed formulation. Furthermore, the first-order overall elimination rate constant (Kel) of TKN was also significantly higher (P<0.05) compared to the pure drug and its marketed formulation. These results suggested that tablets prepared by incorporating the AC-HPβCD inclusion complex (TKN) would provide a more rapid onset of pharmacological effects in comparison to the marketed formulation and pure drug.

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

    PubMed

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

    2016-03-28

    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.

  16. Inclusion complex thermodynamics: The β-cyclodextrin and sertraline complex example.

    PubMed

    Lopes, Juliana Fedoce; Nascimento, Clebio S; Anconi, Cleber P A; Dos Santos, Hélio F; De Almeida, Wagner B

    2015-11-01

    Thermodynamic properties for β-cyclodextrin-Sertraline inclusion process was calculated at the density functional theory (DFT) level using the PBE0 functional with 6-31G(d,p), 6-31++G(d,p) and 6-311++G(2df,p) basis sets. Electron correlation was evaluated through Møller-Plesset second-order perturbation theory (MP2). The standard statistical thermodynamic approach was used to assess the entropic contribution to the Gibbs free energy value. According to our results, inclusion of hydration waters to describe the reactants and products in the complex formation reaction model is crucial in order to reproduce the experimental data and seems very coherent with basics thermodynamics yielding good agreement with experiment.

  17. Secondary structure characterization of beta-lactamase inclusion bodies.

    PubMed

    Przybycien, T M; Dunn, J P; Valax, P; Georgiou, G

    1994-01-01

    The secondary structure of proteins in E. coli inclusion bodies was investigated via Raman spectroscopy. Inclusion bodies were purified from cells expressing different forms of RTEM beta-lactamase and grown at either 37 or 42 degrees C. All of the solid phase inclusion body samples examined gave amide I band spectra that were perturbed from that of the native, purified protein in both solution and powder forms; secondary structure estimates indicated significant decreases in alpha-helix and increases in beta-sheet contents in the inclusion body samples. The structure estimates for inclusion bodies isolated from 37 degrees C cultures were similar, regardless of aggregate localization in the E. coli cytoplasmic or periplasmic spaces or beta-lactamase precursor content. Inclusion bodies obtained from 42 degrees C cells exhibited a further reduction of alpha-helix and augmentation of beta-sheet contents relative to those from 37 degrees C cultures. These results are consistent with the paradigm for inclusion body formation via the self-association of intra-cellular folding intermediates having extensive secondary structure content. Further, the overall secondary structure content of inclusion bodies is not significantly affected by subcellular compartmentalization, but may be altered at increased temperatures.

  18. Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules

    PubMed Central

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

    2016-01-01

    Host–guest inclusion complexes of β-cyclodextrin with two vitamins viz., nicotinic acid and ascorbic acid in aqueous medium have been explored by reliable spectroscopic, physicochemical and calorimetric methods as stabilizer, carrier and regulatory releaser of the guest molecules. Job’s plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host-guest assembly. Stereo-chemical nature of the inclusion complexes has been explained by 2D NMR spectroscopy. Surface tension and conductivity studies further support the inclusion process. Association constants for the vitamin-β-CD inclusion complexes have been calculated by UV-visible spectroscopy using both Benesi–Hildebrand method and non-linear programme, while the thermodynamic parameters have been estimated with the help of van’t Hoff equation. Isothermal titration calorimetric studies have been performed to determine the stoichiometry, association constant and thermodynamic parameters with high accuracy. The outcomes reveal that there is a drop in ΔSo, which is overcome by higher negative value of ΔHo, making the overall inclusion process thermodynamically favorable. The association constant is found to be higher for ascorbic acid than that for nicotinic acid, which has been explained on the basis of their molecular structures. PMID:27762346

  19. 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.

  20. Study of production and pyrolysis characteristics of sweet orange flavor-β-cyclodextrin inclusion complex.

    PubMed

    Zhu, Guangyong; Xiao, Zuobing; Zhou, Rujun; Zhu, Yalun

    2014-05-25

    Flavor plays an important role and has been widely used in foods. Encapsulation can prevent the loss of volatile aromatic ingredients, provide protection and enhance the stability of the flavor. Kinetic and thermodynamic parameters are helpful in understanding the mechanism of molecular recognition between hosts and guests. This work focused on the study of production of a sweet orange flavor-β-cyclodextrin (CD) inclusion complex, and investigated the combination of flavor and β-CD by thermogravimetric analysis. Pyrolysis characteristics, kinetic and thermodynamic parameters of the flavor-β-CD inclusion complex were determined. The results showed that the flavor-β-CD inclusion complexes can form large aggregates in water. During thermal degradation of blank β-CD and flavor-β-CD inclusion complex, three main stages can be distinguished. The thermogravimetric (TG) curve of blank β-CD shows a leveling-off from room temperature to 250°C, while the TG curve of flavor-β-CD inclusion complex is downward sloping in this temperature range.

  1. 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.

  2. Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    Host–guest inclusion complexes of β-cyclodextrin with two vitamins viz., nicotinic acid and ascorbic acid in aqueous medium have been explored by reliable spectroscopic, physicochemical and calorimetric methods as stabilizer, carrier and regulatory releaser of the guest molecules. Job’s plots have been drawn by UV-visible spectroscopy to confirm the 1:1 stoichiometry of the host-guest assembly. Stereo-chemical nature of the inclusion complexes has been explained by 2D NMR spectroscopy. Surface tension and conductivity studies further support the inclusion process. Association constants for the vitamin-β-CD inclusion complexes have been calculated by UV-visible spectroscopy using both Benesi–Hildebrand method and non-linear programme, while the thermodynamic parameters have been estimated with the help of van’t Hoff equation. Isothermal titration calorimetric studies have been performed to determine the stoichiometry, association constant and thermodynamic parameters with high accuracy. The outcomes reveal that there is a drop in ΔSo, which is overcome by higher negative value of ΔHo, making the overall inclusion process thermodynamically favorable. The association constant is found to be higher for ascorbic acid than that for nicotinic acid, which has been explained on the basis of their molecular structures.

  3. Functional properties of cholesterol-removed whipping cream treated by beta-cyclodextrin.

    PubMed

    Shim, S Y; Ahn, J; Kwak, H S

    2003-09-01

    The present study was carried out to examine the changes in functional properties of cholesterol-removed whipping cream by beta-cyclodextrin (beta-CD) treatment. The cholesterol removal rate reached over 90% in cream before whipping in all conditions (different stirring time and speed) applied. The apparent viscosity of beta-CD treated cream after whipping increased with increased stirring time and speed. Comparatively, the overrun percentage reached to 150%, and foam instability was measured as 2.5 ml deformed cream with lower stirring time (10 min) and speed (400 rpm). The thiobarbituric acid value of cholesterol-removed whipping cream increased from 0.08 to 0.14 stored at 4 degrees C during 4 wk; however, no difference was found compared with that of control. Above results indicated that beta-CD treatment process for cholesterol removal did not show a profound adverse effect on functional properties of cream after whipping.

  4. Clonidine complexation with hydroxypropyl-beta-cyclodextrin: From physico-chemical characterization to in vivo adjuvant effect in local anesthesia.

    PubMed

    Braga, M A; Martini, M F; Pickholz, M; Yokaichiya, F; Franco, M K D; Cabeça, L F; Guilherme, V A; Silva, C M G; Limia, C E G; de Paula, E

    2016-02-05

    Clonidine (CND), an alpha-2-adrenergic agonist, is used as an adjuvant with local anesthetics. In this work, we describe the preparation and characterization of an inclusion complex of clonidine in hydroxypropyl-beta-cyclodextrin (HP-β-CD), as revealed by experimental (UV-vis absorption, SEM, X-ray diffraction, DOSY- and ROESY-NMR) and theoretical (molecular dynamics) approaches. CND was found to bind to HP-β-CD (Ka=20M(-1)) in 1:1 stoichiometry. X-ray diffractograms and SEM images provided evidence of inclusion complex formation, which was associated with changes in the diffraction patterns of the pure compounds. NMR experiments revealed changes in the chemical shift of H3HP-β-CD hydrogens (Δ=0.026ppm) that were compatible with the insertion of CND in the hydrophobic cavity of the cyclodextrin. Molecular dynamics simulation with the three CND species that exist at pH 7.4 revealed the formation of intermolecular hydrogen bonds, especially for the neutral imino form of CND, which favored its insertion in the HP-β-CD cavity. In vitro assays revealed that complexation retarded drug diffusion without changing the intrinsic toxicity of clonidine, while in vivo tests in rats showed enhanced sensory blockade after the administration of 0.15% CND, with the effect decreasing in the order: CND:HP-β-CD+bupivacaine>CND+bupivacaine>bupivacaine>CND:HP-β-CD>clonidine. The findings demonstrated the suitability of the complex for use as a drug delivery system for clinical use in antinociceptive procedures, in association with local anesthetics.

  5. Carbonaceous nanofiber membrane functionalized by beta-cyclodextrins for molecular filtration.

    PubMed

    Chen, Ping; Liang, Hai-Wei; Lv, Xiao-Han; Zhu, Hai-Zhou; Yao, Hong-Bin; Yu, Shu-Hong

    2011-07-26

    In this paper, we report the fabrication of carbonaceous nanofiber (CNF) membranes functionalized by beta-cyclodextrins (CNF-β-CD membrane) and their application for molecular filtration. The chemically synthesized carbonaceous nanofibers were first functionalized by β-CD, and the free-standing CNF membrane can be prepared by a simple filtration process. The membrane shows a remarkable capability to function as an ideal molecular filter through complexation of phenolphthalein molecules with the cyclodextrin molecules grafted on the CNFs. As a typical dye pollutant, fuchsin acid can also be effectively removed from the solution through such a membrane. Engineering the surface of this carbonaceous nanofiber membrane may allow it to be used for other applications such as chiral separation and drug delivery.

  6. Inclusion compounds of dibenzylthiourea with hydroxypropylated-cyclodextrins for corrosion protection of carbon steel in acidic medium

    NASA Astrophysics Data System (ADS)

    de Souza, Thais M.; Cordeiro, Renata F. B.; Viana, Gil M.; Aguiar, Lucia C. S.; de Senna, Lilian F.; Malta, Luiz Fernando B.; D'Elia, Eliane

    2016-12-01

    In this work the complexation of the guest molecule (dibenzylthiourea-DBT) with α and β forms of hydroxypropylated cyclodextrins was evaluated in solution and in the solid state by different techniques. It was shown that the inclusion complexes were obtained and the aromatic moieties of DBT are points of interaction in the structure of the guest. The inhibitory action of these inclusion compounds in carbon steel corrosion in acidic medium was evaluated by polarization curves, electrochemical impedance diagrams and weight loss measurements. There is an enhancement of the inhibitory action against the carbon steel corrosion in HCl solution when the DBT was encapsulated in inclusion compounds whereas the alone hydroxypropylated cyclodextrins did not present an inhibitory effect. It was concluded that these inclusion compounds could be a good alternative to introduce molecules with low solubility in aqueous media and still increase their inhibitory action.

  7. 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.

  8. 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.

  9. β-Cyclodextrin Inclusion Complex to Improve Physicochemical Properties of Pipemidic Acid: Characterization and Bioactivity Evaluation

    PubMed Central

    Iacovino, Rosa; Rapuano, Filomena; Caso, Jolanda Valentina; Russo, Agostino; Lavorgna, Margherita; Russo, Chiara; Isidori, Marina; Russo, Luigi; Malgieri, Gaetano; Isernia, Carla

    2013-01-01

    The aptitude of cyclodextrins (CDs) to form host-guest complexes has prompted an increase in the development of new drug formulations. In this study, the inclusion complexes of pipemidic acid (HPPA), a therapeutic agent for urinary tract infections, with native β-CD were prepared in solid state by kneading method and confirmed by FT-IR and 1H NMR. The inclusion complex formation was also characterized in aqueous solution at different pH via UV-Vis titration and phase solubility studies obtaining the stability constant. The 1:1 stoichiometry was established by a Job plot and the inclusion mechanism was clarified using docking experiments. Finally, the antibacterial activity of HPPA and its inclusion complex was tested on P. aeruginosa, E. coli and S. aureus to determine the respective EC50s and EC90s. The results showed that the antibacterial activity of HPPA:β-CD against E. coli and S. aureus is higher than that of HPPA. Furthermore, HPPA and HPPA:β-CD, tested on human hepatoblastoma HepG2 and MCF-7 cell lines by MTT assay, exhibited, for the first time, antitumor activities, and the complex revealed a higher activity than that of HPPA. The use of β-CD allows an increase in the aqueous solubility of the drug, its bioavailability and then its bioactivity. PMID:23799358

  10. Monolayer kinetic model of formation of β-cyclodextrin-β-carotene inclusion complex.

    PubMed

    Ivanova, Tz; Mircheva, K; Balashev, K; Panaiotov, I; Boury, F

    2015-11-01

    The carotenoids are sensitive molecules and their chemical integrity must be preserved from pro-oxidant elements which could affect and decrease their physiological benefits. The encapsulation based on the inclusion of the carotenoids into cage molecules is a promising approach for preserving over time of the intrinsic properties of the carotenoids. It is well known that cyclic oligosaccharide β-cyclodextrin (CD) as a cage molecule possesses strong inclusion ability to β-carotene (C) and as a result of the hydrophobic interactions forms an inclusion complex. In the present paper a monolayer kinetic model was established with the notion to extract more information about the influence of the molecular structure and organization to the interfacial interactions between the interacting species as well as about the role of the specific areas, which are often underestimated in previously studied dispersed systems. We developed the monolayer kinetic model for the formation of the inclusion CD-C complex by applying an experimental approach for following the kinetics by means of measuring the decrease of the surface area (ΔA) versus time (t) at constant surface pressure (π) and the decrease of surface pressure (π) versus time (t) at constant surface area (A). We also visualized by AFM the state of the monolayers at the initial and end points of the kinetic process. The values for the degree (d) and constant (Ka) of the association were estimated and compared with those from the studies of dispersed systems.

  11. Preparation, Characterization and Pharmacokinetic Study of Xiangfu Siwu Decoction Essential Oil/β-Cyclodextrin Inclusion Complex.

    PubMed

    Xi, Junzuan; Qian, Dawei; Duan, Jinao; Liu, Pei; Zhu, Zhenhua; Guo, Jianming; Zhang, Yang; Pan, Ying

    2015-06-10

    Xiang-Fu-Si-Wu Decoction (XFSWD), a famous Chinese herbal formula, is considered an effective prescription for treating primary dysmenorrhea. The essential oil is a significant effective ingredient of XFSWD. However, its volatility, instability and poor water-solubility influence its pharmacodynamic effects. β-Cyclodextrin (β-CD) has the intrinsic ability to form specific inclusion complexes with such drugs to enhance their stability, solubility and bioavailability. The aim of this study was thus to compare the pharmacokinetic characteristics and the oral bioavailability of XFSWD essential oil (XEO) and its β-CD inclusion complex after oral administration to rats. A simple, rapid, and sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous quantification of five active components of XEO in rat plasma. The in vivo data showed that XEO/β-CD inclusion complex displayed higher maximum plasma concentration (Cmax), longer half-time (T1/2) and bigger area under the concentration-time curve (AUC0-24 h). These results demonstrated that the formation of β-CD inclusion complex has significantly increased the oral bioavailability of the drugs in rats than free oil.

  12. Characterization of physicochemical properties of naproxen systems with amorphous beta-cyclodextrin-epichlorohydrin polymers.

    PubMed

    Mura, P; Faucci, M T; Maestrelli, F; Furlanetto, S; Pinzauti, S

    2002-08-01

    Ground mixtures of naproxen with amorphous beta-cyclodextrin-epichlorohydrin soluble (betaCd-EPS) or insoluble cross-linked (betaCd-EPI) polymers were investigated for both solid phase characterization (Differential Scanning Calorimetry, powder X-ray Diffractometry) and dissolution properties (dispersed amount method). The effect of different grinding conditions and of drug-to-carrier ratio was also evaluated. Co-grinding induced a decrease in drug crystallinity to an extent which depended on the grinding time, and was most pronounced for the cross-linked insoluble polymer, particularly in combinations at the lowest drug content. Both cyclodextrin polymers were more effective in improving the naproxen dissolution properties, not only than the parent betaCd but also than hydroxyalkyl-derivatives, and their performance was almost comparable to that of methyl-derivatives, previously found as the best carriers for naproxen. Dissolution efficiencies of naproxen from physical mixtures with betaCd-EPS, thanks to the high water solubility of this Cd-derivative, were up to three times higher than those from the corresponding products with betaCd-EPI. However this difference in their performance became much less evident in co-ground products and tended to progressively diminish with increasing the polymer content in the mixture, according to the better amorphizing power shown by betaCd-EPI during the co-grinding process. The 10/90 (w/w) drug-carrier co-ground products exhibited the best dissolution properties, giving dissolution efficiencies about 30 times higher than that of naproxen alone.

  13. Electrokinetic movement of hexachlorobenzene in clayed soils enhanced by Tween 80 and beta-cyclodextrin.

    PubMed

    Yuan, Songhu; Tian, Meng; Lu, Xiaohua

    2006-09-21

    This study describes the comparative behavior of hexachlorobenzene (HCB) contaminated clayed soils in an electrokinetic (EK) system enhanced by Tween 80 and beta-cyclodextrin (beta-CD). The pH of the soils was controlled by Na2CO3/NaHCO3 buffer. Negligible HCB movement was observed when NaOH or Na2CO3/NaHCO3 buffer was used as anodic flushing solution. While Tween 80 or beta-CD was introduced to Na2CO3/NaHCO3 buffer, obvious HCB movement was achieved. Although beta-CD led to a less desorption of HCB from kaolin than Tween 80, the removal of HCB with beta-CD was much higher than that with Tween 80 in the EK system. Tween 80 could be sorped by kaolin more than beta-CD, which was responsible for the result. The mechanism of the movement of HCB was proposed as the enhanced desorption of HCB from soil, the dissolving of HCB in the soil pore fluid and the movement of HCB with the electroosmotic flow. Obvious movement of HCB was also observed in the EK treatment of real HCB-contaminated clayed soil enhanced by beta-CD. It is an alternative approach to use facilitating agents such as beta-CD to enhance the EK movement of HCB in the contaminated clayed soils.

  14. 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.

  15. Benznidazole drug delivery by binary and multicomponent inclusion complexes using cyclodextrins and polymers.

    PubMed

    Soares-Sobrinho, José L; Santos, Fabiana L A; Lyra, Magaly A M; Alves, Lariza D S; Rolim, Larissa A; Lima, Adley A N; Nunes, Lívio C C; Soares, Monica F R; Rolim-Neto, Pedro J; Torres-Labandeira, Juan J

    2012-06-20

    Benznidazole (BNZ) is the drug of choice for Chagas disease treatment, which affects about 9.8 million people worldwide. It has low solubility and high toxicity. The present study aimed to develop and characterize inclusion complexes (IC) in binary systems (BS) with BNZ and randomly methylated-β-cyclodextrin (RMβCD) and in ternary systems (TS) with BNZ, RMβCD and hydrophilic polymers. The results showed that the solid BS had a large increase in dissolution rate (Q>80%). For the solid IC obtained, the kneading method, in ratio of 1:0.17 (77.8% in 60 min), appeared to be the most suitable for the development of a solid oral pharmaceutical product, with possible industrial scale-up and low concentration of CD. The solid TS containing 0.1% of hydroxypropylmethylcellulose (HPMC) showed no significant advantages compared to the binary IC in solid state. The use of cyclodextrins proved to be a viable tool for effective, standardized and safe drug delivery.

  16. Spectroscopic characterization of both aqueous and solid-state diacerhein/hydroxypropyl-β-cyclodextrin inclusion complexes

    NASA Astrophysics Data System (ADS)

    Petralito, Stefania; Zanardi, Iacopo; Spera, Romina; Memoli, Adriana; Travagli, Valter

    2014-06-01

    Diacerhein, a poorly water soluble antirheumatic prodrug, was spectroscopically characterized to form inclusion complexes with hydroxypropyl-β-cyclodextrin (HPβCD) in both aqueous solution and in solid phase. Complexation with the hydrophilic carriers was used to improve the solubility and dissolution rate of the compound. The kinetics of the prodrug degradation to the active rhein in aqueous buffer solution were also investigated as a function of HPβCD concentration. The solid complexes prepared by different methods such as physical mixture, kneading, co-evaporation method and freeze dried method in 1:1 M ratio, were characterized by DSC and FTIR. The dissolution profiles of solid complexes were determined and compared with diacerhein alone and their physical mixture, in the simulated intestinal fluid at 37 °C. The accurate molecular spectroscopic characterization of diacerhein in the presence of different amounts of aqueous cyclodextrins was essential to determine the correct binding constants for the diacerhein/HPβCD system. The binding constants were also validated by UV spectrometry and HPLC procedure in order to compare the values from the different methods. Higuchi-Connors phase solubility method has proved not suitable when either the free or/and the complexed prodrug degrade in aqueous solution.

  17. Identification of ROS produced by photodynamic activity of chlorophyll/cyclodextrin inclusion complexes.

    PubMed

    Cellamare, Barbara M; Fini, Paola; Agostiano, Angela; Sortino, Salvatore; Cosma, Pinalysa

    2013-01-01

    Photodynamic therapy (PDT) is a way of treating malignant tumors and hyperproliferative diseases. It is based on the use of photosensitizer, herein the chlorophyll a (chl a), and a light of an appropriate wavelength. The interaction of the photosensitizer (PS) with the light produces reactive oxygen species (ROS), powerful oxidizing agents, which cause critical damage to the tissue. To solubilize chl a in aqueous solution and to obtain it as monomer, we have used cyclodextrins, carriers which are able to interact with the pigment and form the inclusion complex. The aim of this study is to examine which types of ROS are formed by Chl a/cyclodextrin complexes in phosphate buffered solution and cell culture medium, using specific molecules, called primary acceptors, which react selectively with the reactive species. In fact the changes of the absorption and the emission spectra of these molecules after the illumination of the PS provide information on the specific ROS formation. The (1) O2 formation has been tested using chemical methods based on the use of Uric Acid (UA), 9,10-diphenilanthracene (DPA) and Singlet oxygen sensor green (SOSG) and by direct detection of Singlet Oxygen ((1) O2 ) luminescence decay at 1270 nm. Moreover, 2,7-dichlorofluorescin and ferricytochrome c (Cyt Fe(3+) ) have been used to detect the formation of hydrogen peroxide and superoxide radical anion, which reduces Fe(3+) of the ferricytochrome to Fe(2+) , respectively.

  18. 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.

  19. Evaluation of piroxicam-beta-cyclodextrin, piroxicam, paracetamol and placebo in post-operative oral surgery pain.

    PubMed

    Dolci, G; Ripari, M; Pacifici, L; Umile, A

    1994-01-01

    Two hundred ninety-eight patients with post-operative pain after the surgical removal of an impacted third molar were randomly assigned, on a double-blind basis, to receive a single oral dose of piroxicam 20 mg, or piroxicam-beta-cyclodextrin equivalent to 20 mg piroxicam, or paracetamol 500 mg, or placebo. Using a semi-quantitative self-rating scale, patients rated their pain and its relief at 30-min intervals for the first 2 h, and then hourly for 4 h after treatment administration. All active medications were reported to be significantly superior to placebo. The three active drugs were comparable for the degree of analgesia up to the third hour, after which the effect of paracetamol decreased significantly as compared to piroxicam-beta-cyclodextrin and piroxicam. Piroxicam-beta-cyclodextrin and paracetamol were more rapid than piroxicam in inducing analgesia. The tolerability for the active drugs was comparable to that for placebo.

  20. 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.

  1. Study on the interaction of uranyl with sulfated beta-cyclodextrin by affinity capillary electrophoresis and molecular dynamics simulation.

    PubMed

    Li, Linnan; Zhang, Yiding; Li, Xianjiang; Shen, Sensen; Huang, Hexiang; Bai, Yu; Liu, Huwei

    2016-10-01

    The study on sulfated beta-cyclodextrin binding to uranyl ion helps to get a better understanding of uranyl compounds' intermolecular interaction mechanism and facilitates the structure-based design of uranyl binding molecules. Here we investigated the electromigration of the inclusion complex by using affinity capillary electrophoresis in acidic solution. The binding constant was determined to be logK = 2.96 ± 0.02 (R(2) = 0.996) through nonlinear regression approach. The possible configurations and structural features of the inclusion complex were further studied by molecular dynamics simulation. The results suggest the distinctions of coordination environment and hydration compared with bare uranyl ion in aqueous solution. Thus, two water oxygen atoms coordinated with uranyl in the first hydration shell at 2.55 angstrom instead of five in the same distance range. The binding free energy was calculated as -12.10 ± 1.46 kcal/mol by means of thermodynamic perturbation method. The negative value indicates that the process of S-β-CD capture uranyl ion in the aqueous media is spontaneous.

  2. 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.

  3. beta-Cyclodextrin hydrogels containing naphthaleneacetic acid for pH-sensitive release.

    PubMed

    Yang, Xia; Kim, Jin-Chul

    2010-06-01

    beta-Cyclodextrin (beta-CD) hydrogel was prepared in a strong alkali condition using epichlorohydrin (EPI) as a cross-linker, where the molar ratios of EPI to beta-CD were 8:1, 10:1, and 15:1. In order to endow a pH sensitivity to the hydrogel, naphthaleneacetic acid (NAA) was loaded in the hydrogel by taking advantage of its hydrophobic interaction with the cavities of beta-CD. The releases of blue dextran (a water-soluble dye) from the hydrogels were promoted, as the pHs of the media increased. When the molar ratio of EPI to beta-CD was lower, the degrees of release were higher, and the pH dependency of the release became more prominent. In fact, the swelling ratio of the hydrogels having a lower molar ratio of EPI to beta-CD was higher. The higher swelling ratio would account for the higher degree of release and the marked pH sensitivity.

  4. Fluorometric and theoretical studies on inclusion complexes of β-cyclodextrin and D-, L-phenylalanine

    NASA Astrophysics Data System (ADS)

    Aree, Thammarat; Arunchai, Rungthiwa; Koonrugsa, Narongsak; Intasiri, Amarawan

    2012-10-01

    Inclusion complexes of β-cyclodextrin (β-CD) with L- and D-phenylalanine (Phe) have been characterized in solution by fluorometry and in gas phase by semiempirical PM3 calculations. The unimolar stoichiometric ratio of both β-CD-L-Phe and β-CD-D-Phe complexes and the stability constants (K) were deduced from fluorometric titrations. The β-CD-L-Phe complex is more stable than the β-CD-D-Phe complex as indicated by the larger K values, 21.1 vs. 6.86 M-1. This is consistent with the stabilization energies (ΔEstb) and inclusion geometries obtained from PM3 calculations. The β-CD-L-Phe complex with L-Phe residing in the central β-CD cavity and pointing its COOH group downwards to the O6 end has ΔEstb = -62.7 kJ mol-1, whereas the β-CD-D-Phe complex with D-Phe placing at 3 Å beneath the β-CD O4-plane and pointing its COOH group upwards to the O2/O3 end has ΔEstb = -53.3 kJ mol-1. The unison of host-guest intermolecular hydrogen bonds, hydrophobic interactions and molecular deformations plays an essential role in forming and stabilizing the inclusion complexes. Our results show that the β-CD-L-Phe and β-CD-D-Phe inclusion complexes are relatively stable and differentiable, suggesting the applications of CDs in foods and drugs.

  5. 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.

  6. Nimesulide/methyl β-cyclodextrin inclusion complexes: physicochemical characterization, solubility, dissolution, and biological studies.

    PubMed

    Auda, Sayed H

    2014-03-01

    Nimesulide (NIM) is an insoluble nonsteroidal anti-inflammatory drug (NSAID). Complexation of drug with methyl β-cyclodextrin was evaluated to improve solubility and dissolution rate of NIM. Complexation was achieved via a coevaporation technique to obtain different drug to polymer molar ratios (1:1, 1:2, and 1:3). The physicochemical characterization of the systems using powder X-ray diffraction and infrared spectroscopy was carried out to understand the influence of this technological process on the physical status of single components and complex systems and to detect possible interactions between drug and carrier. Moreover, quantitative solubility and in vitro dissolution studies of NIM alone and NIM inclusion complexes were studied in the dissolution media of phosphate buffer pH 5.5 and 7.4. The analysis provided existence of a molecular interaction between drug and carrier together in the complex state. The study showed that the inclusion systems enhanced of drug solubility, dissolution rate, and anti-inflammatory activity.

  7. Analytical characterization of a ferulic acid/gamma-cyclodextrin inclusion complex.

    PubMed

    Anselmi, Cecilia; Centini, Marisanna; Ricci, Maurizio; Buonocore, Anna; Granata, Paola; Tsuno, Takuo; Facino, Roberto Maffei

    2006-03-03

    Ferulic acid (FA) is a well-known antioxidant of natural source with promising properties as photoprotective agent (approved in Japan as sunscreen) and its derivatives (alkyl ferulates) are under screening for the prevention of photoinduced skin tumours. In the present work we describe the preparation of a solid inclusion complex between ferulic acid and gamma-cyclodextrin (gamma-CD) and its characterization by different analytical techniques: differential scanning calorimetry (DSC), X-ray diffractometry (XRD), nuclear magnetic resonance spectroscopy (1H NMR) and by supporting information of molecular modelling. All these approaches indicate that ferulic acid is able to form an association complex with gamma-CD but only 1H NMR and molecular modelling studies give an unequivocal evidence that the antioxidant molecule is embedded into the gamma-CD cavity to form an inclusion complex. In detail it is entrapped inside the hydrophobic core of gamma-CD with the lipophilic aromatic ring and the ethylenic moieties, leaving the more polar functional groups close to wider rim or outside the cavity.

  8. Effect of beta-cyclodextrin on pasting properties of wheat starch.

    PubMed

    Li, W D; Huang, J C; Corke, H

    2000-06-01

    Changes of viscosity characteristics of genetically diverse hexaploid wheat starches during pasting in water, 1% NaCl solution, or at pH 4 or pH 10 were studied using a Rapid Visco-Analyzer. Peak viscosity (PV), hot paste viscosity (HPV) and cool paste viscosity (CPV) of all the wheat starches was little affected in pH 4 and pH 10 treatments. In 1% NaCl, all starches showed substantial increases in all three parameters relative to pasting in water. The use of 1% beta-cyclodextrin (beta-CD) (cycloheptaamylose) solution increased PV of high-swelling starches, but generally slightly decreased that of low swelling starches in all treatment conditions. HPV was always reduced by addition of 1% beta-CD, but CPV was increased in most treatments for Anza and Yecora Rojo (low swelling), but decreased for Klasic (high swelling). Bacterial alpha-amylase was added to starch or flour. The effect of beta-CD was shown to be independent of alpha-amylase inhibition in wheat starch, but beta-CD strongly inhibited alpha-amylase in wheat flour.

  9. Crystal structure of a new cyclomaltoheptaose hydrate: beta-cyclodextrin.7.5H2O.

    PubMed

    Li, Jian-Ye; Sun, Dao-Feng; Hao, Ai-You; Sun, Hong-Yuan; Shen, Jian

    2010-03-30

    The crystallographic study of a partially hydrated form of cyclomaltoheptaose (beta-cyclodextrin, betaCD) is reported. C(42)H(70)O(35).7.5H(2)O; space group P2(1) with unit cell constants a=15.1667(5), b=10.1850(3), c=20.9694(7)A, beta=110.993(2) degrees ; final discrepancy index R=0.0760 for the 6181 observed reflections and 784 refined parameters. One water molecule is included in the cavity and distributed over two partially occupied positions, the other 6.5 waters distributed over eight positions are located as space-filler between the macrocycles. The crystal structure belongs to the cage-type, like that observed in Form I (betaCD.12H(2)O; Lindner, K; Saenger, W. Carbohydr. Res. 1982, 99, 103-115) and Form II (betaCD.11H(2)O; Betzel, C., et al. J. Am. Chem. Soc., 1984, 106, 7545-7567).

  10. Chromatographic and spectroscopic studies on the chiral recognition of sulfated beta-cyclodextrin as chiral mobile phase additive enantiomeric separation of a chiral amine.

    PubMed

    Ma, Shengli; Shen, Sherry; Haddad, Nizar; Tang, Wenjun; Wang, Jing; Lee, Heewon; Yee, Nathan; Senanayake, Chris; Grinberg, Nelu

    2009-02-20

    A fast enantiomeric separation of a chiral aromatic amine was achieved, using ultra high pressure liquid chromatography and highly sulfated beta-cyclodextrin (S-beta-CD) as a chiral additive in the mobile phase. The stationary phase consisted of a core-shell support with a particle size of 2.7mum. Under these conditions the base-line separation was obtained within 2.5min. The influence of the concentration of the additive, along with the thermodynamics of the separation, was studied. Vibrational circular dichroism (VCD) spectroscopy was applied to assess the absolute configuration of the two enantiomeric analytes, as well as the interaction of these enantiomers with the S-beta-CD. The VCD results revealed that S-beta-CD undergoes a temperature-induced conformational change. Further, VCD experiments indicate that the interactions of the two enantiomers with the S-beta-CD occur through an inclusion of the aromatic part of the analyte, as well as through electrostatic interaction between the protonated amine and the sulfate groups located at the narrow part of the S-beta-CD. Molecular mechanics calculations performed according to the VCD results are consistent with experimental data, providing further evidence of these interactions.

  11. 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.

  12. 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.

  13. 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.

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

    PubMed

    Srinivasan, K; Stalin, T; Sivakumar, K

    2012-08-01

    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 (pK(a)) of host-guest inclusion complex (2,4-DNP-β-CD) were studied. The binding constant of inclusion complex at 303K 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 (1)H NMR, FT-IR, XRD and SEM analysis. A schematic representation of this inclusion process is proposed by molecular docking studies using PatchDock server.

  15. Synthesis of beta-cyclodextrin-modified water-dispersible Ag-TiO2 core-shell nanoparticles and their photocatalytic activity.

    PubMed

    Shown, Indrajit; Ujihara, Masaki; Imae, Toyoko

    2011-04-01

    The beta-cyclodextrin-modified Ag-TiO2 core-shell nanoparticles were prepared by sodium borohydrate reduction of AgNO3 and the subsequent hydrolysis of the tetraisopropyl orthotitanate in an aqueous medium. Inversely in the preparation of beta-cyclodextrin-modified TiO2-Ag core-shell nanoparticles, first hydrolysis and then following reduction were carried out. The synthesized spherical core-shell nanoparticles were highly water-dispersible and had an average diameter in the range of 9 to 12 nm. A significant shifting of surface plasmon band was observed for the synthesized Ag-TiO2 and TiO2-Ag core-shell nanoparticles. On a model reaction, namely, the photodegradation of phenol by the UV light irradiation, the photocatalytic property of TiO2 nanoparticles was enhanced, when the Ag nanoparticle was embedded in the core of TiO2 nanoparticles but TiO2 nanoparticles coated by Ag shell decreased the photocatalytic property of TiO2 nanoparticles. The mechanism is ascribed to the surface plasmon characteristics of Ag in the core of the TiO2 nanoparticles under the acceleration by host-guest inclusion characteristics.

  16. Solid inclusion complexes of vanillin with cyclodextrins: their formation, characterization, and high-temperature stability.

    PubMed

    Kayaci, Fatma; Uyar, Tamer

    2011-11-09

    This study reports the formation of solid vanillin/cyclodextrin inclusion complexes (vanillin/CD ICs) with the aim to enhance the thermal stability and sustained release of vanillin by inclusion complexation. The solid vanillin/CD ICs with three types of CDs (α-CD, β-CD, and γ-CD) were prepared using the freeze-drying method; in addition, a coprecipitation method was also used in the case of γ-CD. The presence of vanillin in CD ICs was confirmed by FTIR and (1)H NMR studies. Moreover, (1)H NMR study elucidated that the complexation stoichiometry for both vanillin/β-CD IC and vanillin/γ-CD IC was a 1:1 molar ratio, whereas it was 0.625:1 for vanillin/α-CD IC. XRD studies have shown channel-type arrangement for CD molecules, and no diffraction peak for free vanillin was observed for vanillin/β-CD IC and vanillin/γ-CD IC, indicating that complete inclusion complexation was successfully achieved for these CD ICs. In the case of vanillin/α-CD IC, the sample was mostly amorphous and some uncomplexed vanillin was present, suggesting that α-CD was not very effective for complexation with vanillin compared to β-CD and γ-CD. Furthermore, DSC studies for vanillin/β-CD IC and vanillin/γ-CD IC have shown no melting point for vanillin, elucidating the true complex formation, whereas a melting point for vanillin was recorded for vanillin/α-CD IC, confirming the presence of some uncomplexed vanillin in this sample. TGA thermograms indicated that thermal evaporation/degradation of vanillin occurred over a much higher temperature range (150-300 °C) for vanillin/CD ICs samples when compared to pure vanillin (80-200 °C) or vanillin/CD physical mixtures, signifying that the thermal stability of vanillin was increased due to the inclusion complexation with CDs. Moreover, headspace GC-MS analyses indicated that the release of vanillin was sustained at higher temperatures in the case of vanillin/CD ICs due to the inclusion complexation when compared to vanillin

  17. [Solubilization Specificities Interferon beta-1b from Inclusion Bodies].

    PubMed

    Zhuravko, A S; Kononova, N V; Bobruskin, A I

    2015-01-01

    A new solubilization method of recombinant interferon beta-1b (IFNβ-1b) from the inclusion bodies was developed. This method allows to extract the target protein selectively in the solutions of different alcohols, such as ethanol, propanol and isopropanol. It was shown that the more effective IFNβ-1b solubilization was achieved in the 55% propanol solution. This method allowed to extract the target protein from inclusion bodies around 85-90%, and significantly reduced Escherichia coli content in the solubilizate, in comparison with standard methods.

  18. Carboxymethyl-beta-cyclodextrin mitigates toxicity of cadmium, cobalt, and copper during naphthalene biodegradation.

    PubMed

    Hoffman, Douglas R; Anderson, Phillip P; Schubert, Carissa M; Gault, Melissa B; Blanford, William J; Sandrin, Todd R

    2010-04-01

    Hazardous waste sites are commonly contaminated with both organic and metal pollutants. Many metal pollutants have been shown to inhibit organic pollutant biodegradation. We investigated the ability of a modified, polydentate cyclodextrin (carboxymethyl-beta-cyclodextrin, CMCD) to reduce the toxicity of 33.4 microM cadmium, cobalt or copper during naphthalene degradation by a Burkholderia sp. in 120 h aerobic, batch studies. The highest investigated concentration of CMCD, 3340 microM, reduced cadmium, cobalt, and copper toxicity. With each metal, the length of the lag phase was reduced (by as much as 108 h with cobalt or copper), the cell yield was increased (by as much as a factor of 16 with cobalt), and the growth rate was increased (by as much as a factor of 31 with cobalt). The degrader was unable to use CMCD as the sole source of carbon and energy. Our data suggest that the ability of CMCD to complex metals plays an important role in its ability to mitigate metal toxicity and that CMCD has the potential to enhance biodegradation in organic and metal co-contaminated environments.

  19. Utility of cyclodextrins in the formulation of genistein part 1. Preparation and physicochemical properties of genistein complexes with native cyclodextrins.

    PubMed

    Daruházi, Agnes Emma; Szente, Lajos; Balogh, Balázs; Mátyus, Péter; Béni, Szabolcs; Takács, Mária; Gergely, András; Horváth, Péter; Szoke, Eva; Lemberkovics, Eva

    2008-11-04

    Isoflavones are suitable guest molecules for inclusion complex formation with cyclodextrins (CDs). The molecular encapsulation with CDs results in a solid, molecularly dispersed form and in a significantly improved aqueous solubility of isoflavones. Genistein, a key isoflavone constituent of Ononidis spinosae radix was found to form a supramolecular, non-covalent inclusion complex with both beta-cyclodextrin (beta-CD) and gamma-cyclodextrin (gamma-CD), while it did not form a stable complex with alpha-CD. The guest genistein was found to spatially located in the less polar cavity of cyclodextrin. The isolated binary genistein/CD complexes appeared novel crystalline lattices. The in vitro dissolution of genistein entrapped into both beta- and gamma-CD, significantly surpassed that of the plain isoflavone.

  20. 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.

  1. Characterization, inclusion mode, phase-solubility and in vitro release studies of inclusion binary complexes with cyclodextrins and meglumine using sulfamerazine as model drug.

    PubMed

    Aloisio, Carolina; Gomes de Oliveira, Anselmo; Longhi, Marcela

    2014-07-01

    In order to investigate the effect on the aqueous solubility and release rate of sulfamerazine (SMR) as model drug, inclusion complexes with β-cyclodextrin (βCD), methyl-β-cyclodextrin (MβCD) and hydroxypropyl-β-cyclodextrin (HPβCD) and a binary system with meglumine (MEG) were developed. The formation of 1:1 inclusion complexes of SMR with the CDs and a SMR:MEG binary system in solution and in solid state was revealed by phase solubility studies (PSS), nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis and X-Ray diffractometry (XRD) studies. The CDs solubilization of SMR could be improved by ionization of the drug molecule through pH adjustments. The higher apparent stability constants of SMR:CDs complexes were obtained in pH 2.00, demonstrating that CDs present more affinity for the unionized drug. The best approach for SMR solubility enhancement results from the combination of MEG and pH adjustment, with a 34-fold increment and a Smax of 54.8 mg/ml. The permeability of the drug was reduced due to the presence of βCD, MβCD, HPβCD and MEG when used as solubilizers. The study then suggests interesting applications of CD or MEG complexes for modulating the release rate of SMR through semipermeable membranes.

  2. 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).

  3. 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.

  4. Fabrication of 2D nanosheet through self assembly behavior of sulfamethoxypyridazine inclusion complexes with α- and β-cyclodextrins.

    PubMed

    Rajendiran, N; Venkatesh, G; Mohandass, T

    2014-04-05

    A 2D nanosheet was fabricated through the supramolecular self assembly of sulfamethoxypyridazine (SMP) and β-cyclodextrin (β-CD) inclusion complexes. HRTEM image exhibited 2D nanosheet morphology with a length of 1200mm and the sheet thickness of 60mm. It is noted that the nanosheet did not form a single layer aggregation but a bulk aggregation of SMP/β-CD inclusion complex. The formation of this multilayer 2D nanosheet based on the self assembly of SMP/β-CD inclusion complexes is proposed by the topological transformation as well as molecular modeling calculations. But, nanorods are formed in SMP/α-CD inclusion complex indicated that the nature of the CD determined the shape of the self assembled supramolecular architecture. The formation of nanomaterial was characterized by using FT-IR, DSC, PXRD, (1)H NMR, absorption, fluorescence and lifetime measurements.

  5. Preparation, characterization, and in vitro anti-inflammatory evaluation of novel water soluble kamebakaurin/hydroxypropyl-β-cyclodextrin inclusion complex

    NASA Astrophysics Data System (ADS)

    Raza, Aun; Sun, Huifang; Bano, Shumaila; Zhao, Yingying; Xu, Xiuquan; Tang, Jian

    2017-02-01

    To enhance the aqueous solubility of kamebakaurin (KA), it was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, the interaction KA with HP-β-CD and their inclusion complex behavior were determined by different characterization techniques such as UV-vis, 1H NMR, FT-IR, PXRD and SEM. All the characterization information proved the development of inclusion complex KA/HP-β-CD, and this inclusion complex demonstrated discriminable spectroscopic characteristics and properties from free compound KA. The results demonstrated that the water solubility of KA was remarkably increased in the presence of HP-β-CD. Furthermore, in vitro anti-inflammatory study showed that inclusion complex KA/HP-β-CD maintained the anti-inflammatory effect of KA. These results demonstrate that HP-β-CD will be promisingly employed in the application of water-insoluble anti-inflammatory phytochemicals such as KA.

  6. Inclusion of lycorine with natural cyclodextrins (α-, β- and γ-CD): Experimental and in vitro evaluation

    NASA Astrophysics Data System (ADS)

    Liu, Dan-Dan; Guo, Ya-Fei; Zhang, Jian-Qiang; Yang, Zhi-Kuan; Li, Xiang; Yang, Bo; Yang, Rui

    2017-02-01

    The primary goal of this research was to investigate the effect of spatial compatibility in the inclusion complex formation of cyclodextrins with different cavity size on physicochemical and anticancer properties. For this purpose, the binding behaviors of the complex formations of α-, β- and γ-cyclodextrins with lycorine were observed by the use of UV, MS, XRD, DSC, TG, 1H, and 2D NMR spectroscopy and elemental analysis. The results displayed that the binding behavior was contrary to the size of the CDs, and the value of binding constant of lycorine/γ-CD was the smallest, while the value of binding constant of lycorine/α-CD was the greatest. In vitro study demonstrated that the lycorine-α-CD and lycorine-β-CD are valuable approaches to enhance lycorine bioavailability. The results deduced that using CDs with moderate cavities (such as α-CD or β-CD) as a cyclodextrin-based delivery system to form the lycorine-type inclusion complex could be more applicable, and further helps to improve the properties of lycorine-type therapeutic agent.

  7. 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.

  8. Supramolecular photochemistry in beta-cyclodextrin hosts: a TREPR, NMR, and CIDNP investigation.

    PubMed

    Krumkacheva, Olesya A; Gorelik, Vitaly R; Bagryanskaya, Elena G; Lebedeva, Natalia V; Forbes, Malcolm D E

    2010-06-01

    A systematic investigation of the photochemistry and ensuing radical chemistry of three guest ketones encapsulated in randomly methylated beta-cyclodextrin (beta-CD) hosts is reported. Dibenzyl ketone (DBK), deoxybenzoin (DOB), and benzophenone (BP) triplet states are rapidly formed after photolysis at 308 nm. Time-resolved electron paramagnetic resonance (TREPR) spectroscopy, steady-state NMR spectroscopy, and time-resolved chemically induced nuclear polarization (TR-CIDNP) experiments were performed on the ketone/CD complexes and on the ketones in free solution for comparison. The major reactivity pathways available from these excited states are either Norrish I alpha-cleavage or H-atom abstraction from the interior of the CD capsule or the solvent. The DOB triplet state undergoes both reactions, whereas the DBK triplet shows exclusively alpha-cleavage and the BP triplet shows exclusively H-atom abstraction. Radical pairs are observed in beta-CDs by TREPR, consisting of either DOB or BP ketyl radicals with sugar radicals from the CD interior. The TREPR spectra acquired in CDs are substantially broadened due to strong spin exchange. The electron spin polarization mechanism is mostly due to S-T(0) radical pair mechanism (RPM) in solution but changes to S-T(-) RPM in the CDs due to the large exchange interaction. The TR-CIDNP results confirm the reactivity patterns of all three ketones, and DOB shows strong nuclear spin polarization from a novel rearrangement product resulting from the alpha-cleavage reaction.

  9. 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

  10. Synthesis, characterization and in vitro release studies of a new acetazolamide-HP-beta-CD-TEA inclusion complex.

    PubMed

    Granero, Gladys E; Maitre, Marcos M; Garnero, Claudia; Longhi, Marcela R

    2008-03-01

    The aim of our work was to develop a multicomponent inclusion complex of acetazolamide (ACZ) in order to investigate the combined effect of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and triethanolamine (TEA) on the solubility of ACZ and its possibility of ophthalmic delivery. Phase solubility study was used to evaluate the complexation in solution at 25 degrees C. Complex formation was also evaluated by comparing the infrared (FT-IR) spectra of the solid complexes with a simple physical mixture containing the same amount of ACZ. FT-IR experiments provided data indicating that the carbonamido group of ACZ is involved in the inclusion process. In vitro release data showed that both formulations, containing the freeze-dried ternary complex and the corresponding simple physical mixture of ACZ with HP-beta-CD and TEA presented the fastest release rate of ACZ. These results suggest that the ACZ-HP-beta-CD-TEA complex represents an effective novel formulation to enhance ACZ solubility in water, turning it promising for ophthalmic administration.

  11. 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.

  12. Experimental and theoretical study of the inclusion complexes of 3-carboxycoumarin acid with β- and 2-hydroxypropyl-β-cyclodextrins

    NASA Astrophysics Data System (ADS)

    Tablet, Cristina; Minea, Liliana; Dumitrache, Luigi; Hillebrand, Mihaela

    2012-06-01

    The association process of a host-guest system, cyclodextrins (CyD) - 3-carboxycoumarin acid (3CCA) was followed by means of UV-vis, circular dichroism and steady-state fluorescence spectroscopies in buffer solution at pH = 1. The experimental data were analyzed in order to get information on the stoichiometry, the equilibrium constants and the geometry of the inclusion complexes. In the circular dichroism spectra, a positive induced signal was obtained reflecting that the guest penetrates the cavity in such a way that the transition moment of the electronic band is quasi parallel to the host main axis. The experimental data are supported by the DFT and TDDFT (B3LYP/6-31G) calculations performed on the isolated ligand and by TDDFT (ZINDO) calculations carried out on the supramolecular ligand-cyclodextrin system.

  13. 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

  14. 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.

  15. 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

    2001-05-08

    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.

  16. 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

  17. Removal of copper ions from water using epichlorohydrin cross-linked beta-cyclodextrin polymer: characterization, isotherms and kinetics.

    PubMed

    Sikder, M Tajuddin; Islam, Md Shariful; Kikuchi, Tohru; Suzuki, Junichi; Saito, Takeshi; Kurasaki, Masaaki

    2014-04-01

    Beta-cyclodextrin (beta-CD) cross-linked with epichlorohydrin to form water insoluble beta-cyclodextrin polymer (beta-CDP) has been shown to be an effective sorbent for sorption of organic particles, but the sorption of copper (Cu2+) in aqueous solutions by beta-CDP has not been conducted. The objective of this study was to explore the sorption mechanism of beta-CDP for copper. The effects of different experimental conditions such as pH, ionic strength, contact time, and temperature were inspected using a batch method. In addition, binding scheme was estimated by using Fourier transform infrared (FTIR) spectroscopy, Xray photoelectron spectroscopy (XPS), a scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET) analysis. The adsorption of Cu2+ was observed to be higher at pH 6.0. The kinetic study revealed that the adsorption is fitted well by the pseudo-second-order kinetic model. The maximum binding of Cu2+ was estimated to be 111.11 mg/g through the Langmuir isotherm model--much higher than the existing sorption technologies. Hence, the adsorption-desorption trends of epichlorohydrin cross-linked with beta-CD, along with its good recyclability, establish an alternative, effective, and novel remediation technology for the removal of Cu2+ from aqueous solutions.

  18. Excimer formation in inclusion complexes of β-cyclodextrin with salbutamol, sotalol and atenolol: Spectral and molecular modeling studies

    NASA Astrophysics Data System (ADS)

    Antony Muthu Prabhu, A.; Subramanian, V. K.; Rajendiran, N.

    2012-10-01

    The inclusion complexation behavior of salbutamol, sotalol and atenolol drugs with β-cyclodextrin (β-CD) were investigated by UV-visible, fluorometry, time resolved fluorescence, FT-IR, 1H NMR, SEM and PM3 methods. The above drugs gave a single emission maximum in water where as dual emission in β-CD. In β-CD solutions the shorter wavelength fluorescence intensity was regularly decreased and longer wavelength fluorescence intensity increased. Addition of β-CD to aqueous solutions of drugs resulted into excimer emission. The excimer emission is concluded to be due to a 1:2 inclusion complex between β-CD and drug. Nanosecond time-resolved studies indicated that all drugs exhibited biexponential decay in solvents and triexponential decay in CD. Investigations of thermodynamic and electronic properties confirmed the stability of the inclusion complex.

  19. 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.

  20. Methyl-beta-cyclodextrin directly binds methylene blue and blocks both its cell staining and glucose uptake stimulatory effects.

    PubMed

    Scott, Jordan; Tidball, Andrew; Uitvlugt, Jeff M; Lucia, Mario; Vander Griend, Douglas A; Louters, Larry L

    2009-02-01

    GLUT1, the most ubiquitously expressed member of the GLUT family of glucose transporters, can be acutely activated by a variety of cell stresses. Methylene blue activates glucose transport activity of GLUT1 in L929 fibroblast cells presumably by a redox cycling of MB, which generates an oxidative stress. Data shown here reveal that methyl-beta-cyclodextrin (MCD) blocks both the staining of cells and activation of glucose uptake by directly binding to MB. MCD binding to MB was qualitatively demonstrated by a significantly slower dialysis rate of MB in the presence of MCD. Analysis of the complete spectra of aqueous MB solutions and MB plus MCD solutions by a factor analysis program called SIVVU indicated that these equilibria can be modeled by three species: MB monomer, MB dimer, and MCD-MB inclusion complex. The molar extinction coefficients for each species from 500 to 700nm were determined. The equilibrium association constant (K(a)) for MB dimer formation was measured at 5846+/-30M(-1) and the K(a) for formation of the MCD-MB complex was 310+/-10M(-1). MCD also dramatically enhances the destaining rate of MB-stained cells. The loss of MB from the cell is tightly correlated with the loss of activated glucose uptake. This suggests that the MB activation of glucose uptake is likely not caused by its redox cycling, but more likely the result of a specific interaction between MB and a protein directly involved in the activation of GLUT1.

  1. Synthesis and structure-activity study of quaternary ammonium functionalized beta-cyclodextrin-carboxymethylcellulose polymers.

    PubMed

    Bonenfant, Danielle; Bourgeois, François-René; Mimeault, Murielle; Monette, Frédéric; Niquette, Patrick; Hausler, Robert

    2011-01-01

    Carboxymethylcellulose (CMC) and beta-cyclodextrin (beta-CD)-based polymers functionalized with two types of quaternary ammonium compounds (QACs), the alkaquat DMB-451 (N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride) (DMD-451) named polymer DMB-451, and FMB 1210-8 (a blend of 32 w% N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride and 48 w% of didecyldimethylammonium chloride) named polymer FMB 1210-8, were synthethized and characterized by Fourier transform infrared spectroscopy. The antimicrobial activities of these polymers against Eschericia coli were also evaluated at 25 degrees C in wastewater. The results have indicated that the polymer FMB 1210-8 possesses a high-affinity binding with bacterial cells that induces a rapid disinfection process. Moreover, in the same experimental conditions of disinfection (mixture of 1.0 g of polymer and 100 mL of wastewater), the polymer FMB 1210-8 has a higher antimicrobial efficiency (99.90%) than polymer DMB-451 (92.8%). This phenomenon might be associated to a stronger interaction with bacterial cells due to stronger binding affinity for E. coli cells and greater killing efficiency of the C10 alkyl chains QAC of polymer FMB 1210-8 to disrupt the bacterial cell membrane as compared to N-alkyl (50% C14, 40% C12, 10% C10) dimethylbenzylammonium chloride. Together, these results suggest that the polymer FMB 1210-8 could constitute a good disinfectant against Escherichia coli, which could be advantageously used in wastewater treatments due to the low toxicity of beta-CD and CMC, and moderated toxicity of FMB 1210-8 to human and environment.

  2. A highly hydrated α-cyclodextrin/1-undecanol inclusion complex: crystal structure and hydrogen-bond network from high-resolution neutron diffraction at 20 K.

    PubMed

    Gallois-Montbrun, Delphine; Le Bas, Geneviève; Mason, Sax A; Prangé, Thierry; Lesieur, Sylviane

    2013-04-01

    The monoclinic C2 crystal structure of an α-cyclodextrin/1-undecanol host-guest inclusion complex was solved using single-crystal neutron diffraction. Large high-quality crystals were specially produced by optimizing temperature-controlled growth conditions. The hydrate crystallizes in a channel-type structure formed by head-to-head dimer units of α-cyclodextrin molecules stacked like coins in a roll. The alkyl chain of the guest lipid is entirely embedded inside the tubular cavity delimited by the α-cyclodextrin dimer and adopts an all-trans planar zigzag conformation, while the alcohol polar head group is outside close to the α-cyclodextrin primary hydroxyl groups. The cyclodextrin dimer forms columns, which adopt a quasi-square arrangement much less compact than the quasi-hexagonal close packing already observed in the less hydrated α-cyclodextrin channel-type structures usually found with similar linear guests. The lack of compactness of this crystal form is related to the high number of interstitial water molecules. The replacement of 1-undecanol by 1-decanol does not modify the overall crystal structure of the hydrate as shown by additional X-ray diffraction investigations comparing the two host-guest assemblies. This is the first study that analyses the entire hydrogen-bonding network involved in the formation of a cyclodextrin dimer surrounded by its shell of water molecules.

  3. Solvent and guest isotope effects on complexation thermodynamics of alpha-, beta-, and 6-amino-6-deoxy-beta-cyclodextrins.

    PubMed

    Rekharsky, Mikhail V; Inoue, Yoshihisa

    2002-10-16

    The stability constant (K), standard free energy (DeltaG degrees ), enthalpy (DeltaH degrees ), and entropy changes (TDeltaS degrees ) for the complexation of native alpha- and beta-cyclodextrins (CDs) and 6-amino-6-deoxy-beta-CD with more than 30 neutral, positively, and negatively charged guests, including seven fully or partially deuterated guests, have been determined in phosphate buffer solutions (pH/pD 6.9) of hydrogen oxide (H(2)O) or deuterium oxide (D(2)O) at 298.15 K by titration microcalorimetry. Upon complexation with these native and modified CDs, both nondeuterated and deuterated guests examined consistently exhibited higher affinities (by 5-20%) in D(2)O than in H(2)O. The quantitative affinity enhancement in D(2)O versus H(2)O directly correlates with the size and strength of the hydration shell around the charged/hydrophilic group of the guest. For that reason, negatively/positively charged guests, possessing a relatively large and strong hydration shell, afford smaller K(H2O)/K(D2O) ratios than those for neutral guests with a smaller and weaker hydration shell. Deuterated guests showed lower affinities (by 5-15%) than the relevant nondeuterated guests in both H(2)O and D(2)O, which is most likely ascribed to the lower ability of the C-D bond to produce induced dipoles and thus the reduced intracavity van der Waals interactions. The excellent enthalpy-entropy correlation obtained can be taken as evidence for the very limited conformational changes upon transfer of CD complexes from H(2)O to D(2)O.

  4. 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.

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

    PubMed

    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=80-11700 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.

  6. 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

  7. Amorphous solid dispersion studies of camptothecin-cyclodextrin inclusion complexes in PEG 6000.

    PubMed

    Fatmi, Sofiane; Bournine, Lamine; Iguer-Ouada, Mokrane; Lahiani-Skiba, Malika; Bouchal, Fatiha; Skiba, Mohamed

    2015-01-01

    Abstract: The present work focused on the solubility enhancement of the poorly water-soluble anti-cancer agent camptothecin which, in its natural state, presents poor solubility inducing lack of activity with a marked toxicity. A new approach is adopted by using a ternary system including camptothecin (CPT) and cyclodextrins (CDs) dispersed in polyethylene glycol (PEG) 6000. Camptothecin solubility variations in the presence of α-CD, β-CD, γ-CD, hydroxypropyl-α-CD (HPα-CD), hydroxypropyl-β-CD (HPβ-CD), permethyl-β-CD (PMβ-CD) and sulfobutyl ether-β-CD (SBEβ-CD), were evaluated by Higuchi solubility experiments. In the second part, the most efficient camptothecin/P-CDs binary systems, mainly HPβ-CD and PMβ-CD, were dispersed in PEG 6000. In addition to a drug release and modeling evaluation, the CPT interactions with CDs and PEG 6000 to prepared the amorphous solid dispersion in the binary and ternary systems were investigated by Fourier transformed infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analyses (TGA) and X-ray powder diffraction (XRPD). The results showed that HPβ-CD and PMβ-CD were the most efficient for camptothecin solubilization with highest apparent equilibrium constants. Dissolution studies showed that percentage of CPT alone after two hour in 0.1 M HCI medium, did not exceed 16%, whereas under the same conditions, CPT/PMβ-CD complex reached 76%. When dispersing the binary systems CPT/β-CDs in PEG 6000, the velocity and the percentage of CPT release were considerably improved whatever the CD used, reaching the same value of 85%. The binary and ternary systems characterization demonstrated that CPT inclused into the CDs cavity, replacing the water molecules. Furthermore, a drug transition from crystalline to amorphous form was obtained when solid dispersion is realized. The present work demonstrated that ternary complexes are promising systems for CPT encapsulation, and offer opportunities to

  8. Recovery and purification of cholesterol from cholesterol-β-cyclodextrin inclusion complex using ultrasound-assisted extraction.

    PubMed

    Li, Yong; Chen, Youliang; Li, Hua

    2017-01-01

    Response surface methodology was used to optimize ultrasound-assisted ethanol extraction (UAE) of cholesterol from cholesterol-β-cyclodextrin (C-β-CD) inclusion complex prepared from duck yolk oil. The best extraction conditions were solvent-solid ratio 10mL/g, ultrasonic power 251W, extraction temperature 56°C and sonication time 36min. Under these conditions, the highest cholesterol extraction yield and cholesterol content obtained 98.12±0.25% and 43.38±0.61mg/g inclusion complex, respectively. As compared with Reflux extraction and Soxhlet extraction, the UAE was more efficient and economical. To increase the purity of crude cholesterol extraction, silica gel column chromatography and crystallization were carried out. Finally, cholesterol was obtained at 95.1% purity, 71.7% recovery and 22.0% yield.

  9. Insight into the structural deformations of beta-cyclodextrin caused by alcohol cosolvents and guest molecules.

    PubMed

    Zhang, Haiyang; Ge, Chunling; van der Spoel, David; Feng, Wei; Tan, Tianwei

    2012-03-29

    Beta-cyclodextrin (β-CD) is an ideal candidate for a host molecule, and it is used as such in drug delivery and separation technology. The structural behavior of free β-CD and host-guest complexes of β-CD with two isoflavonoid isomers (puerarin and daidzin) in aqueous alcohol solutions, covering methanol, ethanol, 2-propanol, and 1-propanol, was investigated through molecular dynamics (MD) simulations. The MD results highlighted aspects of the structural flexibility and rigidity of β-CD in different alcohol solutions. The alcohol residence time within the β-CD cavity, solvent distribution around β-CD, and guest-induced structural changes were analyzed. Interaction with puerarin endowed β-CD with a more rigid structure than with daidzin and a weaker ternary complex β-CD/puerarin/alcohol was formed with a local participation of water molecules. The retention behavior of puerarin and daidzin on a β-CD-coupled medium was determined via chromatographic experiments and simulation results provided a structural explanation for such interactions.

  10. 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

  11. Determining conditional stability constants for Pb complexation by carboxymethyl-beta-cyclodextrin (CMCD).

    PubMed

    Skold, Magnus E; Thyne, Geoffrey D; Drexler, John W; McCray, John E

    2007-08-15

    Carboxymethyl-beta-cyclodextrin (CMCD) has been proposed for remediation of metal-contaminated sediments. This research presents stability constants for CMCD-lead complexes, and demonstrates a rigorous methodology for estimating stability constants for metal-complexing agents. The conditional stability constant for the lead-CMCD aqueous complex was determined to be 10(5.18) with the 95% confidence interval ranging from 10(5.14) to 10(5.22). The best fit for experimental data was made by assuming a reaction between divalent CMCD(2-) and Pb(2+) and using the WATEQ activity coefficient formulation. The optimized value was derived from experimental data with the geochemical model PHREEQC coupled to UCODE_2005, a parameter optimization program. Like FITEQL, UCODE has a built-in option to optimize parameter values by minimizing the weighted sum of squared residuals (WSSR). However, our approach not only allows rapid, automatic optimization of the stability constant, but also allows determination of uncertainties in estimated parameter values and statistical analysis to assess the appropriateness of the conceptual model. The automation of the process allows testing of multiple conceptual models and the final values produced are internally consistent with the PHREEQC database. In this case five different conceptual models to describe the metal complexation and protonation reactions of CMCD were considered.

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

    PubMed

    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

    2014-04-08

    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.

  13. Crystallographic evidence for β-cyclodextrin inclusion complexation facilitating the improvement of antioxidant activity of tea (+)-catechin and (-)-epicatechin.

    PubMed

    Aree, Thammarat; Jongrungruangchok, Suchada

    2016-04-20

    Single-crystal X-ray analysis to 0.6Å resolution using synchrotron radiation of the inclusion complexes of β-cyclodextrin (β-CD) with (+)-catechin (CA) and (-)-epicatechin (EC) has been carried out to gain atomistic insight into how the inclusion complexation helps to improve tea catechin antioxidant activity. The β-CD-CA complex crystallizes in the monoclinic P21 space group, whereas the β-CD-EC complex crystallizes in both the monoclinic P21 and triclinic P1 space groups. In comparing the inclusion structures, the β-CD-EC dimeric structure having higher numbers of OH⋯O hydrogen bonds combined with π⋯π interactions is associated with its greater interaction energy, as derived from DFT/B3LYP single-point energy calculations. Detailed structural analysis of the CA, EC conformation and inclusion geometry reveals that the interplay of the intermolecular OH⋯O hydrogen bond stabilized catechol moiety and the protection of OH groups in the β-CD cavity plays a key role in the improvement of antioxidant capacity upon inclusion complexation.

  14. Inclusion complex of ITH12674 with 2-hydroxypropyl-β-cyclodextrin: Preparation, physical characterization and pharmacological effect.

    PubMed

    Michalska, Patrycja; Wojnicz, Aneta; Ruiz-Nuño, Ana; Abril, Sheila; Buendia, Izaskun; León, Rafael

    2017-02-10

    ITH12674 is a multitarget drug, designed to exert a dual "drug-prodrug" mechanism of action, able to induce the phase II antioxidant and anti-inflammatory response for the treatment of brain ischemia. However, its physicochemical properties limit its potential preclinical development due to its low water solubility and instability towards heat and pH variations. In order to improve its properties, we prepared the inclusion complex of ITH12674 with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) by the freeze-drying method. The formation of the inclusion complex was confirmed by FT-IR spectroscopy, PXRD, DSC, (1)H NMR and SEM techniques. Experimental results showed that the inclusion complex enhanced its water solubility and stability against heat, acidic and basic conditions. Furthermore, the inclusion complex, prepared in water solution, exerted the same potency to induce the phase II antioxidant response as the pure ITH12674. Thus the formation of the inclusion complex with HP-β-CD is a very effective method to stabilize and solubilize the active compound for its future preclinical development.

  15. 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.

  16. Downregulation of the p75 neurotrophin receptor in tissue culture and in vivo, using beta-cyclodextrin-adamantane-oligonucleotide conjugates.

    PubMed

    Epa, W R; Greferath, U; Shafton, A; Rong, P; Delbridge, L M; Bennie, A; Barrett, G L

    2000-12-01

    Formation of complexes with beta-cyclodextrin derivatives via adamantyl groups was found to enhance the uptake and antisense efficacy of phosphorothioate oligos targeted to the p75 neurotrophin receptor in neuronally differentiated PC12 cells. After a 2-week course of systemic administration to mice (by intraperitoneal injection), there was evidence of a pronounced uptake of these oligos by the dorsal root ganglia (DRG), as well as by liver and kidney. There was no uptake by the brain. Consistent with uptake of antisense oligos by the DRG, systemic administration resulted in marked and consistent downregulation of p75 in DRG neurons. These results indicate that cyclodextrin-adamantane-oligo conjugates have great potential as agents to downregulate target genes in neurons, particularly in vivo in the peripheral nervous system.

  17. Preparation of inclusion complex of apigenin-hydroxypropyl-β-cyclodextrin by using supercritical antisolvent process for dissolution and bioavailability enhancement.

    PubMed

    Huang, Yannian; Zu, Yuangang; Zhao, Xiuhua; Wu, Mingfang; Feng, Ziqi; Deng, Yiping; Zu, Chang; Wang, Lingling

    2016-09-25

    In this study, an inclusion complex of apigenin (AP)-hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared via supercritical antisolvent (SAS) method using N, N-dimethylformamide (DMF) as solvent and carbon dioxide as antisolvent. The mole ratio of AP and HP-β-CD (1:1) was established by phase solubility equilibrium experiment. The optimal conditions were determined through single-factor experiments; these conditions included precipitation pressure of 22.5MPa, precipitation temperature of 50°C, and AP concentration of 20mg/ml. The load efficiency and encapsulation efficiency of the AP-HP-β-CD inclusion complex, with a mean particle size of 392.13±7.56nm, were 13.97%±0.17% and 93.22%±1.17%, respectively, under the optimal conditions. FTIR, (1)H NMR, SEM, XRD, DSC, and TG analyses were also conducted. Results showed that the inclusion complex was formed because of the interaction between AP and HP-β-CD. DMF residue in the inclusion complex was 0.033% lower than the ICH limit for class II solvents. The solubility of the inclusion complex was approximately 152.43 times higher than that of the raw AP. In the in vitro study, the dissolution rate of the AP-HP-β-CD inclusion complex was about 7.60 times higher than that of the raw AP. In the in vivo study, the bioavailability of the inclusion complex increased by 6.45 times compared with that of the raw AP. Hence, the prepared AP-HP-β-CD inclusion complex exhibits potential as a new oral therapeutic agent formulation for clinical applications.

  18. Spontaneous association of hydrophobized dextran and poly-beta-cyclodextrin into nanoassemblies. Formation and interaction with a hydrophobic drug.

    PubMed

    Daoud-Mahammed, S; Ringard-Lefebvre, C; Razzouq, N; Rosilio, V; Gillet, B; Couvreur, P; Amiel, C; Gref, R

    2007-03-01

    New nanoassemblies were instantaneously prepared by mixing two aqueous solutions, one containing a beta-cyclodextrin polymer (pbetaCD), and the other a hydrophobically modified by alkyl chains dextran (MD). The formation mechanism and the inner structure of these nanoassemblies were analysed using surface tension measurements and (1)H NMR spectroscopy. The effect of a hydrophobic guest molecule, such as benzophenone (BZ), on the formation and stability of the nanoassemblies was also evaluated. MD exhibited the typical behaviour of a soluble amphiphilic molecule and adsorbed at the air/water interface. Whereas the injection of native beta-CDs in the solution beneath the adsorbed MD monolayer did not produce any change in the surface tension, that of the pbetaCD resulted in an increase in the surface tension, indicating the desorption of the polymer from the interface. This result accounts for a cooperative effect of beta-CDs linked together in the pbetaCD polymer on dextran desorption. The presence of benzophenone in the system hindered the sequestration of dextran alkyl moieties by beta-CD in the polymer without impeding the formation of associative nanoassemblies of 100-200 nm. (1)H NMR investigations demonstrated that, in the BZ-loaded nanoassemblies, the hydrophobic molecule was mainly located into the cyclodextrin cavities.

  19. Facile fabrication of narrowly-distributed polymeric micelles via host-guest inclusion complexation of hyperbranched polymers and cyclodextrin and its two-dimensional self-assembly.

    PubMed

    Sun, Xiaoyi; Huang, Wei; Zhou, Yongfeng; Yan, Deyue

    2010-10-14

    A novel narrowly-distributed (ND) polymeric micelle obtained in combination with host-guest recognition and self-assembly is reported. First, the adamantyl-terminated hyperbranched poly[3-ethyl-3-(hydroxymethyl)oxetane] (HBPO-AD) was synthesized by esterification of hyperbranched poly[3-ethyl-3-(hydroxymethyl)oxetane] (HBPO) with 1-adamantanecarbonyl chloride. Then the ND polymeric core-shell micelles, with the hydrophobic HBPO-AD cores and hydrophilic beta-cyclodextrin (β-CD) shells, were prepared via host-guest inclusion complexation of HBPO-AD and β-CD. The resultant polymer micelles were well characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Interestingly, after annealing at a temperature above the glass transition temperature (T(g)) for a certain time, the polymeric micelles can further self-assemble and fuse into two-dimensional (2D) sheets. The TEM, SEM and atomic force microscopy (AFM) characterization validate that the sheets are formed through stacking and fusion of tightly packed nanoparticles. In addition, the formation mechanism of polymeric complex micelles and 2D sheets has also been discussed.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Thermostable beta-cyclodextrin conjugates of two similar plant amine oxidases and their properties.

    PubMed

    Sebela, Marek; Kopecný, David; Lamplot, Zbynek; Havlis, Jan; Thomas, Henrik; Shevchenko, Andrej

    2005-02-01

    Syntheses of conjugates of garden pea (Pisum sativum) and grass pea (Lathyrus sativus) amine oxidases (PSAO and GPAO respectively) with BCD (beta-cyclodextrin), performed to improve the thermostability of the enzymes, are described in the present study. Periodate-oxidized BCD reacted with the enzyme proteins via free primary amino groups in a buffered solution containing cyanoborohydride as a reductant. Although the specific activities of PSAO and GPAO partially decreased after modification, Km values determined for the best diamine substrates remained almost unchanged. Both the BCD conjugates could be incubated at 65 degrees C for 30 min without considerable inactivation, and the residual activity remained detectable even after incubation at 75 degrees C. The conjugates contained approx. 30% of neutral sugars. Molecular masses of BCD-PSAO and BCD-GPAO (180 kDa), as estimated by gel-permeation chromatography, were higher compared with the value of 145 kDa for the native enzymes. This was in good correlation with the number of modified lysine residues determined by a spectrophotometric method. Peptide mass fingerprints of tryptic digests of BCD-PSAO and BCD-GPAO were less specific than those of the native enzymes when compared with the database sequence of PSAO. As a consequence of the modification, many unidentified peaks were observed in the digests of the studied conjugates that were not seen in the digests of native PSAO and GPAO. Only some of these peaks overlapped between BCD-PSAO and BCD-GPAO. The BCD conjugates described in the present study represent suitable candidates for biotechnological applications, e.g. in analyses using biosensors, which might benefit from increased storage stability and amine oxidation at high temperatures.

  5. Complexation of phosphine ligands with peracetylated beta-cyclodextrin in supercritical carbon dioxide: spectroscopic determination of equilibrium constants.

    PubMed

    Galia, Alessandro; Navarre, Edward C; Scialdone, Onofrio; Ferreira, Michel; Filardo, Giuseppe; Tilloy, Sebastien; Monflier, Eric

    2007-03-15

    The interaction between peracetylated beta-cyclodextrin and several triphenyl phosphine derivatives was studied in supercritical carbon dioxide (scCO2) by UV-visible spectroscopy. The equilibrium constant for a 1:1 complexation reaction was obtained from titration spectra and calculated using two established mathematical models. The values of the equilibrium constants are 1-3 orders of magnitude smaller than those obtained in aqueous solution with analogous phosphines. This is likely due to the absence in scCO2 of the hydrophobic effect, which is replaced by a corresponding, but weaker, CO2-phobic effect. The largest value of Kf was found for complexes of diphenyl(4-adamantylphenyl)phosphine, which is rationalized on the basis of the excellent fit of the phosphine in the cyclodextrin cavity, leading to enhanced host-guest van der Waals interactions. This study can be considered the first step toward the comprehension of the complexation thermodynamics of modified cyclodextrins soluble in scCO2.

  6. Electrocatalysis of chloroacetic acids (mono-, di- and tri-) at a C60-[dimethyl-(beta-cyclodextrin)]2 and nafion chemically modified electrode.

    PubMed

    Wei, M; Li, M; Li, N; Gu, Z; Zhou, X

    2001-01-26

    The C(60)-[dimethyl-(beta-cyclodextrin)](2) and nafion chemically modified electrode (CME) exhibits one electroreduction peak and two electro-oxidation peaks in a mixed solvent of water and acetonitrile (3:2, v/v) containing tetra-butylammonium perchlorate. The reduction of chloroacetic acids (mono-, di- and tri-) can be electrocatalyzed at this electrode, indicating that C(60)-[dimethyl-(beta-cyclodextrin)](2) is capable of mediating the electron transfer to chloroacetic acids. Values of the apparent catalytic rate constant, k, were determined by using the rotating-disk electrode (RDE).

  7. Study on inclusion complexation between plant growth regulator 6-benzylaminopurine and β-cyclodextrin: Preparation, characterization and molecular modeling

    NASA Astrophysics Data System (ADS)

    Ge, Xia; He, Jiang; Yang, Ying; Qi, Fengming; Huang, Zheng; Lu, Ruihua; Huang, Lizhen; Yao, Xiaojun

    2011-05-01

    An inclusion complex between the plant growth regulator 6-benzylaminopurine (6-BA) and β-cyclodextrin (β-CD) was prepared. A 1:1 host-guest stoichiometry was conformed by elemental analysis and Job's plot. From phase solubility diagram, a calculated apparent stability constant was 259.49 L/mol. The obtained complex was found to significantly improve the water solubility of 6-BA, and there was a 4.1-fold increase in the presence of 12 mmol/L β-CD as compared with the free 6-BA. Thermoanalysis, NMR and IR spectra were applied to characterize the complex. 1H NMR and ROESY results indicated that the benzene ring of 6-BA was included into the β-CD cavity, which was in agreement with the most predominant configuration optimized by molecular modeling.

  8. 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.

  9. 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.

  10. Combined effect of pH and polysorbates with cyclodextrins on solubilization of naringenin.

    PubMed

    Tommasini, S; Calabrò, M L; Raneri, D; Ficarra, P; Ficarra, R

    2004-10-29

    pH control and inclusion complex formation are commonly used as solubilization techniques in formulating ionizable drugs. Naringenin is a weakly acid compound with a low water solubility. The role of both ionized and unionized species of naringenin in solution by complexation with beta-cyclodextrin, 2-hydroxypropyl-beta-cyclodextrin and methyl-beta-cyclodextrin was investigated. This combined use of ionization and complexation increases not only the solubility of the unionized naringenin, but also that of the ionized one. This study puts on evidence the role of pH, pKa and complexation constants in increasing drug total aqueous solubility, determined by the single components in solution, as ionized and unionized naringenin both in free and complexed forms. Moreover, the presence of non-ionic surfactants in the media of complexation gives a positive contribution to the improvement of the solubility of naringenin, alone or in combination with beta-cyclodextrin.

  11. Formulation and biological evaluation of glimepiride-cyclodextrin-polymer systems.

    PubMed

    Ammar, H O; Salama, H A; Ghorab, M; Mahmoud, A A

    2006-02-17

    Glimepiride is one of the third generation sulfonylureas used for treatment of type 2 diabetes. Poor aqueous solubility and slow dissolution rate of the drug lead to irreproducible clinical response or therapeutic failure in some cases due to subtherapeutic plasma drug levels. Consequently, the rationale of this study was to improve the biological performance of this drug through enhancing its solubility and dissolution rate. Inclusion complexes of glimepiride in beta-cyclodextrin (beta-CyD), hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and sulfobutylether-beta-cyclodextrin (SBE-beta-CyD), with or without water soluble polymers were prepared by the kneading method. Binary systems were characterized by thermogravimetric analysis, IR spectroscopy and X-ray diffractometry. Phase solubility diagrams revealed increase in solubility of the drug upon cyclodextrin addition, showing A(p) type plot indicating high order complexation. All the ternary systems containing beta-CyD or HP-beta-CyD showed higher dissolution efficiency compared to the corresponding binary systems. The hypoglycemic effect of the most rapidly dissolving ternary system of glimepiride-HP-beta-CyD-PEG 4000 was evaluated after oral administration in diabetic rats by measuring blood glucose levels. The results indicated that this ternary system improves significantly the therapeutic efficacy of the drug. In conclusion, the association of water soluble polymers with glimepiride-CyD systems leads to great enhancement in dissolution rate, increased duration of action and improvement of therapeutic efficacy of the drug.

  12. Determination of enantiomeric amphetamines as metabolites of illicit amphetamines and selegiline in urine by capillary electrophoresis using modified beta-cyclodextrin.

    PubMed

    Heo, Y J; Whang, Y S; In, M K; Lee, K J

    2000-05-12

    The determination of enantiomeric amphetamine and methamphetamine in urine samples is important in order to distinguish use of the prescription drug selegiline (metabolized to R(-)-A and R(-)-MA) from the illicit use of S(+)-A and S(+)-MA. For the analysis of enantiomeric amphetamine (A) and methamphetamine (MA) in biological samples, the optimization of analytical condition was performed by capillary electrophoresis using chiral selectors including beta-cyclodextrin, carboxymethyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin. We have examined the factors to obtain the best chiral resolutions, separation efficiency and sensitivity, and wide concentration linearity. Optimum resolutions were achieved using 100 mM phosphate buffer, pH 2.5, containing 10 mM of carboxymethyl-beta-cyclodextrin. This method was applied for the quantitative determination of enantiomeric amphetamine and methamphetamine in urine samples obtained from patients taking illicit amphetamines or from rats and patients taking selegiline. Acceptable quantitative results in terms of resolution, precision, sensitivity and linearity were obtained from the real urine samples containing wide-ranging concentrations of A and MA by using two concentrations of internal standards, alpha(+)- (1 microg/ml) and beta-phenylethylamine (50 microg/ml).

  13. Theoretical and experimental study of inclusion complexes formed by isoniazid and modified β-cyclodextrins: 1H NMR structural determination and antibacterial activity evaluation.

    PubMed

    Teixeira, Milena G; de Assis, João V; Soares, Cássia G P; Venâncio, Mateus F; Lopes, Juliana F; Nascimento, Clebio S; Anconi, Cleber P A; Carvalho, Guilherme S L; Lourenço, Cristina S; de Almeida, Mauro V; Fernandes, Sergio A; de Almeida, Wagner B

    2014-01-09

    Me-β-cyclodextrin (Me-βCD) and HP-β-cyclodextrin (HP-βCD) inclusion complexes with isoniazid (INH) were prepared with the aim of modulating the physicochemical and biopharmaceutical properties of the guest molecule, a well-known antibuberculosis drug. The architectures of the complexes were initially proposed according to NMR data Job plot and ROESY followed by density functional theory (DFT) calculations of (1)H NMR spectra using the PBE1PBE functional and 6-31G(d,p) basis set, including the water solvent effect with the polarizable continuum model (PCM), for various inclusion modes, providing support for the experimental proposal. An analysis of the (1)H NMR chemical shift values for the isoniazid (H6',8' and H5',9') and cyclodextrins (H3,5) C(1)H hydrogens, which are known to be very adequately described by the DFT methodology, revealed them to be extremely useful, promptly confirming the inclusion complex formation. An included mode which describes Me-βCD partially enclosing the hydrazide group of the INH is predicted as the most favorable supramolecular structure that can be used to explain the physicochemical properties of the encapsulated drug. Antibacterial activity was also evaluated, and the results indicated the inclusion complexes are a potential strategy for tuberculosis treatment.

  14. Properties of cholesterol-reduced butter made with beta-cyclodextrin and added evening primrose oil and phytosterols.

    PubMed

    Kim, J J; Jung, T H; Ahn, J; Kwak, H S

    2006-12-01

    The present study was carried out to examine changes in the chemical and sensory properties of butter in which the cholesterol was reduced and to which evening primrose oil (EPO) and phytosterols were added. Crosslinked beta-cyclodextrin (beta-CD) made from adipic acid was used, and approximately 90% of the cholesterol was removed. The color measurement values "L" and "a" were significantly different between the control (butter with no beta-CD treatment and no added EPO and phytosterols) and treatment A (butter treated with 10% crosslinked beta-CD); however, the color values for "L" and "a" were similar. The color value "b" in treatment B (butter treated with 10% crosslinked beta-CD and 5% phytosterols and 3% EPO added) was significantly higher than in the other treatments. The thiobarbituric acid value of treatment B was significantly higher than that of the control and treatment A. Scores for hardness, elasticity, and cohesiveness were significantly lower in the control than in treatment A. Differences in sensory characteristics did not result from the beta-CD treatment but from the addition of EPO and phytosterols. In microscopic examinations, no noticeable differences were found among the treatments, and a smooth texture and a fine, uniform crystalline structure were observed. Results indicated that about 90% of the cholesterol was reduced by crosslinked beta-CD and that the beta-CD treatment itself did not adversely influence the chemical and sensory properties of the butter. However, the addition of EPO and phytosterols to the butter appeared to impair its sensory properties, especially in terms of rancidity and overall acceptability.

  15. 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.

  16. 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 ...

  17. 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%.

  18. Molecular encapsulation of rifampicin as an inclusion complex of hydroxypropyl-β-cyclodextrin: design; characterization and in vitro dissolution.

    PubMed

    He, Dan; Deng, Ping; Yang, Lin; Tan, Qunyou; Liu, Juan; Yang, Mei; Zhang, Jingqing

    2013-03-01

    A hydrophobic drug, rifampin (RFP), was molecularly encapsulated into hydroxylpropyl-β-cyclodextrin (HCD) to form a molecular inclusion complex (MRICD) with higher solubility and stability. A solid-state grinding method was applied to prepare MRICD for 0.5h. The inclusion ratio, binding constant and the change of Gibbs free energy estimated from the phase solubility diagram and/or by the ultraviolet-visible spectroscopic method were 1:1, ∼218 mol/L and -1.767 KJ/mol, respectively. Differential scanning calorimetry and Fourier transformed infrared spectra of MRICD confirmed the molecular interactions between RFP and HCD. Morphological differences between MICDH and RFP further confirmed the molecular encapsulation of RFP. The most probable configuration of MRICD was estimated via computer simulation. MRICD had a higher dissolution rate than free RFP. Weibull function fit well the dissolution data of MRICD. Broth macrodilution experiments indicated that MRICD had good antibacterial activity. MRICD might be a promising system for oral or parenteral drug delivery to treat bacterial infections.

  19. Physico-chemical characterization and in vitro/in vivo evaluation of loratadine:dimethyl-β-cyclodextrin inclusion complexes.

    PubMed

    Szabados-Nacsa, A; Sipos, P; Martinek, T; Mándity, I; Blazsó, G; Balogh, Á; Szabó-Révész, P; Aigner, Z

    2011-05-15

    A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in class II of the Biopharmaceutical Classification System, was investigated. It is an ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable. Inclusion complexes were prepared by kneading method, containing loratadine (LOR) and dimethyl-β-cyclodextrin (DIMEB) in two different molar ratios in an attempt to achieve better dissolution and therefore the better bioavailability of loratadine. The formation and physicochemical properties of the inclusion complexes were investigated by means of dissolution tests, pH-dependent solubility studies, electrospray ionization mass spectrometry and diffusion-ordered 1H NMR spectroscopy. The in vivo efficiency of the complexes was examined in rat animal experiments to confirm the better in vitro dissolution. The instrumental examinations proved the presence of total complexes in 1:1 ratio in both compositions. However, the in vitro pH-dependent solubility results, the in vivo blood levels and the greater pharmacological effect prove that excess DIMEB is needed to achieve the pH-independent and complete solubility of LOR, and therefore better and more consistent bioavailability.

  20. New Electrochemically-Modified Carbon Paste Inclusion β-Cyclodextrin and Carbon Nanotubes Sensors for Quantification of Dorzolamide Hydrochloride

    PubMed Central

    Alarfaj, Nawal Ahmad; El-Tohamy, Maha Farouk

    2016-01-01

    The present article introduces a new approach to fabricate carbon paste sensors, including carbon paste, modified carbon paste inclusion β-cyclodextrin, and carbon nanotubes for the quantification of dorzolamide hydrochloride (DRZ). This study is mainly based on the construction of three different carbon paste sensors by the incorporation of DRZ with phosphotungstic acid (PTA) to form dorzolamide-phosphotungstate (DRZ-PT) as an electroactive material in the presence of the solvent mediator ortho-nitrophenyloctyl ether (o-NPOE). The fabricated conventional carbon paste sensor (sensor I), as well as the other modified carbon paste sensors using β-cyclodextrin (sensor II) and carbon nanotubes (sensor III), have been investigated. The sensors displayed Nernstian responses of 55.4 ± 0.6, 56.4 ± 0.4 and 58.1 ± 0.2 mV·decade−1 over concentration ranges of 1.0 × 10−5–1.0 × 10−2, 1.0 × 10−6–1.0 × 10−2, and 5.0 × 10−8–1.0 × 10−2 mol·L−1 with lower detection limits of 5.0 × 10−6, 5.0 × 10−7, and 2.5 × 10−9 mol·L−1 for sensors I, II, and III, respectively. The critical performance of the developed sensors was checked with respect to the effect of various parameters, including pH, selectivity, response time, linear concentration relationship, lifespan, etc. Method validation was applied according to the international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use ICH guidelines. The developed sensors were employed for the determination of DRZ in its bulk and dosage forms, as well as bio-samples. The observed data were statistically analyzed and compared with those obtained from other published methods. PMID:27918458

  1. New Electrochemically-Modified Carbon Paste Inclusion β-Cyclodextrin and Carbon Nanotubes Sensors for Quantification of Dorzolamide Hydrochloride.

    PubMed

    Alarfaj, Nawal Ahmad; El-Tohamy, Maha Farouk

    2016-12-02

    The present article introduces a new approach to fabricate carbon paste sensors, including carbon paste, modified carbon paste inclusion β-cyclodextrin, and carbon nanotubes for the quantification of dorzolamide hydrochloride (DRZ). This study is mainly based on the construction of three different carbon paste sensors by the incorporation of DRZ with phosphotungstic acid (PTA) to form dorzolamide-phosphotungstate (DRZ-PT) as an electroactive material in the presence of the solvent mediator ortho-nitrophenyloctyl ether (o-NPOE). The fabricated conventional carbon paste sensor (sensor I), as well as the other modified carbon paste sensors using β-cyclodextrin (sensor II) and carbon nanotubes (sensor III), have been investigated. The sensors displayed Nernstian responses of 55.4 ± 0.6, 56.4 ± 0.4 and 58.1 ± 0.2 mV·decade(-1) over concentration ranges of 1.0 × 10(-5)-1.0 × 10(-2), 1.0 × 10(-6)-1.0 × 10(-2), and 5.0 × 10(-8)-1.0 × 10(-2) mol·L(-1) with lower detection limits of 5.0 × 10(-6), 5.0 × 10(-7), and 2.5 × 10(-9) mol·L(-1) for sensors I, II, and III, respectively. The critical performance of the developed sensors was checked with respect to the effect of various parameters, including pH, selectivity, response time, linear concentration relationship, lifespan, etc. Method validation was applied according to the international conference on harmonisation of technical requirements for registration of pharmaceuticals for human use ICH guidelines. The developed sensors were employed for the determination of DRZ in its bulk and dosage forms, as well as bio-samples. The observed data were statistically analyzed and compared with those obtained from other published methods.

  2. Photophysics of 4-( N, N-dimethylamino)cinnamaldehyde/α-cyclodextrin inclusion complex

    NASA Astrophysics Data System (ADS)

    Panja, Subhasis; Chakravorti, Sankar

    2002-01-01

    This paper reports the probing of α-cyclodextrin (α-CD) cavities with the help of dual emission properties of 4- N, N dimethylamino cinnamaldehyde (DMACA) in aqueous solution. An interesting feature could be observed that due to 1:1 complexation DMACA is encapsulated within α-CD in two distinctly different types of orientation as revealed from the relative positions and the intensity of locally excited state localized within donor and acceptor subunits (LE) and twisted intramolecular charge transfer (TICT) bands. In one situation the dimethylamino group is directed towards the larger rim of the cavity and in other the orientation is just the opposite. The different types of complexes were found to be excited selectively in different wavelength regions.

  3. Kinetic and physical-chemical study of the inclusion complex of β-cyclodextrin containing carvacrol

    NASA Astrophysics Data System (ADS)

    Menezes, Paula dos Passos; Serafini, Mairim Russo; de Carvalho, Yasmim Maria Barbosa Gomes; Soares Santana, Dayanne Valéria; Lima, Bruno Santos; Quintans-Júnior, Lucindo José; Marreto, Ricardo Neves; de Aquino, Thiago Mendonça; Sabino, Adilson Rodrigues; Scotti, Luciana; Scotti, Marcus Tullius; Grangeiro-Júnior, Severino; de Souza Araújo, Adriano Antunes

    2016-12-01

    Carvacrol is a good natural antimicrobial and antioxidant agent; however, its poor aqueous solubility and high volatility limit its application in food systems. Different methods of complexation have been used to preserve aromas in food products and complexation in cyclodextrins (CDs) is among the most efficient ways. In the present study, we investigated the complexation efficiency of carvacrol in β-CD using methods different from those already reported in the literature for this compound. The supramolecular structure of the carvacrol/β-CD complex was investigated by means of X-ray diffraction (XRD), Nuclear magnetic resonance (NMR), docking, complexation efficiency, thermogravimetry/derivate thermogravimetry (TG/DTG) and Karl Fischer titration. Results clearly showed the formation of a supramolecular complex in which the guest molecule, carvacrol, was entrapped inside the cavity of the host, β-CD mainly by slurry method. These results contribute to other studies involving this type of system.

  4. 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.

  5. 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.

  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. 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.

  8. Physico-chemical characterization and antibacterial activity of inclusion complexes of Hyptis martiusii Benth essential oil in β-cyclodextrin.

    PubMed

    Andrade, Tatianny A; Freitas, Thiago S; Araújo, Francielly O; Menezes, Paula P; Dória, Grace Anne A; Rabelo, Alessandra S; Quintans-Júnior, Lucindo J; Santos, Márcio R V; Bezerra, Daniel P; Serafini, Mairim R; Menezes, Irwin Rose A; Nunes, Paula Santos; Araújo, Adriano A S; Costa, Maria S; Campina, Fábia F; Santos, Antonia T L; Silva, Ana R P; Coutinho, Henrique D M

    2017-02-19

    Cyclodextrins (CDs) have been used as important pharmaceutical excipients for improve the physicochemical properties of the drugs of low solubility as the essential oil of Hyptis martiusii. This oil is important therapeutically, but the low solubility and bioavailability compromises your use. Therein, the aim of this study was to obtain and to characterize physico-chemically the samples obtained by physical mixture (PM), paste complexation (PC) and slurry complexation (SC) of the essential oil Hyptis martiusii (EOHM) in β-CD, and to compare the antibacterial and modulatory-antibiotic activity of products obtained and oil free. The physicochemical characterization was performed by differential scanning calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Karl Fischer titration. Additionally, the antibacterial tests were performed by microdilution technique. Thus, it was observed that the PM method showed low complexing capacity, unlike PC and SC in which it was observed the formation of inclusion complexes. In addition, the second stage of the TG/DTG curves showed that SC was the best method inclusion with mass loss of 6.9% over the PC that was 6.0%. The XRD results corroborate with the results above suggesting the formation of new solid phase and the SEM photomicrographs showed the porous surface of the samples PC and SC. The essential oil alone demonstrated an antibacterial and modulatory effect against the S. aureus and the Gram negative strain, respectively. However, the β-CD and the inclusion complex did not demonstrate any biological activity in the performed antibacterial assays.

  9. N-phenyl-1-naphthylamine/β-cyclodextrin inclusion complex as a new fluorescent probe for rapid and visual detection of Pd2+

    NASA Astrophysics Data System (ADS)

    Maniyazagan, Munisamy; Mohandoss, Sonaimuthu; Sivakumar, Krishnamoorthy; Stalin, Thambusamy

    2014-12-01

    Inclusion complex between N-phenyl-1-naphthylamine (NPN) and β-cyclodextrin (β-CD) was studied by FT-IR, 1H and 2D NMR, XRD, FT-Raman, SEM and DSC techniques. The formation of 1:1 stoichiometric inclusion complex of NPN with β-CD was proposed based on the Nuclear magnetic resonance spectroscopy and Molecular docking study. The molecular encapsulation of host-guest inclusion complex based on simple chemosensor has high selectivity and sensitivity for the determination of Pd2+ ion. Host-guest inclusion complex as a spectroscopic probe is used for the detection of transition metal cation Pd2+. Coordination of this Pd2+ with (NPN/β-CD) inclusion complex exhibited a noticeable color change in the solution state it used for naked-eye detection.

  10. DSC, X-ray and FTIR studies of a gemfibrozil/dimethyl-β-cyclodextrin inclusion complex produced by co-grinding.

    PubMed

    Aigner, Z; Berkesi, O; Farkas, G; Szabó-Révész, P

    2012-01-05

    The steps of formation of an inclusion complex produced by the co-grinding of gemfibrozil and dimethyl-β-cyclodextrin were investigated by differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD) and Fourier transform infrared (FTIR) spectroscopy with curve-fitting analysis. The endothermic peak at 59.25°C reflecting the melting of gemfibrozil progressively disappeared from the DSC curves of the products on increase of the duration of co-grinding. The crystallinity of the samples too gradually decreased, and after 35min of co-grinding the product was totally amorphous. Up to this co-grinding time, XRPD and FTIR investigations indicated a linear correlation between the cyclodextrin complexation and the co-grinding time. After co-grinding for 30min, the ratio of complex formation did not increase. These studies demonstrated that co-grinding is a suitable method for the complexation of gemfibrozil with dimethyl-β-cyclodextrin. XRPD analysis revealed the amorphous state of the gemfibrozil-dimethyl-β-cyclodextrin product. FTIR spectroscopy with curve-fitting analysis may be useful as a semiquantitative analytical method for discriminating the molecular and amorphous states of gemfibrozil.

  11. 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.

  12. 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.

  13. 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 (400 mg/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 0-100 mg/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 4 mg/mL for both systems and higher stability constant for anionic bβCDs than cationic derivatives.

  14. Valsartan inclusion by methyl-β-cyclodextrin: thermodynamics, molecular modelling, Tween 80 effect and evaluation.

    PubMed

    Chadha, Renu; Bala, Madhu; Arora, Poonam; Jain, D V S; Pissurlenkar, Raghuvir R S; Coutinho, Evans C

    2014-03-15

    The rationale of present study is to investigate the effect of Tween 80 on encapsulation ability of valsartan (VAL) by methyl-β-cyclodextrin (M-β-CD) and to determine the exact mode of binding. Phase solubility studies indicated 1:1 stoichiometry between VAL and M-β-CD both in the presence and absence of Tween 80. The NMR and molecular modelling studies indicated the insertion of both aromatic and aliphatic regions of VAL into the M-β-CD cavity suggesting the coexistence of two 1:1 complexes in equilibrium with each other. The stability constants, K1 (aromatic) and K2 (aliphatic), were enhanced in the presence of Tween 80 as evident by higher value of stability constants (K1 1992.0M(-1), K2 1864.0M(-1)) for ternary system in comparison to binary system (K1 1741.6M(-1), K2 1499.2M(-1)). Efficacy of ternary complex was established by significant decrease in the systolic blood pressure of deoxycorticosterone acetate (DOCA) induced hypertensive rats.

  15. 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.

  16. Thermoresponsive Delivery of Paclitaxel by β-Cyclodextrin-Based Poly(N-isopropylacrylamide) Star Polymer via Inclusion Complexation.

    PubMed

    Song, Xia; Wen, Yuting; Zhu, Jing-Ling; Zhao, Feng; Zhang, Zhong-Xing; Li, Jun

    2016-12-12

    Paclitaxel (PTX), a hydrophobic anticancer drug, is facing several clinical limitations such as low bioavailability and drug resistance. To solve the problems, a well-defined β-cyclodextrin-poly(N-isopropylacrylamide) star polymer was synthesized and used as a nanocarrier to improve the water solubility and aim to thermoresponsive delivery of PTX to cancer cells. The star polymer was able to form supramolecular self-assembled inclusion complex with PTX via host-guest interaction at room temperature, which is below the low critical solution temperature (LCST) of the star polymer, significantly improving the solubilization of PTX. At body temperature (above LCST), the phase transition of poly(N-isopropylacrylamide) segments induced the formation of nanoparticles, which greatly enhanced the cellular uptake of the polymer-drug complex, resulting in efficient thermoresponsive delivery of PTX. In particular, the polymer-drug complex exhibited better antitumor effects than the commercial formulation of PTX in overcoming the multi-drug resistance in AT3B-1 cells.

  17. 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.

  18. Gemcitabine and γ-cyclodextrin/docetaxel inclusion complex-loaded liposome for highly effective combinational therapy of osteosarcoma.

    PubMed

    Sun, Liang; Zhou, Dong-Sheng; Zhang, Peng; Li, Qing-Hu; Liu, Ping

    2015-01-15

    The aim of the present investigation was to formulate a docetaxel (DTX) and gemcitabine (GEM) co-loaded PEGylated liposome (DTX/GEM-L) to increase the therapeutic efficacy in osteosarcoma (OS). 2-Hydroxypropyl-γ-cyclodextrin/DTX inclusion complex was made to increase DTX aqueous solubility. DTX/GEM-L was characterized for morphological shape and size parameters. Release study showed a sustained release pattern for both the drugs. The nanocarriers based combinational drug significantly increased the cytotoxic effect than the free drug combination at the same concentration. The cell cycle analysis showed a predominant G2/M phase arrest for combinational drug. Importantly, more than 20% of cells were in late apoptosis chamber for DTX/GEM-L treatment with significant proportion of cells in the early apoptosis and necrotic phases. The antitumor efficacy was tested in MG63 cancer cell bearing xenograft nude mice. Results showed that DTX/GEM-L significantly reduced the tumor burden comparing to that of free combination cocktail. The PEGylated liposome successfully delivered the anticancer drugs in the osteosarcoma tumor interstitial spaces via EPR effect. DTX/GEM-L showed excellent safety profile along with the remarkable tumor suppression ability. Overall, results suggest that nanocarriers-based delivery system remarkably enhanced the apoptosis and cytotoxicity and increased the potency of combinational drug regimen.

  19. Permeability Profiles and Intestinal Toxicity Assessment of Hydrochlorothiazide and Its Inclusion Complex with β-Cyclodextrin Loaded into Chitosan Nanoparticles.

    PubMed

    Onnainty, R; Schenfeld, E M; Petiti, J P; Longhi, M R; Torres, A; Quevedo, M A; Granero, G E

    2016-11-07

    Here, a novel drug delivery system was developed for the hydrochlorothiazide (HCT):β-cyclodextrin (βCD) inclusion complex loaded into chitosan (CS) nanoparticles (NPs) [CS/HCT:βCD NPs]. It was found, for the first time, that exposure of the intestinal mucosa to free HCT resulted in an increased and abnormal intestinal permeability associated with several injuries to the intestinal epithelium. Nevertheless, the HCT delivery system obtained ameliorated the damage of the intestinal epithelium induced by HCT. Furthermore, we found that the corresponding permeability profiles for both the free HCT and the CS/HCT:βCD NPs were exponential and lineal, respectively. We propose that the increased intestinal uptake and severe tissue injury of HCT to the intestinal epithelium could be directly related to possible effects of this drug on the ionoregulatory Na(+/)K(+)-ATPase channel. Thus, it is postulated that the CS/HCT:βCD NPs may increase the gastrointestinal retention of the HCT, which would provide increased adherence to the mucus barrier that lines the intestinal epithelium; consequently, this would act as a slow HCT release delivery system and maintain lower drug levels of luminal gut in comparison with the administration of free HCT, leading to less severe local injury.

  20. [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.

  1. Analysis of some metabolites of organic solvents in urine by high-performance liquid chromatography with beta-cyclodextrin.

    PubMed

    Moon, D H; Paik, N W; Shim, Y B

    1997-07-04

    Chromatographic separation of the metabolites derived from toluene, ethylbenzene, styrene and xylene was carried out on untreated urine samples from factory workers. The elution sequence was as follows: phenylglyoxilic acid, 3-hydroxy-2-butanone, hippuric acid, o-methylhippuric acid, p-methylhippuric acid, m-methylhippuric acid, p-cresol, m-cresol and o-cresol. The stability constants (K(G)) of cresol and methylhippuric acid derivatives were evaluated. The capacity factor (k'), selectivity factor (alpha) and resolution (Rs) are described with a variety of mobile phases containing beta-cyclodextrin (beta-CD). The optimum concentration ratio of ethanol-water-acetic acid-beta-CD was determined to be 20:80:0.3:1.4%. Under these conditions, k' values of the five metabolites were 2

  2. Optimization of a simple method for the chiral separation of methamphetamine and related compounds in clandestine tablets and urine samples by beta-cyclodextrine modified capillary electrophoresis: a complementary method to GC-MS.

    PubMed

    Liau, An-Shu; Liu, Ju-Tsung; Lin, Li-Chan; Chiu, Yu-Chih; Shu, You-Ren; Tsai, Chung-Chen; Lin, Cheng-Huang

    2003-06-24

    The chiral separation of (+/-)-methamphetamine, (+/-)-methcathinone, (+/-)-ephedrine and (+/-)-pseudoephedrine by means of beta-cyclodextrine modified capillary electrophoresis is described. The distribution of enantiomers in clandestine tablets and urine samples were identified. Several electrophoretic parameters such as the concentration of beta-cyclodextrin, temperature, the applied voltage and the amount of organic solvent required for successful separation were optimized. The method, as described herein, represents a good complementary method to GC-MS for use in forensic and clinical analysis.

  3. Using inclusion complexes with cyclodextrins to explore the aggregation behavior of a ruthenium metallosurfactant.

    PubMed

    Iza, Nerea; Guerrero-Martínez, Andrés; Tardajos, Gloria; Ortiz, María José; Palao, Eduardo; Montoro, Teresa; Radulescu, Aurel; Dreiss, Cécile A; González-Gaitano, Gustavo

    2015-03-10

    The aggregation behavior of a chiral metallosurfactant, bis(2,2'-bipyridine)(4,4'-ditridecyl-2,2'-bipyridine)ruthenium(II) dichloride (Ru2(4)C13), synthesized as a racemic mixture was characterized by small-angle neutron scattering, light scattering, NMR, and electronic spectroscopies. The analysis of the SANS data indicates that micelles are prolate ellipsoids over the range of concentrations studied, with a relatively low aggregation number, and the micellization takes place gradually with increasing concentration. The presence of cyclodextrins (β-CD and γ-CD) induces the breakup of the micelles and helps to establish that micellization occurs at a very slow exchange rate compared to the NMR time scale. The open structure of this metallosurfactant enables the formation of very stable complexes of 3:1 stoichiometry, in which one CD threads one of the hydrocarbon tails and two CDs the other, in close contact with the polar head. The complex formed with β-CD, more stable than the one formed with the wider γ-CD, is capable of resolving the Δ and Λ enantiomers at high CD/surfactant molar ratios. The chiral recognition is possible due to the very specific interactions taking place when the β-CD covers-via its secondary rim-part of the diimine moiety connected to the hydrophobic tails. A SANS model comprising a binary mixture of hard spheres (complex + micelles) was successfully used to study quantitatively the effect of the CDs on the aggregation of the surfactant.

  4. Encapsulation of isohexenylnaphthazarins in cyclodextrins.

    PubMed

    Assimopoulou, A N; Papageorgiou, V P

    2004-05-01

    Naturally occurring isohexenylnaphthazarins (IHN), such as Alkannin, Shikonin (A/S) and their derivatives, are potent pharmaceutical substances with a wide spectrum of biological activity. In the present study, inclusion complexes of alkannin and shikonin commercial samples and IHN derivatives in the form of an oily extract of Alkanna tinctoria roots were formed with beta-cyclodextrin (CD) and beta-HPCD. These complexes were investigated to evaluate the effect of complexation on their aqueous solubility, decoloration, and also the percentage of polymeric A/S and IHN derivatives enclosed in the CDs cavity, since these decrease the active monomeric IHN. Both beta-CD and beta-HPCD increased the aqueous solubility of A/S and IHN derivatives and thus inclusion complexes can be used as drug delivery systems for A/S in both internal (capsules, tablets) and external hydrophilic pharmaceutical and cosmetic preparations (creams, gels, sprays) with enhanced bioavailability. The inclusion complexes formed had a pale purple colour, contributing to the partial decoloration of the A/S and thus of the fi nal pharmaceutical preparations. Finally, CDs selectively included more monomeric and less polymeric IHN, compared with the initial each time sample that is encapsulated; thus inclusion complexes may present enhanced biological activity.

  5. Study of the inclusion of the (R)- and (S)-camphor enantiomers in alpha-cyclodextrin by X-ray crystallography and molecular dynamics.

    PubMed

    Kokkinou, Areti; Tsorteki, Frantzeska; Karpusas, Michael; Papakyriakou, Athanasios; Bethanis, Kostas; Mentzafos, Dimitris

    2010-05-27

    The inclusion of (R)- and (S)-camphor compounds in alpha-cyclodextrin has been studied by X-ray crystallography. The crystal structures of the complexes reveal that one guest molecule is accommodated inside the cavity formed by a head-to-head cyclodextrin dimer. In the crystal lattice, the dimers form layers which are successively shifted by half a dimer. In both (R)- and (S)-cases, the camphor molecule exhibits disorder and occupies three major sites with orientations that can be described as either 'polar' or 'equatorial'. Molecular dynamics simulations performed for the observed complexes indicate that although the carbonyl oxygen of both (R)- and (S)-camphor switches between different hydrogen bonding partners, it maintains the observed mode of 'polar' or 'equatorial' alignment.

  6. Use of photoacoustic spectroscopy in the characterization of inclusion complexes of benzophenone-3-hydroxypropyl-β-cyclodextrin and ex vivo evaluation of the percutaneous penetration of sunscreen.

    PubMed

    Berbicz, Fernanda; Nogueira, Ana Claudia; Medina Neto, Antonio; Natali, Maria Raquel Marçal; Baesso, Mauro Luciano; Matioli, Graciette

    2011-10-01

    This work is aimed to evaluate the application of photoacoustic spectroscopy (PAS) in the characterization of inclusion complexes of benzophenone-3 (BZ-3) and hydroxypropyl-β-cyclodextrin (HPCD) and to analyze the ex vivo percutaneous penetration of sunscreens and their reaction with the skin. The formation of inclusion complexes of BZ-3 and HPCD was performed by co-precipitation in stoichiometric ratios of 1:1 and 1:2. Thermal analysis and PAS characterized these inclusion complexes, and they indicated that the stoichiometric ratio of 1:2 was best. Sunscreen formulations were prepared and applied on the ears of rabbits. PAS suggested that the formulation with the complex resulted in lower penetration of BZ-3. Histological analysis demonstrated that the use of the formulation with BZ-3 was associated with an increase in the comedogenic effect and the presence of acanthosis, while no such effect was found in the formulation with the complex. The formulation with the BZ-3-HPCD complex is a promising strategy for improving the photoprotective effect of BZ-3. PAS can be used in the study of inclusion complexes with cyclodextrins and the evaluation of the percutaneous penetration of sunscreen formulations. Further tests are being conducted using PAS to monitor in vivo changes in the optical absorption spectra of formulations and to investigate their photostability.

  7. SUPRAMOLECULAR COMPOSITE MATERIALS FROM CELLULOSE, CHITOSAN AND CYCLODEXTRIN: FACILE PREPARATION AND THEIR SELECTIVE INCLUSION COMPLEX FORMATION WITH ENDOCRINE DISRUPTORS

    PubMed Central

    Duri, Simon; Tran, Chieu D.

    2013-01-01

    We have successfully developed a simple and one step method to prepare high performance supramolecular polysaccharide composites from cellulose (CEL), chitosan (CS) and (2,3,6-tri-O-acetyl)-α-, β- and γ-cyclodextrin (α-, β- and γ-TCD). In this method, [BMIm+Cl−], an ionic liquid (IL), was used as a solvent to dissolve and prepare the composites. Since majority (>88%) of the IL used was recovered for reuse, the method is recyclable. XRD, FT-IR, NIR and SEM were used to monitor the dissolution process and to confirm that the polysaccharides were regenerated without any chemical modifications. It was found that unique properties of each component including superior mechanical properties (from CEL), excellent adsorbent for pollutants and toxins (from CS) and size/structure selectivity through inclusion complex formation (from TCDs) remain intact in the composites. Specifically, results from kinetics and adsorption isotherms show that while CS-based composites can effectively adsorb the endocrine disruptors (polychlrophenols, bisphenol-A), its adsorption is independent on the size and structure of the analytes. Conversely, the adsorption by γ-TCD-based composites exhibits strong dependency on size and structure of the analytes. For example, while all three TCD-based composites (i.e., α-, β- and γ-TCD) can effectively adsorb 2-, 3- and 4-chlorophenol, only γ-TCD-based composite can adsorb analytes with bulky groups including 3,4-dichloro- and 2,4,5-trichlorophenol. Furthermore, equilibrium sorption capacities for the analytes with bulky groups by γ-TCD-based composite are much higher than those by CS-based composites. Together, these results indicate that γ-TCD-based composite with its relatively larger cavity size can readily form inclusion complexes with analytes with bulky groups, and through inclusion complex formation, it can strongly adsorb much more analytes and with size/structure selectivity compared to CS-based composites which can adsorb the

  8. 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

  9. Supramolecular composite materials from cellulose, chitosan, and cyclodextrin: facile preparation and their selective inclusion complex formation with endocrine disruptors.

    PubMed

    Duri, Simon; Tran, Chieu D

    2013-04-23

    We have successfully developed a simple one-step method of preparing high-performance supramolecular polysaccharide composites from cellulose (CEL), chitosan (CS), and (2,3,6-tri-O-acetyl)-α-, β-, and γ-cyclodextrin (α-, β-, and γ-TCD). In this method, [BMIm(+)Cl(-)], an ionic liquid (IL), was used as a solvent to dissolve and prepare the composites. Because a majority (>88%) of the IL used was recovered for reuse, the method is recyclable. XRD, FT-IR, NIR, and SEM were used to monitor the dissolution process and to confirm that the polysaccharides were regenerated without any chemical modifications. It was found that unique properties of each component including superior mechanical properties (from CEL), excellent adsorption for pollutants and toxins (from CS), and size/structure selectivity through inclusion complex formation (from TCDs) remain intact in the composites. Specifically, the results from kinetics and adsorption isotherms show that whereas CS-based composites can effectively adsorb the endocrine disruptors (polychlrophenols, bisphenol A), their adsorption is independent of the size and structure of the analytes. Conversely, the adsorption by γ-TCD-based composites exhibits a strong dependence on the size and structure of the analytes. For example, whereas all three TCD-based composites (i.e., α-, β-, and γ-TCD) can effectively adsorb 2-, 3-, and 4-chlorophenol, only the γ-TCD-based composite can adsorb analytes with bulky groups including 3,4-dichloro- and 2,4,5-trichlorophenol. Furthermore, the equilibrium sorption capacities for the analytes with bulky groups by the γ-TCD-based composite are much higher than those by CS-based composites. Together, these results indicate that the γ-TCD-based composite with its relatively larger cavity size can readily form inclusion complexes with analytes with bulky groups, and through inclusion complex formation, it can strongly adsorb many more analytes and has a size/structure selectivity compared to

  10. 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

  11. Reversible heat-set organogel based on supramolecular interactions of beta-cyclodextrin in N,N-dimethylformamide.

    PubMed

    Li, Yuanyuan; Liu, Jian; Du, Guangyan; Yan, Hui; Wang, Hongyao; Zhang, Huacheng; An, Wei; Zhao, Wenjing; Sun, Tao; Xin, Feiei; Kong, Li; Li, Yueming; Hao, Aiyou; Hao, Jingcheng

    2010-08-19

    This paper describes the first reversible, heat-set organogel based on the supramolecular interactions of beta-cyclodextrin (beta-CD). The gel was prepared by interaction of diphenylamine (DPA) with beta-CD and lithium chloride in N,N-dimethylformamide (DMF). In this gel system, DPA could be gelated in DMF as the temperature increased and then dissolved again as the temperature decreased. In the microscopic structure of gel, beta-CDs play a key role in the formation of nanorods and microfibers. Some important features of the gel were observed. (1) The system is a multicomponent solution, in which each of the four components is required for the organogelation property. (2) The system is a reversible, thermo-responsive organogel composed of small organic molecules. When the temperature is lower than T(gel), the gel transforms back into a solution. The reversible thermo-transition was confirmed by differential scanning calorimetry (DSC). The gel system is responsive to the concentration of LiCl. No gel was formed without LiCl. The stimuli responses of the system with other salts such as KCl and NaCl were weaker than with LiCl. (4) The system is responsive to the addition of guest molecules. The structures and sizes of the guest molecules could influence the gel formation. Generally, T(gel) decreased by adding guest molecules in the gel system, but some guest molecules, whose structures are exactly fitted to the cavity of CDs, could prevent gel formation. This work may provide new avenues in delivery of functional molecules as well as design of intelligent materials and biomaterials.

  12. 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.

  13. Controlling the association of adamantyl-substituted poly{N-[tris(hydroxymethyl)methyl]acrylamide} and a beta-cyclodextrin/epichlorohydrin polymer by a small drug molecule--naproxen.

    PubMed

    Mislovicová, Danica; Kogan, Grigorij; Gosselet, Noëlle Martine; Sébille, Bernard; Soltés, Ladislav

    2007-01-01

    Two polymeric substances, a poly{N-[tris(hydroxymethyl)methyl]acrylamide} (THMMA) substituted with adamantyl moieties and a beta-cyclodextrin/epichlorohydrin polycondensate, formed a host-guest type complex, which resulted in the gel formation upon mixing of these two compounds at appropriate conditions. Introduction of a drug molecule, i.e., naproxen, that was able to fill the beta-cyclodextrin cavities, thus expulsing adamantyl moieties, led to disruption of such association and inhibition of gel formation. The conditions required for the association of the two polymeric components and formation of the gel, as well as the dynamics of its inhibition by addition of naproxen was established. The procedure of using solutions of two associating polymers and an appropriate drug competitor can be used at targeted viscosupplementation.

  14. Nonlinear enhancement of oxygen evolution in thylakoid membranes: modeling the effect of light intensity and beta-cyclodextrin concentration.

    PubMed

    Fragata, Mário; Dudekula, Subhan

    2005-08-04

    Electron transport through photosystem II, measured as oxygen evolution (OE), was investigated in isolated thylakoid membranes treated with beta-cyclodextrin (beta-CD, a cyclic oligosaccharide constituted of seven alpha-d-glucose residues linked by alpha-1,4 glycosidic bonds) and irradiated with white light of variable intensity. First, we found that the light-response curves of oxygen evolution are well fitted with a hyperbolic function, the shape of which is not affected by the beta-CD concentration. Second, we showed that under conditions of irradiation with white light of saturating intensity ( approximately 5000 mumol of photons/m(2).s) beta-CD enhances the oxygen evolution in the thylakoid membranes according to a sigmoid function displaying a sharp inflection point, or transition. Unexpectedely, this beta-CD effect is not observed at irradiances of less than approximately 300 mumol of photons/m(2).s. We attempted a theoretical analysis of the combined effect of irradiance and beta-CD concentration on oxygen evolution (OE(th)). For this purpose, the effect of irradiance (I) was modeled with a hyperbola (i) and the beta-CD concentration (C) contribution with a Hill equation, that is, a sigmoid function (ii). The mathematical simulations generated the following general expressions: (i) OE(th) = [OE(max)(0) G(1)(C)]I/[L(1/2)(0) G(2)(C) + I] and (ii) G(i)()(C) = 1 + p[C(n)()/(K(1/2)(n)() + C(n)())], where OE(max)(0) is the OE maximum (OE(max)) in the absence of beta-CD, L(1/2)(0) is the photon flux density giving OE(max)/2 in the absence of beta-CD, G(1)(C) or G(2)(C) is obtained from G(i)()(C) where i is 1 or 2, n is the Hill coefficient, p is a parameter to account for the beta-CD-mediated maximum OE increase, and K(1/2) is the beta-CD concentration giving half-maximal OE activity. The results of the calculations yielded the expression (iii) OE(th) = 151[1 + 3.3C(4.8)/(13.1(4.8) + C(4.8))]I/{97.5[1 + 5.2C(7.8)/(14.8(7.8) + C(7.8))] + I} which agrees well with

  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.

  16. Effects of methyl-beta-cyclodextrin treatment on secretion profile of interferon-beta and zonula occuludin-1 architecture in Madin-Darby canine kidney cell monolayers.

    PubMed

    Maruyama, Masato; Ishida, Kayo; Watanabe, Yoshihiko; Nishikawa, Makiya; Takakura, Yoshinobu

    2009-05-01

    The interferon (IFN) is a paradigm of secretory protein. However, it has been poorly understood how its secretion is regulated in polarized epithelial cells. Recently, we had shown that exogenous IFNs transiently expressed in polarized monolayers were predominantly secreted to the side on which gene transfection had been performed, while stably expressed IFNs were secreted almost equally to the both cell sides. Since those modes of secretion did not affect each other, epithelial cell layers seemed to have at least two protein sorting/secretion pathways, one for transient expression and the other for stable expression, for identical secretory proteins. Furthermore, this dual secretion profile seemed to be mediated by distinct post-trans Golgi network vesicles, suggesting the involvement of lipid rafts in the sorting multiplicity. To address this issue, here we studied the effects of cholesterol depletion with methyl-beta-cyclodextrin (MbetaCD) on the secretion profile of IFN-beta exogenously expressed in Madin-Darby canine kidney (MDCK) cells. The MbetaCD-treatment, however, did not affect the profile in either transient or stable expression, although the architecture of zonula occuludin-1, which links to the tight junction, was substantially disrupted by the treatment. Further analysis of Triton X-100-insoluble cell extracts by sucrose density centrifugation demonstrated that IFN-beta was not apparently associated with lipid rafts in either transient or stable expression. These results suggest that lipid rafts may not be crucially involved in the regulation of secretion polarity of IFN-beta in the epithelial cells.

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

    PubMed

    Izadmanesh, Y; Ghasemi, Jahan B

    2016-08-05

    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.

  18. 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.

  19. Phase Structure and Properties of a Biodegradable Block Copolymer Coalesced from It's Crystalline Inclusion Compound Formed with alpha-Cyclodextrin

    NASA Astrophysics Data System (ADS)

    Shuai, Xintao; Wei, Min; Probeni, Francis; Bullions, Todd A.; Shin, I. Daniel; Tonelli, Alan E.

    2002-03-01

    A well-defined biodegradable block copolymer of poly(epsilon caprolactone) (PCL) and poly(L-lactic acid) (PLLA) was synthesized and characterized and then included as a guest in an inclusion compound (IC) formed with the host alpha-cyclodextrin (CD). The PCL-b-PLLA block copolymer was subsequently coalesced from it's CD-IC crystals by either treatment with hot water (50 C) or an aqueous amylase solution at 25 C. The coalesced PCL-b-PLLA was examined by FTIR, DSC, TGA, and WAXD and was found to be much more homogeneosly organized, with much less segregation and crystallinity of the PCL and PLLA microphases. The morpholgy, crystallization kinetics, thermal behavior, and biodegradability of the coalesced PCL-b-PLLA block copolymer was studied by comparison to similar observations made on as-synthesized PCL-b-PLLA, PCL and PLLA homopolymers, and their solution-cast blend. The PCL and PLLA blocks are found to be more intimately mixed, with less phase segregation, in the coalesced diblock copolymer, and this leads to homogeneous bulk crystallization, which is not observed for the as-synthesized diblock copolymer. The coalesced PCL-b-PLLA was also found to be more quickly biodegraded (lipase from Rhizopus arrhizus)than the as-synthesized PCL-b-PLLA or the physical blend of PCL and PLLA homopolymers. Overall, the coalescence of the inherently phase segregated diblock copolymer PCL-b-PLLA results in a small amount of compact, chain-extended PCL and PLLA crystals embedded in an amorphous phase, largely consisting of well-mixed PCL and PLLA blocks. Thus, we have demonstrated that it is possible to control the morpholgy of a biodegradable diblock copolymer, thereby significantly modifying it's properties, by coalescence from it's CD-IC crystals.

  20. 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

  1. 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.

  2. Impact of chlorpromazine self-association on its apparent binding constants with cyclodextrins: Effect of SBE(7)-beta-CD on the disposition of chlorpromazine in the rat.

    PubMed

    McIntosh, Michelle P; Leong, Nathania; Katneni, Kasiram; Morizzi, Julia; Shackleford, David M; Prankerd, Richard J

    2010-07-01

    Chlorpromazine is an antipsychotic agent with poor aqueous solubility. Complexation with SBE(7)-beta-CD can aid intravenous delivery through increasing the apparent solubility of chlorpromazine. However, chlorpromazine has also been known to self-associate. This self-association can influence its capacity to interact with other chemical species, such as cyclodextrins. This study aimed to characterise the self-association and cyclodextrin binding properties of chlorpromazine, and the effect on pharmacokinetic parameters in rats when dosed with a SBE(7)-beta-CD containing formulation. Pharmacokinetic studies of chlorpromazine in the presence and absence of SBE(7)-beta-CD were undertaken in rats. The binding constant of SBE(7)-beta-CD and chlorpromazine was studied relative to chlorpromazine concentration via fluorescence. The self-association of chlorpromazine was studied by fluorescence and UV-visible spectrophotometry. Urinary excretion of intact chlorpromazine increased in the presence of SBE(7)-beta-CD. The SBE(7)-beta-CD binding constant of chlorpromazine is highly concentration dependent and the variation can be attributed to the self-association of chlorpromazine. The apparent binding constant of chlorpromazine is highest at pharmacologically relevant concentrations, providing an explanation for the significant increase in renal chlorpromazine excretion observed in rats.

  3. Synthesis of the novel β-cyclodextrin-chromophore inclusion compound and research on the electro-optic activity of its systems

    NASA Astrophysics Data System (ADS)

    Bo, Shuhui; Chen, Zhuo; Zhen, Zhen; Liu, Xinhou

    2011-10-01

    In the second order nonlinear (NLO) optics, interchromophore electrostatic interactions have been suggested as a major challenge of the poor efficiency in the poling induced polar order. In this article, we formed a β-cyclodextrinchromophore inclusion compound by embedding a dumb-bell shape chromophore in a β-cyclodextrin. Compared to hyperbranched chromophores, this inclusion compound could create a 360° steric hindrance and pull the distance between molecules. Then this inclusion compound could prevent chromophore aggregation and minimize the interactions which hamper higher nonlinear optical activity. The method of the refractive index for electro-optic materials which can determine the degree of chromophore aggregation in polymers was first proposed and confirmed in this work. These properties have provided a great promise in the fabrication of EO materials and devices.

  4. Characterization of aspartame-cyclodextrin complexation.

    PubMed

    Sohajda, Tamás; Béni, Szabolcs; Varga, Erzsébet; Iványi, Róbert; Rácz, Akos; Szente, Lajos; Noszál, Béla

    2009-12-05

    The inclusion complex formation of aspartame (guest) and various cyclodextrins (host) were examined using 1H NMR titration and capillary electrophoresis. Initially the protonation constants of aspartame were determined by NMR-pH titration with in situ pH measurement to yield log K1=7.83 and log K2=2.96. Based on these values the stability of the complexes formed by aspartame and 21 different cyclodextrins (CDs) were studied at pH 2.5, pH 5.2 and pH 9.0 values where aspartame exists predominantly in monocationic, zwitterionic and monoanionic form, respectively. The host cyclodextrin derivatives differed in various sidechains, degree of substitution, charge and purity so that the effect of these properties could be examined systematically. Concerning size, the seven-membered beta-cyclodextrin and its derivatives have been found to be the most suitable host molecules for complexation. Highest stability was observed for the acetylated derivative with a degree of substitution of 7. The purity of the CD enhanced the complexation while the degree of substitution did not provide obvious consequences. Finally, geometric aspects of the inclusion complex were assessed by 2D ROESY NMR and molecular modelling which proved that the guest's aromatic ring enters the wider end of the host cavity.

  5. 5-Fluorouracil acetic acid/beta-cyclodextrin conjugates: drug release behavior in enzymatic and rat cecal media.

    PubMed

    Udo, Koichi; Hokonohara, Kazuhiro; Motoyama, Keiichi; Arima, Hidetoshi; Hirayama, Fumitoshi; Uekama, Kaneto

    2010-03-30

    5-Fluorouracil-1-acetic acid (5-FUA) was prepared and covalently conjugated to beta-cyclodextrin (beta-CyD) through ester or amide linkage, and the drug release behavior of the conjugates in enzymatic solutions and rat cecal contents were investigated. The 5-FUA/beta-CyD ester conjugate was slowly hydrolyzed to 5-FUA in aqueous solutions (half lives (t(1/2))=38 and 17h at pH 6.8 and 7.4, respectively, at 37 degrees C), whereas the amide conjugate was hardly hydrolyzed at these physiological conditions, but hydrolyzed only in strong alkaline solutions (>0.1M NaOH) at 60 degrees C. Both ester and amide conjugates were degraded in solutions of a sugar-degrading enzyme, alpha-amylase, to 5-FUA/maltose and triose conjugates, but the release of 5-FUA was only slight in alpha-amylase solutions. In solutions of an ester-hydrolyzing enzyme, carboxylic esterase, the ester conjugate was hydrolyzed to 5-FUA at the same rate as that in the absence of the enzyme, whereas the amide conjugate was not hydrolyzed by the enzyme. On the other hand, 5-FUA was rapidly released when the ester conjugate was firstly hydrolyzed by alpha-amylase, followed secondly by carboxylic esterase. The results indicated that the ester conjugate was hydrolyzed to 5-FUA in a consecutive manner, i.e. it was firstly hydrolyzed to the small saccharide conjugates, such as the maltose conjugate, by alpha-amylase, and the resulting small saccharide conjugates having less steric hindrance was susceptible to the action of carboxylic esterase, giving 5-FUA. The in vitro release behavior of the ester conjugate was clearly reflected in the hydrolysis in rat cecal contents and in the in vivo release after oral administration to rats.

  6. Differentiating inclusion complexes from host molecules by tapping-mode atomic force microscopy.

    PubMed Central

    Muñoz-Botella, S; Martin, M A; del Castillo, B; Vázquez, L

    1996-01-01

    Tapping-mode atomic force microscopy imaging under different cantilever vibration amplitudes has been used to differentiate the host beta-cyclodextrin nanotubes from retinal/beta-cyclodextrin inclusion complex nanotubes. It was observed that both compounds were deformed differently by the applied probe force because of their different local rigidity. This change in the elasticity properties can be explained as a consequence of the inclusion process. This method shows that tapping-mode atomic force microscopy is an useful tool to map soft sample elasticity properties and to distinguish inclusion complexes from their host molecules on the basis of their different mechanical response. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:8804591

  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.

  8. Evaluation of various properties of alternative salt forms of sulfobutylether-beta-cyclodextrin, (SBE)7M-beta-CD.

    PubMed

    Sotthivirat, S; Haslam, J L; Stella, V J

    2007-02-07

    The goal of this study was to evaluate alternative salt forms of (SBE)7M-beta-CD (currently the sodium salt). The potential salt form would ideally decrease the rate of (SBE)7M-beta-CD release from osmotic pump formulations and result in an increase in the rate and extent of drug release in osmotic pump tablet and pellet dosage forms. Several (SBE)7M-beta-CD salt forms (potassium, calcium, and two ethylene diamine salt forms) were prepared by either titration or ultrafiltration and characterized by elemental analysis and capillary electrophoresis, CE. The physical properties (water uptake behavior, osmolality, complexation characteristics, etc.) were then compared to the sodium salt form. Although the water isotherm and the binding characteristics using various model drugs were similar among all the salt forms, the calcium salt form appeared to be the best alternative candidate due to its lower osmolality and slower intrinsic dissolution rate.

  9. A convenient synthesis of 7 alpha-hydroxycholest-4-en-3-one by the hydroxypropyl-beta-cyclodextrin-facilitated cholesterol oxidase oxidation of 3 beta,7 alpha-cholest-5-ene-3,7-diol.

    PubMed

    Alexander, D L; Fisher, J F

    1995-03-01

    The initial biosynthetic conversions of cholesterol to the bile acids involve sequential 7 alpha-hydroxylation (catalyzed by cholesterol 7 alpha-hydroxylase) followed by C-3 oxidation and concomitant double bond migration (to a delta 4-configuration, catalyzed by 3 beta-delta 5-C27-steroid oxidoreductase) to provide 7 alpha-hydroxycholest-4-en-3-one. A straightforward, and economical, preparation (on a 0.1 g scale) of this pivotal biosynthetic intermediate has been devised. Reduction of 3 beta-(benzoyloxy)-cholest-5-en-7-one with LiB(sec-butyl)3H provided a 4:1 mixture, respectively, of the 7 alpha- and 7 beta-hydroxy diastereomers, which were separated chromatographically. Solvolytic removal of the C-3 benzoyl group gave 3 beta,7 alpha-cholest-5-ene-3,7-diol. A suspension of the 1:1 (v/v) complex (formed by mutual dissolution in MeOH, followed by evaporation of the solvent) of this diol with hydroxypropyl-beta-cyclodextrin, at a concentration of 1 mg mL-1 (in neutral phosphate buffer), was converted by Brevibacterium sp cholesterol oxidase (0.25 U mg-1 of substrate) and catalase (70 U mg-1 of substrate, to recover O2 from the H2O2 produced by the enzymatic oxidation) to a suspension of 7 alpha-hydroxycholest-4-en-3-one and the hydroxypropyl-beta-cyclodextrin. The yield for the enzymatic conversion was in excess of 90%. A much poorer and less reproducible yield (< 20%) was seen in the absence of the hydroxypropyl-beta-cyclodextrin. Routine extraction of this aqueous suspension, and chromatographic purification (85:15 CHCl3/acetone v/v on silica) of the residue, gave pure 7 alpha-hydroxycholest-4-en-3-one in 68% isolated yield. This route is a significant improvement, in terms of reaction scale and convenience, over the previous procedures for the preparation of this steroid.

  10. Methyl-beta-cyclodextrin enhanced biodegradation of polycyclic aromatic hydrocarbons and associated microbial activity in contaminated soil.

    PubMed

    Sun, Mingming; Luo, Yongming; Christie, Peter; Jia, Zhongjun; Li, Zhengao; Teng, Ying

    2012-01-01

    The contamination of soils by polycyclic aromatic hydrocarbons (PAHs) is a widespread environmental problem and the remediation of PAHs from these areas has been a major concern. The effectiveness of many in situ bioremediation systems may be constrained by low contaminant bioavailability due to limited aqueous solubility or a large magnitude of sorption. The objective of this research was to evaluate the effect of methyl-beta-cyclodextrin (MCD) on bioaugmentation by Paracoccus sp. strain HPD-2 of an aged PAH-contaminated soil. When 10% (W/W) MCD amendment was combined with bioaugmentation by the PAH-degrading bacterium Paracoccus sp. strain HPD-2, the percentage degradation of total PAHs was significantly enhanced up to 34.8%. Higher counts of culturable PAH-degrading bacteria and higher soil dehydrogenase and soil polyphenol oxidase activities were observed in 10% (W/W) MCD-assisted bioaugmentation soil. This MCD-assisted bioaugmentation strategy showed significant increases (p < 0.05) in the average well color development (AWCD) obtained by the BIOLOG Eco plate assay, Shannon-Weaver index (H) and Simpson index (lambda) compared with the controls, implying that this strategy at least partially restored the microbiological functioning of the PAH-contaminated soil. The results suggest that MCD-aided bioaugmentation by Paracoccus sp. strain HPD-2 may be a promising practical bioremediation strategy for aged PAH-contaminated soils.

  11. Use of beta-cyclodextrin in the capillary zone electrophoretic separation of the components of clandestine heroin preparations.

    PubMed

    Macchia, M; Manetto, G; Mori, C; Papi, C; Di Pietro, N; Salotti, V; Bortolotti, F; Tagliaro, F

    2001-07-27

    The present paper describes the methodological optimization and validation of a capillary zone electrophoresis method for the rapid determination of heroin, secondary products and additives present in clandestine heroin samples, by using 20 mM beta-cyclodextrins in phosphate buffer, pH 3.23. Applied potential was 15 kV and separation temperature was 24 degrees C; detection was by UV absorption at 200 nm wavelength. Heroin samples were first dissolved in CHCl3-MeOH (96:4, v/v) and injected by pressure (0.5 p.s.i., 3 s; 1 p.s.i.=6894.76 Pa) after evaporation of the organic mixture and reconstitution in aqueous buffer. Under the described conditions, phenylethylamine (internal standard), morphine, monoacetylmorphine, heroin, acetylcodeine, papaverine, codeine and narcotine were baseline resolved in less than 10 min. The limit of detection was better than 1 microg/ml for each analyte. The study of the intra-day and day-to-day precision showed, in terms of migration times, RSDs < or = 0.71% and, in terms of peak areas, RSDs < or = 3.2%. Also, the evaluation of linearity and analytical accuracy of the method provided good results for all the analytes investigated, thus allowing its application to real cases of seized controlled drug preparations.

  12. Enantioselective determination of chlorpheniramine in various formulations by HPLC using carboxymethyl-beta-cyclodextrin as a chiral additive.

    PubMed

    Chen, Quan Cheng; Jeong, Su Jin; Hwang, Gwi Seo; Kim, Kyeong Ho; Kang, Jong Seong

    2008-04-01

    A chiral mobile phase HPLC method is described for chiral separation and determination of chlorpheniramine (CP) enantiomers in various commercial preparations. Chromatographic separation was achieved on a conventional ODS column with a mixture of aqueous sodium phosphate (5 mM) containing 0.5 mM carboxymethyl-beta-cyclodextrin, methanol and triethylamine (73:25:2, v/v/v, pH 4.3) as the mobile phase. The flow rate of isocratic elution was 0.24 mL/min and peaks were detected at 224 nm. The method was applied to nine commercial CP preparations in six dosage forms and CP enantiomers were well separated without any disturbance of other ingredients or impurities present. The results showed that only one preparation was d-CP and the others were dl-CP preparations. The contents of all the preparations were found to be in the range of 97%-104% of labeled contents. This method was economical and convenient, affording sufficient accuracy, precision and reproducibility, as well as sensitivity and selectivity.

  13. 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

  14. Pilot-scale electrokinetic movement of HCB and Zn in real contaminated sediments enhanced with hydroxypropyl-beta-cyclodextrin.

    PubMed

    Li, Taiping; Yuan, Songhu; Wan, Jinzhong; Lin, Li; Long, Huayun; Wu, Xiaofeng; Lu, Xiaohua

    2009-08-01

    This study deals with the efficiency of a pilot-scale electrokinetic (EK) treatment on real aged sediments contaminated with hexachlorobenzene (HCB) and Zn. A total of 0.5m(3) of sediments were treated under a constant voltage in a polyvinyl chloride reactor. The changes of sediment pH, electrical conductivity (EC), organic content (OC), the transport of contaminants in sediments and the consumption of electric energy were evaluated. After 100 d processing, sediment pH slightly increased compared with the initial values, particularly in the bottom layer close to cathodic section, while sediment EC in most sections significantly decreased. Sediment OC in all sections increased, which implied that hydroxypropyl-beta-cyclodextrin (HPCD) was successfully penetrated across sediments by electroosmosis. Significant movement of contaminants was observed across sediments with negligible removals. Both HCB and Zn generally moved from sections near anode and accumulated near cathode. Upon the completion of treatment, the electric energy consumption was calculated as 563 kWhm(-3). This pilot-scale EK test indicates that it is difficult to achieve great removal of hydrophobic organic compounds (HOCs), or HOCs and heavy metal mixed contaminants, by EK treatment in large scale with the use of HPCD.

  15. 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.

  16. Conformational Change in the Mechanism of Inclusion of Ketoprofen in β-Cyclodextrin: NMR Spectroscopy, Ab Initio Calculations, Molecular Dynamics Simulations, and Photoreactivity.

    PubMed

    Guzzo, T; Mandaliti, W; Nepravishta, R; Aramini, A; Bodo, E; Daidone, I; Allegretti, M; Topai, A; Paci, M

    2016-10-11

    Inclusion of drugs in cyclodextrins (CDs) is a recognized tool for modifying several properties such as solubility, stability, bioavailability, and so on. The photoreactive behavior of the β-CD/ketoprofen (KP) complex upon UV exposure showed a significant increase in photodecarboxylation, whereas the secondary degradation products by hydroxylation of the benzophenone moiety were inhibited. The results may account for an improvement of KP photophysical properties upon inclusion, thus better fostering its topical use. To correlate the structural details of the inclusion with these results, an NMR spectroscopic study of KP upon inclusion in β-CD was performed. Effects of the magnetically anisotropic centers of KP, changing their orientations upon inclusion and giving chemical shift variations, were specifically correlated with the results of the molecular dynamic simulations and ab initio calculations. In the large variety of papers focusing on the structural analysis of β-CD complexes, this work represents one of the few examples in which a detailed analysis of these simultaneous upfield-downfield NMR shifts of the same aromatic molecule upon inclusion is reported. Interestingly, the results demonstrate that the observed upfield and downfield shifts upon inclusion are not related to any direct magnetic role of β-CD. The conformational change of KP upon the inclusion process consists of a slight reduction in the angle between the two phenyl rings and in a remarkable reduction in the mobility of the carboxyl group, the latter being one of the main contributions to the NMR resonance shifts. These structural details help in understanding the features of the inclusion complex and, eventually, the driving force for its formation.

  17. 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.

  18. Modulation of photophysics due to orientational selectivity of 4- N, N-dimethylamino cinnamaldehyde β-cyclodextrin inclusion complex in different solvents

    NASA Astrophysics Data System (ADS)

    Panja, Subhasis; Ranjan Bangal, Prakriti; Chakravorti, Sankar

    2000-10-01

    This paper delineates some results on the twisted intramolecular charge transfer (TICT) dynamics of 4- N, N-dimethylamino cinnamaldehyde (DMACA) encapsulated in β-cyclodextrin in aqueous and non-aqueous solvents at room temperature. 4- N, N-Dimethylamino cinnamaldehyde is found to form a 1:1 inclusion complex with β-CD in both aqueous and non-aqueous solvents with a binding constant higher in aqueous solvent. The most important feature of the inclusion complexes of 4- N, N-dimethylamino cinnamaldehyde, as revealed from photophysics of normal and twisted intramolecular charge transfer bands, is that there is a preferential orientation of 4- N, N-dimethylamino cinnamaldehyde inside β-CD cavity in aqueous solvent with dimethyl group sticking outside and in non-aqueous solvents it is just the opposite.

  19. Inclusion complex of chrysin with sulfobutyl ether-β-cyclodextrin (Captisol®): Preparation, characterization, molecular modelling and in vitro anticancer activity

    NASA Astrophysics Data System (ADS)

    Kulkarni, Abhijeet D.; Belgamwar, Veena S.

    2017-01-01

    Present work demonstrates the impact of sulfobutyl ether-β-cyclodextrin (SBE-β-CD, Captisol®) complexation on the solubility, dissolution and pH stability of the poorly soluble polyphenol chrysin (CHR) by freeze-drying technique. Phase solubility indicated the 1:1 stoichiometry. FTIR, DSC, PXRD, and SEM analysis confirmed the formation of inclusion complex. Moreover, 1H NMR studies illustrated that the possible inclusion mode was through A-ring of the CHR which was further confirmed by molecular modelling. In addition, CHR/SBE-β-CD complex exhibited ∼108 times higher solubility and faster dissolution compared to CHR. The pH stability profile exhibited the protective effect of SBE-β-CD on the CHR at simulated pH. Also, in vitro cytotoxicity assay revealed an appreciable improvement in the anticancer activity of complex compared to free CHR, on MCF-7 and HeLa cell lines validating its superiority as a carrier.

  20. Intrathecal 2-Hydroxypropyl-Beta-Cyclodextrin in a Single Patient with Niemann-Pick C1

    PubMed Central

    Maarup, Timothy J.; Chen, Agnes H.; Porter, Forbes D.; Farhat, Nicole Y.; Ory, Daniel S.; Sidhu, Rohini; Jiang, Xuntian; Dickson, Patricia I.

    2015-01-01

    Niemann-Pick C, Type 1 (NPC1) is a progressive autosomal recessive neurologic disease caused by defective intracellular cholesterol and lipid trafficking. There are currently no United States Food and Drug Administration approved treatments for NPC1. We undertook a study evaluating the safety, efficacy, and biomarker response of intrathecal 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in a 12-year old subject with mildly symptomatic NPC. The subject received 200mg intrathecal HP-β-CD administered biweekly via lumbar puncture. To date the subject has received 27 intrathecal HP-β-CD injections. Intrathecal HP-β-CD has been generally safe and well tolerated in this subject. There has been improvement in vertical gaze. The subject has developed subclinical hearing loss at high frequency that is likely HP-β-CD related. Plasma 24-(S)-hydroxycholesterol, a pharmacodynamic biomarker for cholesterol redistribution in the central nervous system, was significantly increased in response to each of the first 5 drug administrations. Further dosing as well as dose escalations are needed to more completely ascertain the safety and efficacy of intrathecal HP-β-CD. PMID:26189084

  1. Direct administration of 2-Hydroxypropyl-Beta-Cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements.

    PubMed

    Lichtenhan, J T; Hirose, K; Buchman, C A; Duncan, R K; Salt, A N

    2017-01-01

    2-Hydroxypropyl-Beta-Cyclodextrin (HPβCD) can be used to treat Niemann-Pick type C disease, Alzheimer's disease, and atherosclerosis. But, a consequence is that HPβCD can cause hearing loss. HPβCD was recently found to be toxic to outer hair cells (OHCs) in the organ of Corti. Previous studies on the chronic effects of in vivo HPβCD toxicity did not know the intra-cochlear concentration of HPβCD and attributed variable effects on OHCs to indirect drug delivery to the cochlea. We studied the acute effects of known HPβCD concentrations administered directly into intact guinea pig cochleae. Our novel approach injected solutions through pipette sealed into scala tympani in the cochlear apex. Solutions were driven along the length of the cochlear spiral toward the cochlear aqueduct in the base. This method ensured that therapeutic levels were achieved throughout the cochlea, including those regions tuned to mid to low frequencies and code speech vowels and background noise. A wide variety of measurements were made. Results were compared to measurements from ears treated with the HPβCD analog methyl-β-cyclodextrin (MβCD), salicylate that is well known to attenuate the gain of the cochlear amplifier, and injection of artificial perilymph alone (controls). Histological data showed that OHCs appeared normal after treatment with a low dose of HPβCD, and physiological data was consistent with attenuation of cochlear amplifier gain and disruption of non-linearity associated with transferring acoustic sound into neural excitation, an origin of distortion products that are commonly used to objectively assess hearing and hearing loss. A high dose of HPβCD caused sporadic OHC losses and markedly affected all physiologic measurements. MβCD caused virulent destruction of OHCs and physiologic responses. Toxicity of HPβCD to OHC along the cochlear length is variable even when a known intra-cochlear concentration is administered, at least for the duration of our acute

  2. Preparation and Characterization of the Sulfobutylether-β-Cyclodextrin Inclusion Complex of Amiodarone Hydrochloride with Enhanced Oral Bioavailability in Fasted State.

    PubMed

    Wang, Dandan; Chen, Guoguang; Ren, Lili

    2016-10-18

    Amiodarone hydrochloride (AMD) is used in the treatment of a wide range of cardiac tachyarrhythmias, including both ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT). The objectives of this study were to improve the solubility and bioavailability in fasted state and to reduce the food effect of AMD by producing its inclusion complex with sulfobutylether-β-cyclodextrin (SBE-β-CD). The complex was prepared through a saturated water solution combined with the freeze-drying method and then characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and differential scanning calorimetry. The solubilities of AMD and its complex were 0.35 and 68.62 mg/mL, respectively, and the value of the inclusion complex was significantly improved by 196-fold compared with the solubility of free AMD. The dissolution of the AMD-SBE-β-CD inclusion complex in four different dissolution media was larger than that of the commercial product. The cumulative dissolution was more than 85% in water, pH 4.5 NaAc-HAC buffer, and pH 1.2 HCl aqueous solution. Moreover, the pharmacokinetic study found that the C max, AUC(0-t), and AUC(0-∞) of the AMI-SBE-β-CD inclusion complex had no significant difference in fasted and fed state, which indicated that the absorption of the AMI-SBE-β-CD inclusion complex in fasted state was increased and not affected by food.

  3. Synthesis and characterization of an amphiphilic cyclodextrin, a micelle with two recognition sites.

    PubMed

    Silva, O Fernando; Fernández, Mariana A; Pennie, Sarah L; Gil, Roberto R; de Rossi, Rita H

    2008-04-15

    A cyclodextrin derivative (Mod-CD) was synthesized through the monoesterification of beta-cyclodextrin (beta-CD) with 3-((E)-dec-2-enyl)-dihydrofuran-2,5-dione. The compound is an interesting surfactant that can form large aggregates not only through the interaction of the hydrophobic tails as in common amphiphilic compounds but also through the inclusion of the alkenyl chain into the cavity of another Mod-CD molecule. The self-inclusion of the chain in the cavity of cyclodextrin as well as the intermolecular inclusion was demonstrated by 1H NMR measurements that were able to detect methyl groups in three different environments. Besides, in the aggregates of Mod-CD, the cavity is available to interact with external guests such as phenolphthalein, 1-amino adamantane, and Prodan. Phenolphthalein has the same binding constant with Mod-CD and beta-CD, but the equilibrium constant for the interaction with Prodan is about 2 times larger for Mod-CD than for beta-CD. The latter result is attributed to the fact that this probe interacts with the micelle in two binding sites: the cavity of the cyclodextrin and the apolar heart of the micelle as evidenced by the spectrofluorimetric behavior of Prodan in solutions containing different concentrations of Mod-CD.

  4. 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.

  5. Temperature-controlled poly(propylene) glycol hydrophobicity on the formation of inclusion complexes with modified cyclodextrins. A DSC and ITC study.

    PubMed

    De Lisi, R; Lazzara, G; Milioto, S

    2011-07-21

    The study highlighted the main forces driving the formation of hydroxypropyl-cyclodextrins (HP-CDs) + poly(propylene) glycol 725 g mol(-1) inclusion complexes. The temperature parameter was chosen as the variable to modulate the hydrophobicity of the polymer, and consequently ITC experiments as functions of temperature as well as DSC measurements were done in a systematic way. The polymer is not included into HP-α-CD, it is strongly bound to HP-β-CD and it is floating in HP-γ-CD. The stability of the inclusion complexes is entropy controlled. The gain of the entropy is a unique result compared to the opposite literature findings for inclusion complexes based on polymers and CDs. This peculiarity is ascribable to the removal of water molecules from cages during complexation and this effect compensates the entropy loss due to constraints caused by the CD threading. In spite the host-guest van der Waals contacts are optimized, the enthalpies for the inclusion complex formation are positive and reveal the large heat required for dehydrating the propylene oxide units. All the macrocycles enhanced the polymer solubility in water. Increasing the affinity of the macrocycle to the macromolecule makes more expanded the one-phase area of the binodal curve. A new thermodynamic approach was proposed to predict quantitatively the binodal curve as well as the dependence of the enthalpy of separation phase on the macrocycle composition. The agreement between the experimental data and the computed values was excellent.

  6. Comprehensive investigation of hydroxypropyl methylcellulose, propylene glycol, polysorbate 80, and hydroxypropyl-beta-cyclodextrin for use in general toxicology studies.

    PubMed

    Thackaberry, Evan A; Kopytek, Stephen; Sherratt, Phillip; Trouba, Kevin; McIntyre, Barry

    2010-10-01

    This study was conducted to assess the safety and tolerability of the alternative formulation vehicles polysorbate 80 (PS80), propylene glycol (PG), and hydroxypropyl-beta-cyclodextrin (HPβCD) in general toxicology studies in the mouse, rat, dog, and monkey. Twenty (20) mg/kg of hydroxypropyl methylcellulose (MC, control), 10 mg/kg PS80, 1000 mg/kg PG, 500 mg/kg HPβCD, or 1000 mg/kg HPβCD were administered by oral gavage to mice, rats, dogs, and cynomolgus monkeys for approximately 90 days. The effects of these formulations on clinical observations, body weight and food consumption parameters, clinical pathology, and histopathology were evaluated across all species. The suitability of formulations containing up to 20 mg/kg MC, 10 mg/kg PS80, and 1000 mg/kg PG for use in preclinical safety studies was confirmed by a lack of effects on all parameters examined. However, formulations containing HPβCD produced elevated transaminase (aspartate and alanine aminotransferase) levels in rats and mice and fecal changes (loose and soft stool) in large animals. Although the etiology and toxicological significance of the transaminase elevations in rats and mice is uncertain, this finding could represent a significant liability for a preclinical formulation because of the critical importance of these biomarkers in the risk assessment of novel therapeutic agents. Based on these data, PS80 and PG are considered to be practical alternatives to MC in preclinical toxicology studies. However, formulations containing HPβCD should be used with caution because of the elevations in rodent transaminase levels.

  7. Effect of Tween80 and beta-cyclodextrin on the distribution of herbicide mefenacet in soil-water system.

    PubMed

    Guo, Huiqin; Zhang, Juan; Liu, Zhenyu; Yang, Shaogui; Sun, Cheng

    2010-05-15

    The effect of two solubilizers, Tween80 and beta-cyclodextrin (BCD) on the distribution of herbicide mefenacet (MF) in soil-water system was investigated. The results indicated that in the absence of Tween80 and BCD, the adsorption of MF on the natural soils fitted well with the Freundlich model and the K(f) values were positively related to organic carbon content in the soils. The K(oc) values were in the ranges of 52.7-606.6 L kg(-1). Desorption of MF from the soils was irreversible and positive hysteresis was observed in all the cases. In addition, it was found that the solubility of MF in aqueous phase could be enhanced greatly in the presence of Tween80 and BCD. The adsorption isotherms of Tween80 were fitted well with the linear Langmuir sorption model, and that of BCD fitted well with linear adsorption model. Moreover, it was also observed that the presence of proper concentration of Tween80 and BCD can enhance the transfer of MF from soil phase to aqueous phase. Although BCD presented more adsorption loss than Tween80, a carbon-normalized model suggested the adsorbed BCD had a weaker affinity for MF than the adsorbed Tween80, and experiment results showed the BCD could be a more effective solvent for desorption of MF compared with Tween80. The present study indicated that Tween80 and BCD had great potential in the area of ex situ enhanced soil remediation especially that based on full dynamic mixed model.

  8. Effects of randomly methylated-beta-cyclodextrins (RAMEB) on the bioavailability and aerobic biodegradation of polychlorinated biphenyls in three pristine soils spiked with a transformer oil.

    PubMed

    Fava, F; Ciccotosto, V F

    2002-03-01

    The low bioavailability of polychlorinated biphenyls (PCBs) in soils often results in their slow and partial aerobic biodegradation. The process can be enhanced by supplementing soils with cyclodextrins. However, pure cyclodextrins are expensive and we have therefore explored the use of a less costly technical grade mixture of randomly methylated-beta-cyclodextrins (RAMEB). RAMEB was tested at 0, 1, 3 and 5% (w/w) in the aerobic bioremediation and detoxification of a loamy-, a humic- and a sandy-soil, each artificially contaminated with a PCB-containing transformer oil (added PCBs: about 450 or 700 mg/kg), inoculated with an exogenous aerobic PCB-biodegrading bacterial co-culture and treated in slurry- and solid-phase laboratory conditions. Significant depletions of the spiked PCBs were observed in all microcosms of the three soils after 90 days of treatment; however, interesting yields of PCB dechlorination and detectable decreases of the original soil ecotoxicity were observed in the slurry-phase microcosms. RAMEB generally enhanced PCB-metabolism with effects which were dependent on the concentration at which it was applied, the physical-chemical nature of the amended soil, and the soil treatment conditions employed. RAMEB, which was slowly metabolized by soil microorganisms, enhanced the presence of PCBs and PCB-cometabolizing bacteria in the soil-water phase, suggesting that RAMEB enhances aerobic biodegradation of PCBs by increasing pollutant bioavailability in soil microcosms.

  9. [Enrichment of triphenyltin in water samples by beta-cyclodextrin cross-linking polymer and determination by hydride-generation atomic fluorescence spectrometry].

    PubMed

    Qiu, Hai-Ou; Yang, Xiao-Qiu; Yang, Ming; Xi, Yong-Qing; Tang, Zhi-Yong

    2007-04-01

    A new method was proposed for the enrichment of triphenyltin in water samples by beta-cyclodextrin cross-linking polymer and the quantitative determination of tin in triphenyltin by hydride-generation atomic fluorescence spectrometry. The chemical conditions and instrumental conditions were investigated and optimized. The method is sensitive and precise. The detection limit is 0.1 ng x mL(-1) and the RSD 2.64% (for 0.04 microg x mL(-1)). The proposed method has been successfully applied to the determination of triphenyltin in various water samples.

  10. Computer-aided molecular modeling techniques for predicting the stability of drug cyclodextrin inclusion complexes in aqueous solutions

    NASA Astrophysics Data System (ADS)

    Faucci, Maria Teresa; Melani, Fabrizio; Mura, Paola

    2002-06-01

    Molecular modeling was used to investigate factors influencing complex formation between cyclodextrins and guest molecules and predict their stability through a theoretical model based on the search for a correlation between experimental stability constants ( Ks) and some theoretical parameters describing complexation (docking energy, host-guest contact surfaces, intermolecular interaction fields) calculated from complex structures at a minimum conformational energy, obtained through stochastic methods based on molecular dynamic simulations. Naproxen, ibuprofen, ketoprofen and ibuproxam were used as model drug molecules. Multiple Regression Analysis allowed identification of the significant factors for the complex stability. A mathematical model ( r=0.897) related log Ks with complex docking energy and lipophilic molecular fields of cyclodextrin and drug.

  11. Enantioselective isolation of methyl jasmonate using permethyl-beta-cyclodextrin HPLC.

    PubMed

    Blanch, Gracia Patricia; Flores, Gema; Del Mar Caja, Maria; Ruiz Del Castillo, Maria Luisa

    2009-01-01

    A method based on the use of HPLC for the enantioselective resolution of the four stereoisomers of methyl jasmonate (MJ) with no need for the previous formation of the diastereoisomers is developed. To that end, a Nucleodex-beta-PM column as well as an optimization process considering different flow rates and mobile phase compositions were required. As a result, 0.8 mL/min and 55:45 methanol/water composition were the conditions selected to carry out the separation of the stereoisomers. Isolation of pure (-)- and (+)-MJ was accomplished by collecting the HPLC fractions corresponding to their elution time. SPE was subsequently used to concentrate and change the solvent of the HPLC fractions collected. Chiral GC and polarimetry were additionally employed to evaluate the purity and optical rotation, respectively, of the enantiomers separated. The results found in this study are particularly relevant considering that MJ stereoisomers are not commercially available.

  12. Analyses of polycyclic aromatic hydrocarbon (PAH) and chiral-PAH analogues-methyl-β-cyclodextrin guest-host inclusion complexes by fluorescence spectrophotometry and multivariate regression analysis.

    PubMed

    Greene, LaVana; Elzey, Brianda; Franklin, Mariah; Fakayode, Sayo O

    2017-03-05

    The negative health impact of polycyclic aromatic hydrocarbons (PAHs) and differences in pharmacological activity of enantiomers of chiral molecules in humans highlights the need for analysis of PAHs and their chiral analogue molecules in humans. Herein, the first use of cyclodextrin guest-host inclusion complexation, fluorescence spectrophotometry, and chemometric approach to PAH (anthracene) and chiral-PAH analogue derivatives (1-(9-anthryl)-2,2,2-triflouroethanol (TFE)) analyses are reported. The binding constants (Kb), stoichiometry (n), and thermodynamic properties (Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS)) of anthracene and enantiomers of TFE-methyl-β-cyclodextrin (Me-β-CD) guest-host complexes were also determined. Chemometric partial-least-square (PLS) regression analysis of emission spectra data of Me-β-CD-guest-host inclusion complexes was used for the determination of anthracene and TFE enantiomer concentrations in Me-β-CD-guest-host inclusion complex samples. The values of calculated Kb and negative ΔG suggest the thermodynamic favorability of anthracene-Me-β-CD and enantiomeric of TFE-Me-β-CD inclusion complexation reactions. However, anthracene-Me-β-CD and enantiomer TFE-Me-β-CD inclusion complexations showed notable differences in the binding affinity behaviors and thermodynamic properties. The PLS regression analysis resulted in square-correlation-coefficients of 0.997530 or better and a low LOD of 3.81×10(-7)M for anthracene and 3.48×10(-8)M for TFE enantiomers at physiological conditions. Most importantly, PLS regression accurately determined the anthracene and TFE enantiomer concentrations with an average low error of 2.31% for anthracene, 4.44% for R-TFE and 3.60% for S-TFE. The results of the study are highly significant because of its high sensitivity and accuracy for analysis of PAH and chiral PAH analogue derivatives without the need of an expensive chiral column, enantiomeric resolution, or use of a polarized

  13. Analyses of polycyclic aromatic hydrocarbon (PAH) and chiral-PAH analogues-methyl-β-cyclodextrin guest-host inclusion complexes by fluorescence spectrophotometry and multivariate regression analysis

    NASA Astrophysics Data System (ADS)

    Greene, LaVana; Elzey, Brianda; Franklin, Mariah; Fakayode, Sayo O.

    2017-03-01

    The negative health impact of polycyclic aromatic hydrocarbons (PAHs) and differences in pharmacological activity of enantiomers of chiral molecules in humans highlights the need for analysis of PAHs and their chiral analogue molecules in humans. Herein, the first use of cyclodextrin guest-host inclusion complexation, fluorescence spectrophotometry, and chemometric approach to PAH (anthracene) and chiral-PAH analogue derivatives (1-(9-anthryl)-2,2,2-triflouroethanol (TFE)) analyses are reported. The binding constants (Kb), stoichiometry (n), and thermodynamic properties (Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS)) of anthracene and enantiomers of TFE-methyl-β-cyclodextrin (Me-β-CD) guest-host complexes were also determined. Chemometric partial-least-square (PLS) regression analysis of emission spectra data of Me-β-CD-guest-host inclusion complexes was used for the determination of anthracene and TFE enantiomer concentrations in Me-β-CD-guest-host inclusion complex samples. The values of calculated Kb and negative ΔG suggest the thermodynamic favorability of anthracene-Me-β-CD and enantiomeric of TFE-Me-β-CD inclusion complexation reactions. However, anthracene-Me-β-CD and enantiomer TFE-Me-β-CD inclusion complexations showed notable differences in the binding affinity behaviors and thermodynamic properties. The PLS regression analysis resulted in square-correlation-coefficients of 0.997530 or better and a low LOD of 3.81 × 10- 7 M for anthracene and 3.48 × 10- 8 M for TFE enantiomers at physiological conditions. Most importantly, PLS regression accurately determined the anthracene and TFE enantiomer concentrations with an average low error of 2.31% for anthracene, 4.44% for R-TFE and 3.60% for S-TFE. The results of the study are highly significant because of its high sensitivity and accuracy for analysis of PAH and chiral PAH analogue derivatives without the need of an expensive chiral column, enantiomeric resolution, or use of a

  14. 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.

  15. 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

    2012-10-09

    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.

  16. 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.

  17. 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.

  18. Preliminary in vitro evaluation of genistein chemopreventive capacity as a result of esterification and cyclodextrin encapsulation.

    PubMed

    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.

  19. 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

  20. 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.

  1. 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).

  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

    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.

  3. 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.

  4. Separation of planar chiral ferrocene derivatives on beta-cyclodextrin-based polymer supports prepared via ring-opening metathesis graft-polymerization.

    PubMed

    Mayr, Betina; Schottenberger, Herwig; Elsnerb, Olaf; Buchmeiser, Michael R

    2002-10-11

    A series of beta-cyclodextrin (beta-CD) based chiral stationary phases (CSPs) were synthesized by ring-opening metathesis graft polymerization of various norborn-2-ene (NBE) substituted CDs. Chiral selectors based on endo/exo-6-O-(norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD, tris(endo/exo-6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD, tetrakis(endolexo-6-0-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD, hexakis(endo/exo-6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD and tetrakis(endo-6-O-norborn-2-ene-5-carboxyl)-beta-CD were grafted onto Nucleosil 300-5 using well-established grafting procedures. CSPs were investigated for their separation capabilities for a series of the planar chiral ferrocene derivatives, rac-ferroceno[2,3a]inden-1-one (1a, 1b), rac-6-(3-hydroxy-3-methylbut-1-yn-1-yl)ferroceno[2,3a]inden-1-one (2a, 2b), rac-ferrocene[2,3a]indene (3a, 3b), rac-endo 1-methoxy-1-allylferroceno[2,3a]indene (4a, 4b) and rac-1,4-dihydroxybutylferrocene (5a, 5b). Compounds la, lb and 2a, 2b bearing a carbonyl group were successfully separated on these CSPs, while compounds 3-5 do not undergo enantioselective interaction under the conditions applied. General aspects of separation as well as mechanistic implementations are discussed.

  5. Proparacaine complexation with beta-cyclodextrin and p-sulfonic acid calix[6]arene, as evaluated by varied (1)H-NMR approaches.

    PubMed

    Arantes, Lucas Micquéias; Scarelli, Camilla; Marsaioli, Anita Jocelyne; de Paula, Eneida; Fernandes, Sergio Antonio

    2009-09-01

    This study focused on the use of NMR techniques as a tool for the investigation of complex formation between proparacaine and cyclodextrins (CDs) or p-sulfonic acid calix[6]arene. The pH dependence of the complexation of proparacaine with beta-CD and p-sulfonic acid calix[6]arene was studied and binding constants were determined by (1)H NMR spectroscopy [diffusion-ordered spectroscopy (DOSY)] for the charged and uncharged forms of the local anesthetic in beta-CD and p-sulfonic acid calix[6]arene. The stoichiometries of the complexes was determined and rotating frame Overhauser enhancement spectroscopy (ROESY) 1D experiments revealed details of the molecular insertion of proparacaine into the beta-CD and p-sulfonic acid calix[6]arene cavities. The results unambiguously demonstrate that pH is an important factor for the development of supramolecular architectures based on beta-CD and p-sulfonic acid calix[6]arene as the host molecules. Such host-guest complexes were investigated in view of their potential use as new therapeutic formulations, designed to increase the bioavailability and/or to decrease the systemic toxicity of proparacaine in anesthesia procedures.

  6. [Analysis of seven compounds in mainstream cigarette smoke by ultra performance liquid chromatography using a beta-cyclodextrin mobile phase additive].

    PubMed

    Li, Zhonghao; Tang, Gangling; Pang, Yongqiang; Jiang, Xingyi; Chen, Zaigen; Hu, Qingyuan

    2010-08-01

    A rapid method for the analysis of hydroquinone, resorcinol, catechol, phenol, p-cresol, m-cresol, and o-cresol in mainstream cigarette smoke by ultra performance liquid chromatography (UPLC) using a beta-cyclodextrin (beta-CD) mobile phase additive was developed. The seven major phenolic compounds in mainstream smoke were collected with YC/T 255-2008 standard method. The extract was filtrated with 0.22 microm filtration film and then subjected to UPLC analysis. The separation was performed on an ACQUITY UPLC BEH Shield RP18 column, and the mobile phase with 4 g/L beta-CD additive was used. The fluorescence detection condition was optimized. The analysis time was 10 mm for one sample. Comparing with the high performance liquid chromatography (HPLC) methods published, the p-cresol and m-cresol were completely separated. In addition, the effect of beta-CD on fluorescence enhancement for seven major phenolic compounds was significant. The linearity were good between the peak area and the concentration in the linear ranges of seven phenolic compounds, and the correlation coefficients were greater than 0.999 9. The limits of detection of the method were 4 - 14 ng/cig, and the recoveries were 95.5% - 103.5% with relative standard deviations (RSDs) less than 4%.

  7. In situ electroactive and antioxidant supramolecular hydrogel based on cyclodextrin/copolymer inclusion for tissue engineering repair.

    PubMed

    Cui, Haitao; Cui, Liguo; Zhang, Peibiao; Huang, Yubin; Wei, Yen; Chen, Xuesi

    2014-03-01

    The injectable electroactive and antioxidant hydrogels are prepared from mixing the tetraaniline functional copolymers and α-cyclodextrin (α-CD) aqueous solution. UV-vis and CV of the copolymer solution showed good electroactive properties. The antioxidant ability of the copolymer is also proved. The gelation mechanism and properties of the system are studied by WAXD, DSC, and rheometer. The encapsulated cells are highly viable in the hydrogels, suggesting that the hydrogels have excellent cytocompatibility. After subcutaneous injection, H&E staining study suggests acceptable biocompatibility of the materials in vivo. Moreover, data shows the injectable electroactive material can effectively accelerate the proliferation of encapsulated cells with electrical stimuli, and the mechanism is also elaborated. Such an injectable electroactive hydrogel would more closely mimic the native extracellular matrix, thereby combining a biomimetic environment of long-term cell survival and electrical signal to support the generation of functional tissue.

  8. 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

  9. Effect of hydroxypropyl-beta-cyclodextrin on the solubility, stability and in-vitro release of ciprofloxacin for ocular drug delivery.

    PubMed

    Bozkir, Asuman; Denli, Zeynep Fusun; Basaran, Berrin

    2012-01-01

    Eye drops in the form of an aqueous solution with a lower viscosity are preferred for local administrations in ophthalmology. In ophthalmic formulations, cyclodextrins (CDs) are frequently used in recent years in order to increase water solubility, stability and bioavailability of an active substance and decrease an irritation to the eye. The scope of the present study was to investigate the influence of hydroxypropyl-beta-cyclodextrin (HPCD) on the solubility, stability and in vitro release of ciprofloxacin (CIP). According to the phase solubility studies, A(L) type solubility curve was obtained. HPCD improved the solubility of CIP 3 times at pH 5.5 and 2 times at pH 7.4. The two month stability studies indicated that CIP was more stable at pH 5.5 than at pH 7.4 and the stability of CIP was significantly increased by HPCD. The stability constant of the HPCD:CIP complex was increased further by a-ddition of 0.1% (w/v) polymer (HPMC and PVP) to the aqueous medium including HPCD. Stability constant of solutions prepared in an ultrasonic water bath was higher than solutions prepared by heating in an autoclave. The results indicated that the CIP:HPCD complex increased in vitro release of CIP and the addition of polymer promoted this increase even more.

  10. Influence of cyclodextrins on the proliferation of HaCaT keratinocytes in vitro.

    PubMed

    Hipler, U C; Schönfelder, U; Hipler, C; Elsner, P

    2007-10-01

    Safety and efficacy of pharmaceutical agents can be greatly improved by encapsulation within, or covalent attachment to, a biomaterial carrier. Drug delivery systems must deliver the necessary amount of drug to the targeted site for a necessary period of time, both efficiently and precisely. Various kinds of high-performance biomaterials are being constantly developed for this purpose. Cyclodextrins are potential candidates for such a role, because of their ability to alter physical, chemical, and biological properties of guest molecules through the formation of inclusion complexes. The alpha-, beta-, and gamma-cyclodextrins are widely used natural cyclodextrins, consisting of six, seven, and eight D-glucopyranose residues, respectively, linked by -1,4 glycosidic bonds into a macro cycle. Each cyclodextrin has its own ability to form inclusion complexes with specific guests, an ability, which depends on a proper fit of the guest molecule into the hydrophobic cyclodextrin cavity. The most common pharmaceutical application of cyclodextrins is to enhance the solubility, stability, and bioavailability of drug molecules. Such kinds of ligand-receptor complexes can be used for different applications, e.g., for a transdermal therapeutic system (TTS) or in biofunctional textiles. The aim of this study was the investigation of the influence of the different cyclodextrins on the cell proliferation using HaCaT keratinocytes as an in vitro test system. Moreover, the study was performed to find harmless and nontoxic cyclodextrin concentrations for dermal applications. By means of different independent in vitro tests could be confirmed that alpha-, beta-, and gamma-cyclodextrins in concentrations up to 0.1% (w/v) do not show any antiproliferative influence on HaCaT keratinocytes. Sometimes even proliferative effects could be found. However, all used cyclodextrins (besides gamma-cyclodextrin and its derivatives) in concentrations of 0.5 and 1% (w/v), respectively, exert a

  11. The encapsulation of β-lapachone in 2-hydroxypropyl-β-cyclodextrin inclusion complex into liposomes: a physicochemical evaluation and molecular modeling approach.

    PubMed

    Cavalcanti, Isabella M F; Mendonça, Elisângela A M; Lira, Mariane C B; Honrato, Sara B; Camara, Celso A; Amorim, Rosa V S; Mendes Filho, Josué; Rabello, Marcelo M; Hernandes, Marcelo Z; Ayala, Alejandro P; Santos-Magalhães, Nereide S

    2011-10-09

    The aim of this study was to encapsulate lapachone (β-lap) or inclusion complex (β-lap:HPβ-CD) in liposomes and to evaluate their physicochemical characteristics. In addition, the investigation of the main aspects of the interaction between β-lap and 2-hydroxypropyl-β-cyclodextrin (HPβ-CD), using both experimental and molecular modeling approaches was discussed. Furthermore, the in vitro drug release kinetics was evaluated. First, a phase solubility study of β-lap in HPβ-CD was performed and the β-lap:HPβ-CD was prepared by the freeze-drying technique. A 302-fold increase of solubility was achieved for β-lap in HPβ-CD solution with a constant of association K(1:1) of 961 M(-1) and a complexation efficiency of β-lap of 0.1538. (1)H NMR, TG, DSC, IR, Raman and SEM indicated a change in the molecular environment of β-lap in the inclusion complex. Molecular modeling confirms these results suggesting that β-lap was included in the cavity of HPβ-CD, with an intermolecular interaction energy of -23.67 kJ mol(-1). β-lap:HPβ-CD and β-lap-loaded liposomes presented encapsulation efficiencies of 93% and 97%, respectively. The kinetic rate constants of 183.95±1.82 μg/h and 216.25±2.34 μg/h were calculated for β-lap and β-lap:HPβ-CD-loaded liposomes, respectively. In conclusion, molecular modeling elucidates the formation of the inclusion complex, stabilized through hydrogen bonds, and the encapsulation of β-lap and β-lap:HPβ-CD into liposomes could provide an alternative means leading eventually to its use in cancer research.

  12. Solid dispersion of hydroxypropyl beta-cyclodextrin and ketorolac: enhancement of in-vitro dissolution rates, improvement in anti-inflammatory activity and reduction in ulcerogenicity in rats.

    PubMed

    Nagarsenker, M S; Meshram, R N; Ramprakash, G

    2000-08-01

    Ketorolac, is a non-steroidal anti-inflammatory drug, with strong analgesic activity. It is practically insoluble in water and has been implicated in causing gastrointestinal ulceration. This study describes the formulation of solid dispersions of ketorolac using hydroxypropyl beta-cyclodextrin (HPbeta-CyD) and beta-cyclodextin (beta-CyD) as carriers, to improve the aqueous solubility of the drug, thus enhancing its bioavailability. Also, reduction in ulcerogenicity was anticipated. Differential scanning calorimetry and X-ray diffraction studies indicated loss of crystalline nature of the drug, in the dispersions prepared with HPbeta-CyD. NMR studies revealed a strong interaction between drug and HPbeta-CyD. Solid dispersions of drug with beta-CyD retained the crystalline nature of the drug. All the solid dispersions showed a remarkable improvement in the rate and extent of dissolution of ketorolac. The kneaded dispersion with HPbeta-CyD prepared using a 1:1 alcohol-water mixture showed promise in reducing the ulcer-inducing effect of ketorolac in rats. Oral administration of this dispersion was found to inhibit carrageenan-induced paw oedema in rats to a significantly greater extent compared with ketorolac or its trometamol salt. Though beta-CyD as a carrier for ketorolac gave faster release of the poorly soluble drug, HPbeta-CyD proved to be superior to beta-CyD, as a carrier in the kneaded dispersion prepared using 1:1 alcohol-water mixture. These results suggest that solid dispersions of ketorolac with HPbeta-CyD aid in faster dissolution and better bioavailability of the drug. The higher solubility of the drug in the presence of HPbeta-CyD also reduces local gastrointestinal side-effects of the drug.

  13. Inclusion complexation of isoprenaline and methyl dopa with α- and β-cyclodextrin nanocavities: Spectral and theoretical study

    NASA Astrophysics Data System (ADS)

    Rajendiran, N.; Thulasidhasan, J.; Saravanan, J.

    2014-03-01

    Inclusion complex formation of isoprenaline (ISOP) and methyldopa (MDOP) with α-CD and β-CD were investigated. Solid inclusion complex nanomaterials were characterized by SEM, TEM, FTIR, DSC, 1H NMR and XRD methods. Spectral results showed that single emission (monomer) noticed in aqueous solution where as dual emission (excimer) in CD. Both drugs formed 1:2 (CD-drug2) inclusion complexes with CDs. Time-resolved fluorescence studies show that single exponential decay observed in water whereas biexponential decay observed in CD. Nano-sized particles were found in ISOP/CD while vesicles were obtained in MDOP/CD complexes. DSC results revealed that the thermal stability of drugs was improved when it was included in the CD nanocavity. Based on PM3 calculations, the inclusion structure of ISOP/CD and MDOP/CD complexes were proposed. Thermodynamic parameters and binding affinity of complexation of CD were determined by PM3 method.

  14. Factors Affecting the Formation of 2:1 Host:Guest Inclusion Complexes of 2-[(R-Phenyl)amine]-1,4-naphthalenediones (PAN) in β- and γ-Cyclodextrins.

    PubMed

    Jankowski, Christopher K; Lamouroux, Christine; Jiménez-Estrada, Manuel; Arseneau, Sebastien; Wagner, Brian D

    2016-11-18

    The molecular hosts cyclodextrins form inclusion complexes with a wide variety of guests, resulting in complexes with various host:guest stoichiometries. In the case of a series of 19 1,4-naphthoquinolines as guests with either β- or γ-cyclodextrin studied using electrospray mass spectroscopy, in most cases only 1:1 complexes were observed, with 2:1 host:guest complexes observed in just 6 out of 38 host:guest combinations. It is shown that these higher-order complexes were observed only in the case of small (or no) electronically withdrawing substituents, and were much less likely in the case of the larger γ-cyclodextrin host. The size and electronic properties of the substituents involved shows that both steric and electronic factors must be taken into account in predicting which cyclodextrin host:guest stoichiometries will be stable enough to form (or once formed, be robust enough to be observed in the ESI-MS experiments). It is clear that the prediction of host-guest stoichiometry for a specific host-guest pair is complicated, and involves a subtle interplay of both electronic and steric factors. However, there are definite trends, which can be used to help predict host:guest stoichiometry for a given host-guest pair.

  15. Interaction of iodine with 2-hydroxypropyl-alpha-cyclodextrin and its bactericidal activity.

    PubMed

    Tomono, K; Goto, H; Suzuki, T; Ueda, H; Nagai, T; Watanabe, J

    2002-11-01

    To obtain an effective iodine solution, the use of 2-hydroxypropyl-alpha-cyclodextrin (2-HP-alpha-CD) as solubilizer was examined in comparison with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), potassium iodide (KI), and polyvinylpyrrolidone (PVP). The stability constants for inclusion of iodine with cyclodextrin and KI were ascertained by the solubility method. The apparent stability constants increased in the following order: KI < beta-CD < alpha-CD < 2-HP-alpha-CD. This order was nearly in accordance with that of the stabilization ability. The largest volatile depression effect was exhibited by 2HP-alpha-CD. The measurement of the minimum inhibitory concentration (MC) using Escherichia coli NIH-J-2 and Staphylococcus aureus FDA209P suggested that the bactericidal activity of the iodine/2-HP-alpha-CD system was the same as that of the iodine/alpha-CD, iodine/beta-CD, and iodine/PVP systems. The present results suggest that the combination of 2-HP-alpha-CD and iodine is useful for a stable and effective iodine solution.

  16. Insights on novel particulate self-assembled drug delivery beads based on partial inclusion complexes between triglycerides and cyclodextrins.

    PubMed

    Aburahma, Mona Hassan

    2016-09-01

    Most of the newly designed drug molecules are lipophilic in nature and often encounter erratic absorption and low bioavailability after oral administration. Finding ways to enhance the absorption and bioavailability of these lipophilic drugs is one of the major challenges that face pharmaceutical industry nowadays. In view of that, the purpose of this review is to shed some light on a novel particulate self-assembling system named "beads" than can act as a safe carrier for delivering lipophilic drugs. The beads are prepared simply by mixing oils with cyclodextrin (CD) aqueous solution in mild conditions. A unique interaction between oil components and CD molecules occurs to form in situ surface-active complexes which are prerequisites for beads formation. This review mainly focuses on the fundamentals of beads preparation through reviewing present, yet scarce, literature. The key methods used for beads characterization are discussed in details. Also, the potential mechanisms by which beads increase the bioavailability of lipophilic drugs are illustrated. Finally, the related research areas that needs to be addressed in future for optimizing this promising delivery system are briefly outlined.

  17. 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

  18. Encapsulation of plai oil/2-hydroxypropyl-β-cyclodextrin inclusion complexes in polyvinylpyrrolidone (PVP) electrospun nanofibers for topical application.

    PubMed

    Tonglairoum, Prasopchai; Chuchote, Tudduo; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Opanasopit, Praneet

    2014-06-01

    The aim of this study was to prepare electrospun polyvinylpyrrolidone (PVP)/2-hydroxypropyl-β-cyclodextrin (HPβCD) nanofiber mats and to incorporate plai oil (Zingiber Cassumunar Roxb.). The plai oil with 10, 20 and 30% wt to polymer were incorporated in the PVP/HPβCD solution and electrospun to obtain nanofibers. The morphology and structure of the PVP and PVP/HPβCD nanofiber mats with and without the plai oil were analyzed using scanning electron microscopy (SEM). The thermal behaviors of the nanofiber mats were characterized using differential scanning calorimeter (DSC). Terpinen-4-ol was used as a marker of the plai oil. The amount of plai oil remaining in the PVP/HPβCD nanofiber mats was determined using gas chromatography-mass spectoscopy (GC-MS). The SEM images revealed that all of the fibers were smooth. The average diameter of fibers was 212-450 nm, and decreased with the increasing of plai oil content. The release characteristics of plai oil from the fiber showed the fast release followed by a sustained release over the experimental time of 24 h. The release rate ranged was in the order of 10% > 20% ∼ 30% plai oil within 24 h. Electrospun fibers with 20% plai oil loading provided the controlled release and also showed the highest plai oil content. Hence, this electrospun nanofiber has a potential for use as an alternative topical application.

  19. [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.

  20. Inclusion of Ethyl Acetoacetate Bearing 7-Hydroxycoumarin Dye by β-Cyclodextrin and its Cooperative Assembly with Mercury(II) Ions: Spectroscopic and Molecular Modeling Studies.

    PubMed

    Aliaga, Margarita E; Fierro, Angélica; Uribe, Iván; García-Río, Luis; Cañete, Álvaro

    2016-10-18

    The inclusion of the fluorescent organic dye, ethyl 3-(7-hydroxy-2-oxo-2H-chromen-3-yl)-3-oxopropanoate (1) by the host β-cyclodextrin (β-CD), and its response toward mercuric ions (Hg(2+) ), was studied by UV/Vis, fluorescence, and (1) H NMR spectroscopic analyses, mass spectrometry and molecular modeling studies. (1) H NMR measurements together with molecular modeling studies for dye 1 demonstrate that it exhibits two tautomeric forms (keto and enol); however, when the dye is included into the β-CD cavity, the enol form predominates. Moreover, by using spectroscopic and spectrometry techniques, a 1:1 stoichiometry was determined for the complexes formed between dye 1 (enol form) and β-CD, with a binding constant (Kb1 =1.8×10(4)  m(-1) ) and for the dye 1 (keto form)-Hg(2+) (Kb2 =2.3×10(3)  m(-1) ). Interestingly, in the presence of 1-β-CD complex and mercuric ions, a ternary supramolecular system (Hg-1-β-CD complex) was established, with a 1:1:1 stoichiometry and a Kb3 value of 4.3×10(3)  m(-1) , with the keto form of the dye being the only one present in this assembly. The three-component system provides a starting point for the development of novel and directed supramolecular assemblies.

  1. 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.

  2. Physicochemical characterization and analgesic effect of inclusion complexes of essential oil from Hyptis pectinata L. Poit leaves with β-cyclodextrin.

    PubMed

    Menezes, Paula dos P; Araujo, Adriano A de S; Doria, Grace Anne A; Quintans-Junior, Lucindo J; de Oliveira, Makson G B; dos Santos, Marcio R V; de Oliveira, Juliana F; Matos, Jivaldo do R; Carvalho, Flavio M de S; Alves, Pericles B; de Matos, Iara L; dos Santos, Darlisson A; Marreto, Ricardo N; da Silva, Gabriel F; Serafini, Mairim R

    2015-01-01

    The formation of inclusion complexes of Hyptis pectinata essential oil (EOHP), with potent activities such as anti-nociceptive, anti-inflammatory, among others, with β -cyclodextrin (β-CD), was obtained by slurry (SC) and paste procedures (PC). The gas chromatography coupled to the mass spectrometry (GC/MS) analysis demonstrated a total of 36.4% monoterpenes and 63.6% sesquiterpenes in the EOHP. The major components of EOHP were identified as (E)- caryophyllene (54.07%). The analysis of samples (PM, PC and SC) by GC/MS involved the surface and the total extracted oils. The GC/MS results suggested important differences between in SC and PC methods indicating the complexation of mono and sesquiterpenoids in different ratios. Furthermore, the thermal analysis techniques suggests the complexation, especially in SC, which show a thermogravimetry/derivative thermogravimetry (TG/DTG) peak at 140-270ºC, probably related to oil loss. Scanning electron microscopy (SEM) images showed reduction size of the samples mainly in the SC product. Additionally, EOHP/ β-CD improves pharmacological profile of EOHP alone in formalin-induced pain protocol in mice.

  3. β-Caryophyllene/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Improves Cognitive Deficits in Rats with Vascular Dementia through the Cannabinoid Receptor Type 2 -Mediated Pathway

    PubMed Central

    Lou, Jie; Teng, Zhipeng; Zhang, Liangke; Yang, Jiadan; Ma, Lianju; Wang, Fang; Tian, Xiaocui; An, Ruidi; Yang, Mei; Zhang, Qian; Xu, Lu; Dong, Zhi

    2017-01-01

    This work was conducted to prepare β-caryophyllene-hydroxypropyl-β-cyclodextrin inclusion complex (HPβCD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats. First, HPβCD/BCP was prepared, optimized, characterized, and evaluated. HPβCD/BCP and AM630 were then administered to VD rats to upregulate and downregulate the cannabinoid receptor type 2 (CB2). Results showed that HPβCD/BCP can significantly increase the bioavailability of BCP. Through the Morris water maze test, HPβCD/BCP can attenuate learning and memory deficits in rats. Cerebral blood flow (CBF) monitoring results indicated that HPβCD/BCP can promote the recovery of CBF. Moreover, molecular biology experiments showed that HPβCD/BCP can increase the expression levels of CB2 in brain tissues, particularly the hippocampus and white matter tissues, as well as the expression levels of PI3K and Akt. Overall, the findings demonstrated the protective effects of HPβCD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HPβCD/BCP in the therapy of vascular dementia in the future. PMID:28154534

  4. 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.

  5. Core-shell nanofibers of curcumin/cyclodextrin inclusion complex and polylactic acid: Enhanced water solubility and slow release of curcumin.

    PubMed

    Aytac, Zeynep; Uyar, Tamer

    2017-02-25

    Core-shell nanofibers were designed via electrospinning using inclusion complex (IC) of model hydrophobic drug (curcumin, CUR) with cyclodextrin (CD) in the core and polymer (polylactic acid, PLA) in the shell (cCUR/HPβCD-IC-sPLA-NF). CD-IC of CUR and HPβCD was formed at 1:2 molar ratio. The successful formation of core-shell nanofibers was revealed by TEM and CLSM images. cCUR/HPβCD-IC-sPLA-NF released CUR slowly but much more in total than PLA-CUR-NF at pH 1 and pH 7.4 due to the restriction of CUR in the core of nanofibers and solubility improvement shown in phase solubility diagram, respectively. Improved antioxidant activity of cCUR/HPβCD-IC-sPLA-NF in methanol:water (1:1) is related with the solubility enhancement achieved in water based system. The slow reaction of cCUR/HPβCD-IC-sPLA-NF in methanol is associated with the shell inhibiting the quick release of CUR. On the other hand, cCUR/HPβCD-IC-sPLA-NF exhibited slightly higher rate of antioxidant activity than PLA-CUR-NF in methanol:water (1:1) owing to the enhanced solubility. To conclude, slow release of CUR was achieved by core-shell nanofiber structure and inclusion complexation of CUR with HPβCD provides high solubility. Briefly, electrospinning of core-shell nanofibers with CD-IC core could offer slow release of drugs as well as solubility enhancement for hydrophobic drugs.

  6. 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

  7. 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.

  8. Synthesis, characterization and application of epichlorohydrin-β-cyclodextrin polymer.

    PubMed

    Gidwani, Bina; Vyas, Amber

    2014-02-01

    Cyclodextrins, the macrocyclic compounds are renowned for their inclusion ability. Several chemical and polymerized derivatives of parent cyclodextrins are synthesized to improve the physicochemical/biopharmaceutical properties of drug and inclusion capacity of cyclodextrin. This review article recapitulates the potential aspects of polymerized water-soluble derivative of β-cyclodextrin viz. epichlorohydrin-β-cyclodextrin polymer in different areas of drug delivery. Polymerized cyclodextrin combines the advantage of the properties of polymer (high molecular weight and higher solubility) with the formation of inclusion complex with cyclodextrin. This justifies the superiority of polymerized cyclodextrin over parent cyclodextrin and some other chemically modified and non-polymerized derivatives. The use of polymerized cyclodextrin in various fields like biomedical, pharmaceutical and gene delivery is increasing day-by-day. β-Cyclodextrin-epichlorohydrin polymer is a high molecular weight compound, which acts as an effective drug carrier for enhancing the solubility and oral bioavailability of drugs along with the increase in therapeutic efficiency. The future panorama of polymerized cyclodextrins is quite bright as they can serve as useful multifunctional tools for pharmaceutical scientists to develop and optimize drug delivery through various routes. Also, no information concerning the regulatory status and toxicity of polymerized cyclodextrins is available. So, there is a need to focus on these critical issues for resolving the problems associated with the development and commercialization of drug products.

  9. Encapsulation of quercetin and myricetin in cyclodextrins at acidic pH.

    PubMed

    Lucas-Abellán, Carmen; Fortea, Isabel; Gabaldón, José Antonio; Núñez-Delicado, Estrella

    2008-01-09

    The in vitro formation of quercetin- and myricetin-cyclodextrin inclusion complexes in acidic medium has been characterized using the enzymatic system horseradish peroxidase, which oxidizes those flavonols in the presence of H2O2. The presence of cyclodextrins (CDs) in the reaction medium inhibited flavonol oxidation due to the complexation of the flavonol in the hydrophobic cavity of CDs. This inhibitory effect depends on the complexation constant Kc between flavonol and the CD type used. The Kc for quercetin and myricetin with the different types of CD used was calculated by nonlinear regression of the inhibition curves obtained in the presence of CDs. In both cases (quercetin and myricetin), the Kc values obtained followed the order hydroxypropyl-beta-CDs > maltosyl-beta-CDs > beta-CDs, reflecting the greater affinity of modified cyclodextrins for the studied flavonols compared with their parental beta-CDs. Moreover, the complexation efficiency (CE) values for HP-beta-CDs and quercetin or myricetin were calculated (267.4 and 5.3, respectively), indicating that HP-beta-CDs are more efficient for the complexation of quercetin than myricetin in the studied conditions, despite of the K c values being very similar in both cases.

  10. Comparative studies of the artificial chaperone-assisted refolding of thermally denatured bovine carbonic anhydrase using different capturing ionic detergents and beta-cyclodextrin.

    PubMed

    Yazdanparast, Razieh; Khodarahmi, Reza; Soori, Effat

    2005-05-15

    Artificial chaperone-assisted refolding has been shown to be an effective approach for improving the refolding yield of some of the denatured proteins. Since identical concentrations of various detergents do not induce similar variations in the protein structures, we arranged to evaluate the artificial chaperoning capabilities of several ionic detergents as a function of charge, structure, and the hydrophobic tail length of the detergent. Our results indicate that carbonic anhydrase can be refolded from its denatured state via artificial chaperone strategy using both anionic and cationic detergents. However, the extent of refolding assistance (kinetic and refolding yield) were different due to protein and detergent net charges, detergent concentrations, and the length of hydrophobic portion of each detergent. These observed differences were attributed to physical properties of CA-detergent complexes and/or to the kinetics of detergent stripping by beta-cyclodextrin from the protein-detergent complexes which is apparently dependent on the detergent-beta-CD association constants and the nature of the partially stripped complexes.

  11. 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

  12. Effect of n-alkyl chain length on the complexation of phenanthrene and 9-alkyl-phenanthrene with $beta;-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Rima, J.; Aoun, E.; Hanna, K.

    2004-06-01

    The characteristics of host-guest complexation between β-cyclodextrin (β-CD) and phenanthrene derivatives (phenanthrene, n-propyl, n-butyl and n-hexyl-phenanthrene) were investigated by fluorescence spectrometry. Linear and non-linear regression methods were used to estimate the formation constants ( K1). A 1:1 stoichiometric ratio and an effect of n-alkyl chain length on the formation constant were observed for the binary inclusion complex between guest and β-CD. The formation constant dramatically increases with the length of n-alkyl, it starts from the value of 140 l mol -1 for the phenanthrene to reach the value of 580 l mol -1 for hexyl-phenanthrene. The effect of the temperature on the fluorescence intensity of each complex (guest-host) was also studied; and then the thermodynamic parameters were calculated. The main inclusion site seems to be aromatic moiety for short chain molecules, and it moves toward the alkyl chain part, as the chain becomes longer.

  13. Comparative assessment of effectiveness of ketoprofen and ketoprofen/beta-cyclodextrin complex in two experimental models of inflammation in rats.

    PubMed

    Grecu, Mariana; Năstasă, Valentin; Ilie, Cornelia; Miron, Liviu; Mareş, Mihai

    2014-01-01

    Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse effects such as gastrointestinal distress. The complexation of different groups of active substances with β-cyclodextrin (β-CD) has drawn considerable interest over recent years. The purpose of this study was to analyze the ketoprofen/β-cyclodextrin (K/β-CD) conjugate complex as well as to assess its anti-inflammatory effect after oral administration (doses of 30 mg/m(2) and 15 mg/m(2) of body surface), compared with ketoprofen. The studies were done on two models of experimentally-induced acute inflammation in rats (n = 48, 6/group), by means of intraplantar administration of a 10% aqueous kaolin suspension and intraperitoneal administration of a 1% sodium thioglycolate solution. The dynamics of the acute inflammatory process and the anti-inflammatory effects were monitored using plethysmometric determinations after 3, 6, 9, 12, 24 and 48 h (plantar inflammation), and the absorbance of the exudates (spectrophotometrically read) and nucleated cell counts after 24 h (peritoneal inflammation). The coupling of ketoprofen with β-CD resulted in increased solubility (100% in 60 min) of the newly-formed product, which further resulted in a higher bioavailability compared with ketoprofen (<40% in 120 min). In both models of experimentally-induced inflammation, the K/β-CD complex had a higher anti-inflammatory activity than ketoprofen.

  14. 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…

  15. Production and purification of refolded recombinant Plasmodium falciparum beta-ketoacyl-ACP reductase from inclusion bodies.

    PubMed

    Karmodiya, Krishanpal; Srivastav, Ratnesh Kumar; Surolia, Namita

    2005-07-01

    A recombinant form of Plasmodium falciparum beta-ketoacyl-ACP reductase (PfFabG) was overexpressed in Escherichia coli BL-21 codon plus (DE3). The resulting insoluble inclusion bodies were separated from cellular debris by extensive washing with buffer containing 0.05% Tween 20 and solubilized by homogenization with 8 M urea. Attempts to refold PfFabG from solubilized inclusion bodies employing Rotofor (separation based on different pIs of proteins in a mixture) followed by Ni(2+) or cation exchange chromatography were not successful either by bringing down the urea concentration instantaneously, stepwise, or by dialysis. Denatured PfFabG was therefore initially purified by cation exchange chromatography and was then correctly refolded at a final concentration of 100-200 microg/ml in a 20 mM Na-acetate buffer, pH 5.3, with 300 mM NaCl, 10% glycerol, and 0.05% Tween 20. The protein was found to be properly folded only in the presence of the cofactor NADPH and salt at a concentration 300 mM by drop dilution method at 2-8 degrees C for 12 h. The purified final product was >98% pure by denaturing gel electrophoresis. The purified protein was biologically active in a standard enzymatic assay using acetoacetyl-CoA as a substrate. The enzyme was found to be stable up to fourth day of purification and glycerol was found to stabilize enzyme activity for several weeks, during storage. This effort paves the way for elucidation of the structure-function correlations for PfFabG as well as exploration of the enzyme for developing inhibitors against it for combating malaria.

  16. Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

    PubMed Central

    Cruickshank, Dyanne L; Rougier, Natalia M; Vico, Raquel V; Bourne, Susan A

    2013-01-01

    Summary An anhydrous 1:1 crystalline inclusion complex between the organophosphorus insecticide fenitrothion [O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate] and the host compound heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) was prepared and its structure elucidated by single-crystal X-ray diffraction. This revealed two independent host molecules in the asymmetric unit. In one of these, the cavity is occupied by two disordered guest components (distinguishable as rotamers with respect to the P–OAr bond) while in the other, three distinct guest components with site-occupancies 0.44, 0.29 and 0.27 appear, the last having a reversed orientation relative to all the other components. Kinetic studies of the alkaline hydrolysis of fenitrothion in the presence of DIMEB showed a remarkable reduction of 84% in the rate of this reaction relative to that for the free substrate, a value exceeding those previously attained with the native hosts, β- and γ-cyclodextrin, and fully methylated β-cyclodextrin. PMID:23400042

  17. Application of a beta-cyclodextrin sulfate-immobilized precolumn to selective on-line enrichment and separation of heparin-binding proteins by column-switching high-performance liquid chromatography.

    PubMed

    Ishimura, K; Fukunaga, K; Irie, T; Uekama, K; Ohta, T; Nakamura, H

    1997-05-09

    A column-switching high-performance liquid chromatography (HPLC) system which consisted of a beta-cyclodextrin (beta-CD) sulfate-immobilized hydrophilic vinyl-polymer gel precolumn and a reversed-phase analytical column was developed for the selective on-line enrichment and separation of heparin-binding proteins. Of 15 proteins investigated, 10 proteins having heparin-binding activity were retained on the beta-CD sulfate precolumn almost quantitatively, in contrast 5 proteins having no heparin-binding activity were not retained. Calibration graphs for basic fibroblast growth factor constructed at various sample volumes were nearly identical, indicating that the protein could be enriched by this system. The system was successfully used for the selective separation of lysozyme in egg white. The beta-CD sulfate-immobilized precolumn showed no loss of analytical performance over 2 years during which about 400 samples were analysed.

  18. 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.

  19. Methyl-beta-cyclodextrin but not retinoic acid reduces EAAT3-mediated glutamate uptake and increases GTRAP3-18 expression.

    PubMed

    Butchbach, Matthew E R; Guo, Hong; Lin, Chien-liang Glenn

    2003-02-01

    The Na+-dependent glutamate transporter EAAT3 facilitates glutamate uptake into neurons as well as many other cell types. GTRAP3-18 (JWA, Arl6ip5) is a novel protein that interacts with EAAT3 and negatively modulates EAAT3-mediated glutamate uptake. Previous studies suggest that retinoic acid (RA) decreases Na+-dependent glutamate uptake and increases GTRAP3-18 protein expression. However, the RA used in those studies was complexed with methyl-beta-cyclodextrin (MebetaCD). In the present study we found that MebetaCD, but not RA, significantly reduced Na+-dependent EAAT3-mediated [3H]glutamate uptake in human embryonic kidney 293 (HEK293) cells. MebetaCD also significantly increased GTRAP3-18 protein expression in HEK293 cells as well as in rat hypothalamic neuron cultures. Intracerebroventricular administration of MebetaCD to the mouse brain resulted in a significant increase in GTRAP3-18 immunoreactivity in the hippocampus and cerebral cortex. In conclusion, we have shown that MebetaCD reduces EAAT3-mediated glutamate uptake and induces the expression of GTRAP3-18 protein.

  20. The enantioselective determination of chlorpheniramine and its major metabolites in human plasma using chiral chromatography on a beta-cyclodextrin chiral stationary phase and mass spectrometric detection.

    PubMed

    Fried, Karen M; Young, Andrea E; Usdin Yasuda, Sally; Wainer, Irving W

    2002-01-15

    A sensitive enantioselective high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of plasma concentrations of (-)(R)- and (+)(S)-chlorpheniramine (CP) and their metabolites, desmethyl-chlorpheniramine (DCP), didesmethyl-chorpheniramine (DDCP) and chlorpheniramine N-oxide (CPNO). Enantioselective separations were achieved on a beta-cyclodextrin chiral stationary phase (CYCLOBOND I 2000) with a mobile phase consisting of diethylamine acetate (0.25%, pH 4.4):methanol:acetonitrile [85:7.5:7.5, (v/v/v)]and a flow-rate of 0.5 ml/min. For CP, the enantioselectivity (alpha) of the separation was 1.12 with a resolution factor (R(s)) of 1.17. The method was validated for CP by using mass spectroscopy detection (MSD). Concentrations of each enantiomer could be measured down to 125 pg/ml from a 1-ml plasma sample. Extracted calibration curves were linear from 0.13 to 50.00 ng/ml for each enantiomer. The method was applied to samples from two clinical studies.

  1. A glycine ruthenium trithiacyclononane complex and its molecular encapsulation using cyclodextrins.

    PubMed

    Marques, Joana; Santos, Teresa M; Marques, Maria Paula; Braga, Susana S

    2009-11-28

    The complex Ru([9]aneS(3))(gly)Cl (gly = glycine) was obtained from the reaction of the precursor Ru([9]aneS(3))dmsoCl(2) with glycine and encapsulated into native beta-CD, a hydroxypropylated derivative HPbetaCD, and the methylated cyclodextrins TRIMEB and CRYSMEB. All four inclusion compounds were obtained with a 1:1 host:guest stoichiometry and characterised in the solid-state by powder X-ray diffraction, thermogravimetric analysis (TGA), and (13)C{(1)H} CP/MAS NMR and FTIR spectroscopies. The cytostatic and antiproliferative activity of the complex Ru([9]aneS(3))(gly)Cl and its four CD inclusion compounds was tested on the human osteosarcoma MG-63 cell line and the results compared to the inhibitory effect exerted by the pure cyclodextrins.

  2. Enantioseparation of baclofen with highly sulfated beta-cyclodextrin by capillary electrophoresis with laser-induced fluorescence detection.

    PubMed

    Kavran-Belin, Gamze; Rudaz, Serge; Veuthey, Jean-Luc

    2005-11-01

    The enantioseparation of baclofen (4-amino-3-p-chlorophenylbutyric acid) was achieved by CE-LIF with highly sulfated beta-CD (HS-beta-CD) as chiral selector. Naphthalene-2,3-dicarboxaldehyde was used for the derivatization of nonfluorescent baclofen. HS-beta-CD (2%) containing 50 mM borate buffer at pH 9.5 was chosen as the optimal running electrolyte and applied to the analysis of baclofen enantiomers in human plasma. The linearity of calibration curves (R2 > or = 0.998) for R-(-) and S-(+)-baclofen was in the 0.1-2.0 microM concentration range. After a simple ACN-protein precipitation, the LOD of baclofen in plasma sample was found as low as 50 nM.

  3. Chiral recognition of macromolecules with cyclodextrins: pH- and thermosensitive copolymers from N-isopropylacrylamide and N-acryloyl-D/L-phenylalanine and their inclusion complexes with cyclodextrins.

    PubMed

    Gingter, Sabrina; Bezdushna, Ella; Ritter, Helmut

    2011-02-14

    In the present work we report the enantioselective recognition of water soluble stimuli-responsive polymers bearing phenylalanine moieties via host-guest interaction with β-cyclodextrin and randomly-methylated-β-cyclodextrin (RAMEB-CD). We synthesised N-acryloyl-D/L-phenylalanine monomers (2(D), 2(L)) which were then copolymerised under free radical conditions with N-isopropylacrylamide (NIPAAm). The resulting copolymers 3(D) and 3(L) exhibit a lower critical solution temperature (LCST) of 25 °C. As a further benefit, the presence of a free carboxylic group in the copolymer system gives a high sensitivity to the pH value in respect to the LCST value. The enantioselective recognition of the side groups of copolymers 3(D) and 3(L) and their solubility behaviour were investigated by dynamic light scattering and 2D NMR spectroscopy, respectively.

  4. 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.

  5. Molecular Modeling and Physicochemical Properties of Supramolecular Complexes of Limonene with α- and β-Cyclodextrins.

    PubMed

    Dos Passos Menezes, Paula; Dos Santos, Polliana Barbosa Pereira; Dória, Grace Anne Azevedo; de Sousa, Bruna Maria Hipólito; Serafini, Mairim Russo; Nunes, Paula Santos; Quintans-Júnior, Lucindo José; de Matos, Iara Lisboa; Alves, Péricles Barreto; Bezerra, Daniel Pereira; Mendonça Júnior, Francisco Jaime Bezerra; da Silva, Gabriel Francisco; de Aquino, Thiago Mendonça; de Souza Bento, Edson; Scotti, Marcus Tullius; Scotti, Luciana; de Souza Araujo, Adriano Antunes

    2017-02-01

    This study evaluated three different methods for the formation of an inclusion complex between alpha- and beta-cyclodextrin (α- and β-CD) and limonene (LIM) with the goal of improving the physicochemical properties of limonene. The study samples were prepared through physical mixing (PM), paste complexation (PC), and slurry complexation (SC) methods in the molar ratio of 1:1 (cyclodextrin:limonene). The complexes prepared were evaluated with thermogravimetry/derivate thermogravimetry, infrared spectroscopy, X-ray diffraction, complexation efficiency through gas chromatography/mass spectrometry analyses, molecular modeling, and nuclear magnetic resonance. The results showed that the physical mixing procedure did not produce complexation, but the paste and slurry methods produced inclusion complexes, which demonstrated interactions outside of the cavity of the CDs. However, the paste obtained with β-cyclodextrin did not demonstrate complexation in the gas chromatographic technique because, after extraction, most of the limonene was either surface-adsorbed by β-cyclodextrin or volatilized during the procedure. We conclude that paste complexation and slurry complexation are effective and economic methods to improve the physicochemical character of limonene and could have important applications in pharmacological activities in terms of an increase in solubility.

  6. Folding and aggregation of TEM beta-lactamase: analogies with the formation of inclusion bodies in Escherichia coli.

    PubMed Central

    Georgiou, G.; Valax, P.; Ostermeier, M.; Horowitz, P. M.

    1994-01-01

    The enzyme TEM beta-lactamase has been used as a model for understanding the pathway leading to formation of inclusion bodies in Escherichia coli. The equilibrium denaturation of TEM beta-lactamase revealed that an intermediate that has lost enzymatic activity, native protein fluorescence, and UV absorption, but retains 60% of the native circular dichroism signal, becomes populated at intermediate (1.0-1.4 M) concentrations of guanidium chloride (GdmCl). This species exhibits a large increase in bis-1-anilino-8-naphthalene sulfonic acid fluorescence, indicating the presence of exposed hydrophobic surfaces. When TEM beta-lactamase was unfolded in different initial concentrations of GdmCl and refolded to the same final conditions by dialysis a distinct minimum in the yield of active protein was observed for initial concentrations of GdmCl in the 1.0-1.5 M range. It was shown that the lower reactivation yield was solely due to the formation of noncovalently linked aggregates. We propose that the aggregation of TEM beta-lactamase involves the association of a compact state having partially exposed hydrophobic surfaces. This hypothesis is consistent with our recent findings that TEM beta-lactamase inclusion bodies contains extensive secondary structure (Przybycien TM, Dunn JP, Valax P, Georgiou G, 1994, Protein Eng 7:131-136). Finally, we have also shown that protein aggregation was enhanced at higher temperatures and in the presence of 5 mM dithiothreitol and was inhibited by the addition of sucrose. These conditions exert a similar effect on the formation of inclusion bodies in vivo. PMID:7703842

  7. Comparative evaluation of the chiral recognition potential of single-isomer sulfated beta-cyclodextrin synthesis intermediates in non-aqueous capillary electrophoresis.

    PubMed

    Fejős, Ida; Varga, Erzsébet; Benkovics, Gábor; Darcsi, András; Malanga, Milo; Fenyvesi, Éva; Sohajda, Tamás; Szente, Lajos; Béni, Szabolcs

    2016-10-07

    The enantioselectivity of neutral single-isomer synthetic precursors of sulfated-β-cyclodextrins was studied. Four neutral single-isomer cyclodextrins substituted on the secondary side with acetyl and/or methyl functional groups, heptakis(2-O-methyl-3,6-dihydroxy)-β-cyclodextrin (HM-β-CD), heptakis(2,3-di-O-acetyl-6-hydroxy)-β-cyclodextrin (HDA-β-CD), heptakis(2,3-di-O-methyl-6-hydroxy)-β-cyclodextrin (HDM-β-CD), heptakis(2-O-methyl-3-O-acetyl-6-hydroxy)-β-cyclodextrin (HMA-β-CD), and their sulfated analogs the negatively charged heptakis(2,3-di-O-methyl-6-sulfato)-β-cyclodextrin (HDMS-β-CD) and heptakis(2,3-di-O-acetyl-6-sulfato)-β-cyclodextrin (HDAS-β-CD) were investigated by non-aqueous capillary electrophoresis in the view of enantiodiscrimination for various drugs and related pharmaceutical compounds. The focus of the present work was on the chiral selectivity studies of the neutral derivatives, which are the synthesis intermediates of the sulfated products. The chiral recognition experiments proved that among the neutral compounds the HMA-β-CD shows remarkable enantioselectivity towards chiral guests in non-aqueous capillary electrophoresis, while HM-β-CD, HDA-β-CD and HDM-β-CD failed to resolve any of the 25 studied racemates under the applied experimental conditions. In order to get deeper insight into the molecular interactions between the studied single-isomer cyclodextrin and chiral fluoroquinolones (ofloxacin, gatifloxacin and lomefloxacin) and β-blockers (propranolol), (1)H and ROESY NMR experiments were performed. The 2-O-methylation in combination with the 3-O-acetylation of the host was evidenced to exclusively carry the essential spatial arrangement for chiral recognition.

  8. Betamethasone-in-cyclodextrin-in-liposome: the effect of cyclodextrins on encapsulation efficiency and release kinetics.

    PubMed

    Piel, Géraldine; Piette, Marie; Barillaro, Valery; Castagne, Delphine; Evrard, Brigitte; Delattre, Luc

    2006-04-07

    Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. "Drugs-in-cyclodextrin-in-liposome" systems were previously proposed to overcome this drawback but studies were limited to betaCD and HPbetaCD. In some cases, other cyclodextrins may be more interesting than betaCD or HPbetaCD, such as methylated cyclodextrins. However, these cyclodextrins are known to extract lipid components from the lipid membrane, which may destabilize liposomes. We tested the influence of several cyclodextrins (betaCD, gammaCD, Dimeb, Trimeb, Crysmeb, Rameb, HPbetaCD and HPgammaCD) on the aqueous solubility of betamethasone by phase solubility diagrams and on the encapsulation efficiency in liposomes. The release kinetics of betamethasone was studied using Franz diffusion cells. We showed that release kinetics are directly correlated with encapsulation efficiency, which is closely related to betamethasone concentration in cyclodextrin complex solution. No liposome destruction was observed, even with the testing of methylated cyclodextrins at the highest concentration (40 mM). This can be explained by the fact that these cyclodextrins have a higher affinity for betamethasone than for cholesterol. This was proved by the comparison of phase solubility diagrams of both betamethasone and cholesterol.

  9. Release mechanisms of a sparingly water-soluble drug from controlled porosity-osmotic pump pellets using sulfobutylether-beta-cyclodextrin as both a solubilizing and osmotic agent.

    PubMed

    Sotthivirat, Sutthilug; Haslam, John L; Lee, Ping I; Rao, Venkatramana M; Stella, Valentino J

    2009-06-01

    The purpose of this work is to delineate the release mechanisms of a sparingly water-soluble drug, prednisolone (PDL), from a microporous or controlled porosity-osmotic pump pellet (CP-OPP) using sulfobutylether-beta-cyclodextrin (CD) as both a solubilizing and osmotic agent. All factors, osmotic and diffusional, influencing drug release as described by the Theeuwes and Zentner equation were partially demonstrated in an earlier paper1 and are further quantitatively evaluated here to determine whether the equation may be applied to CP-OPPs. The PDL release rate from the CP-OPPs containing precomplexed PDL follows the zero-order kinetics for up to 30-40% of drug release during the first 1-2 h and subsequently nonzero order kinetics. The zero-order drug release phase reveals the main contribution is from osmotic pumping with a negligible diffusion component, resulting from the nearly constant driving forces in the system. The nonzero order drug release phase is associated with the dynamic changes in the system (e.g., declining osmotic driving force and greater diffusion component with time). In addition, the parameters related to membrane characteristics were determined, and the effect of viscosity was evaluated for the pellet system. The membranes coated on the CP-OPPs are less permeable to water or solutes than the membranes coated on the previously reported tablets. The viscosity due to the CD decreases as a function of CD concentration, which partly affects the observed drug release profiles. The viscosity effect of CD is significant and captured in a hydraulic permeability term.

  10. Effect of methyl-beta-cyclodextrin treatment of pig spermatozoa on in vitro fertilization and embryo development in the absence or presence of caffeine.

    PubMed

    Mao, Jiude; Wu, Guang-Ming; Prather, Randy S; Smith, Michael F; Cantley, Tom; Rieke, August; Didion, Brad A; Day, Billy N

    2005-12-01

    A series of experiments were carried out to develop a new method to reduce pig polyspermic fertilization and produce more normal embryos, in vitro. Experiment 1 determined the effect of methyl-beta-cyclodextrin (MCD) treatment during cryopreservation on sperm acrosome reaction and sperm fertilization. Compared to the non-MCD-treated control, MCD treatment increased the percentage of acrosome-reacted spermatozoa at thawing and 2h after incubation in fertilization medium (P<0.01). Treatment with MCD also increased (P<0.05) sperm-penetration rate, number of spermatozoa in oocytes, and fertilization efficiency in the caffeine-free fertilization medium. Experiment 2 was designed to examine the effect of withdrawal of caffeine (caffeine-free) from fertilization medium on fertilization parameters and early embryo development. Using MCD-treated spermatozoa, there was no difference in sperm-penetration rate, oocyte cleavage rate, and blastocyst formation rate between the caffeine-free and caffeine-supplemented groups. However, polyspermic fertilization rate was lower, and fertilization efficiency and blastocyst cell number were higher in the caffeine-free group compared to the caffeine-supplemented group (P<0.05). Experiment 3 studied the effect of caffeine and different concentrations of spermatozoa on fertilization parameters. Sperm-penetration rate did not differ between the caffeine-free and the caffeine-supplemented groups at different sperm concentrations. Caffeine and sperm concentration had an effect on the number of spermatozoa in oocytes and on the polyspermic fertilization rate (P<0.002). Caffeine also affected fertilization efficiency (P<0.05). In conclusion, treating spermatozoa with MCD and withdrawing caffeine from fertilization medium may provide a new method to produce a large number of normal embryos, in vitro.

  11. 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.

  12. 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

  13. Adsorption of a dye on clay and sand. Use of cyclodextrins as solubility-enhancement agents.

    PubMed

    De Lisi, Rosario; Lazzara, Giuseppe; Milioto, Stefania; Muratore, Nicola

    2007-11-01

    Laboratory-scale studies were aimed at elucidating the physico-chemical aspects on the removal process of crystal violet (CV) from waters and solid substrates. The laponite clay (RD) and sand were chosen for the double aim at investigating them as CV adsorbents for water treatment and as substrates which mime the soil components. Sand is very effective in removing CV from waters. The cyclodextrins (CDs) were exploited as solubility-enhancement agents to remove CV from the solid substrates. They are powerful solvent media because they extract the CV from sand forming water-soluble CV/CD inclusion complexes and do not show affinity for sand. Optimum performance was shown by the modified CDs (i.e. hydroxypropyl-beta-cyclodextrin and methyl-beta-cyclodextrin). A linear correlation between the logarithm of the equilibrium constant for the CV/CD inclusion complexes formation (K(cpx)) and the maximum amount of CV extracted from sand in the columns experiments at a flow rate of 1.5 ml min(-1) was drawn. This relationship predicts that CDs with K(cpx)<180 M(-1) are not suitable for CV removal from sand. CDs failed to displace CV from RD because they generate the formation of RD clusters where CV remains entrapped.

  14. Unfolding story of inclusion-body myositis and myopathies: role of misfolded proteins, amyloid-beta, cholesterol, and aging.

    PubMed

    Askanas, Valerie; Engel, W King

    2003-03-01

    Sporadic inclusion-body myositis and hereditary inclusion-body myopathies are progressive muscle diseases leading to severe disability. We briefly summarize their clinical pictures and pathologic diagnostic criteria and discuss the latest advances in illuminating their pathogenic mechanism(s). We emphasize how different etiologies might lead to the strikingly similar pathology and possibly similar pathogenic cascade. On the basis of our research, several processes seem to be important in relation to the still speculative pathogenesis, including (a) increased transcription and accumulation of amyloid-beta precursor protein and accumulation of its proteolytic fragment amyloid-beta; (b) abnormal accumulation of components related to lipid metabolism, for example, cholesterol, accumulation of which is possibly owing to its abnormal trafficking; (c) oxidative stress; (d) accumulations of other Alzheimer's disease-related proteins; and (e) a milieu of muscle cellular aging in which these changes occur. We discuss a potentially very important role of unfolded and/or misfolded proteins as a possible mechanism in the formations of the inclusion bodies and other abnormalities.

  15. Comparative study of polymer containing beta-cyclodextrin and -COOH for adsorption toward aniline, 1-naphthylamine and methylene blue.

    PubMed

    Zhao, Dong; Zhao, Liang; Zhu, Cheng-Shen; Shen, Xiangyu; Zhang, Xiaozhuan; Sha, Baofeng

    2009-11-15

    Three different polymers P1, P2 and P3 (P1 containing both beta-CD and -COOH, P2 containing beta-CD and P3 containing -COOH) were synthesized and applied to adsorption toward aniline, 1-naphthylamine and methylene blue. The concentrations (C) before and after adsorption were determined and the adsorption capacities (q) of P1, P2 and P3 were calculated. The maximum adsorption capacities (q(max)) toward aniline: q(max) (P1)=104 micromol g(-1), q(max) (P2)=14.9 micromol g(-1) and q(max) (P3)=53.1 micromol g(-1); toward 1-naphthylamine: q(max) (P1)=184 micromol g(-1), q(max) (P2)=53.8 micromol g(-1) and q(max) (P3)=125 micromol g(-1); toward methylene blue: q(max) (P1)=200 micromol g(-1), q(max) (P2)=12.7 micromol g(-1) and q(max) (P3)=215 micromol g(-1). P1 exhibited remarkable adsorption toward all the three adsorbates. P2 was almost equal to P1 in adsorption toward methylene blue, but was less efficient than P1 in adsorption toward aniline and 1-naphthylamine. P3 also exhibited considerable adsorption toward aniline and 1-naphthylamine, but was inefficient toward methylene blue. P1 was obtained from nontoxic materials and through environment friendly procedures, so it was potentially an efficient and green adsorbent for water purification.

  16. Simultaneous determination of ampicillin, cefoperazone, and sulbactam in pharmaceutical formulations by HPLC with beta-cyclodextrin stationary phase.

    PubMed

    Tsou, Tai-Li; Huang, Yu-Chuan; Lee, Chiu-Wey; Lee, An-Rong; Wang, Hsian-Jenn; Chen, Su-Hwei

    2007-10-01

    An accurate and reproducible method for the simultaneous determination of ampicillin (AMP), sulbactam (SUL), and cefoperazone (CFP) in pharmaceutical formulations by using HPLC with beta-CD stationary phase was developed. It involved the use of the added tetraethylammonium acetate (TEAA) reagent, pH, and methanol as the significant parameters to find the optimum separation condition. A high resolution and selectivity of analytes was obtained by running the mobile phase in methanol-5 mM TEAA buffer = 35:65 (v/v, pH 4.5) at 280 nm. The mean recoveries ranged from 96.6 to 103.3% for AMP in the synthetic mixture, 97.6 to 103.0% for SUL, and 97.0 to 104.0% for CFP. The low LOD (<1.8 microg/mL) and low CV (<0.9%) assured that this method was sensitive and reproducible. The assay of analytes in commercial products exhibited that it was convenient and reproducible for routine analyses of these components in sterilized H(2)O, saline, or 5% dextrose injection solutions.

  17. Analytical and preparative enantioseparation of DL-penicillamine and DL-cysteine by high-performance liquid chromatography on alpha-acid glycoprotein and beta-cyclodextrin columns using ninhydrin as a reversible tagging reagent.

    PubMed

    Bhushan, Ravi; Kumar, Rajender

    2009-04-10

    Two sulfur-containing amino acids, DL-cysteine (Cys) and DL-penicillamine (PenA), were condensed with ninhydrin to form their spirothiazolidine derivatives. These were separated by HPLC using alpha-acid glycoprotein (AGP) and beta-cyclodextrin (beta-CD) columns. The resolution conditions were optimized and the results were compared. Since the method provided resolution greater than 2 it was also applied to preparative separation. After separation, each of them was detagged using Zn dust and 10% aqueous trifluoroacetic acid. For analytical purposes dinitrophenyl (DNP) derivatives of DL-Cys and DL-PenA were also prepared and were resolved on both the columns. The detection was carried out using photodiode array detection system at 231 nm. The limits of detection were found to be 0.01% and 0.004% for spirothiazolidine carboxylic acid and DNP derivatives, respectively.

  18. Cyclodextrin stabilised emulsions and cyclodextrinosomes.

    PubMed

    Mathapa, Baghali G; Paunov, Vesselin N

    2013-11-07

    We report the preparation of o/w emulsions stabilised by microcrystals of cyclodextrin-oil inclusion complexes. The inclusion complexes are formed by threading cyclodextrins from the aqueous phase on n-tetradecane or silicone oil molecules from the emulsion drop surface which grow further into microrods and microplatelets depending on the type of cyclodextrin (CD) used. These microcrystals remain attached on the surface of the emulsion drops and form densely packed layers which resemble Pickering emulsions. The novelty of this emulsion stabilisation mechanism is that molecularly dissolved cyclodextrin from the continuous aqueous phase is assembled into colloid particles directly onto the emulsion drop surface, i.e. molecular adsorption leads to effective Pickering stabilisation. The β-CD stabilised tetradecane-in-water emulsions were so stable that we used this system as a template for preparation of cyclodextrinosomes. These structures were produced solely through formation of cyclodextrin-oil inclusion complexes and their assembly into a crystalline phase on the drop surface retained its stability after the removal of the core oil. The structures of CD-stabilised tetradecane-in-water emulsions were characterised using optical microscopy, fluorescence microscopy, cross-polarised light microscopy and WETSEM while the cyclodextrinosomes were characterised by SEM. We also report the preparation of CD-stabilised emulsions with a range of other oils, including tricaprylin, silicone oil, isopropyl myristate and sunflower oil. We studied the effect of the salt concentration in the aqueous phase, the type of CD and the oil volume fraction on the type of emulsion formed. The CD-stabilised emulsions can be applied in a range of surfactant-free formulations with possible applications in cosmetics, home and personal care. Cyclodextrinosomes could find applications in pharmaceutical formulations as microencapsulation and drug delivery vehicles.

  19. Impact of different cultivation and induction regimes on the structure of cytosolic inclusion bodies of TEM1-beta-lactamase.

    PubMed

    Margreiter, Gerd; Schwanninger, Manfred; Bayer, Karl; Obinger, Christian

    2008-10-01

    The enzyme TEM1-beta-lactamase has been used as a model to study the impact of different cultivation and induction regimes on the structure of cytosolic inclusion bodies (IBs). The protein has been heterologously expressed in Escherichia coli in fed-batch cultivations at different temperatures (30, 37, and 40 degrees C) as well as induction regimes that guaranteed distinct product formation rates and ratios of soluble to aggregated protein. Additionally, shake flask cultivations at 20, 30, and 37 degrees C were performed. IBs were sampled during the whole bioprocess and structural analysis was performed by attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy. This work clearly demonstrates that the tested production regimes and rates had no impact on the IB structure, which was characterized by decreased alpha-helical and increased and modified beta-sheet contents compared to the native protein. Moreover, aggregates formed during refolding of IBs by solubilization and simple dilution showed very similar FT-IR spectra suggesting (i) the existence of only one critical folding step from which either aggregation (IB formation) or native folding branches off, and (ii) underlining the important role of the specific amino acid sequence in aggregation. The findings are discussed with respect to the known structure of TEM1-beta-lactamase and the reported kinetics of its (un)folding as well as contradictory data on the effect of cultivation regimes on IB structure(s) of other proteins.

  20. 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

  1. 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.

  2. Kaempferol complexation in cyclodextrins at basic pH.

    PubMed

    Mercader-Ros, María Teresa; Lucas-Abellán, Carmen; Gabaldón, José Antonio; Fortea, María Isabel; Martínez-Cachá, Adela; Núñez-Delicado, Estrella

    2010-04-28

    The complexation of kaempferol with cyclodextrins (CDs) (beta-, G(2)-beta-, and HP-beta-CDs) in basic medium was studied, and the complexation constants (K(c)) were calculated by using enzymatic, solubility, and fluorometric methods. This is the first time that a decrease in fluorescence has been observed as result of the analyte complexation by CDs. The highest K(c) value for kaempferol complexation was obtained for HP-beta-CDs. To establish the validity of the fluorometric method for determining the K(c) between kaempferol and CDs, the same parameters were also determined by enzymatic and solubility methods. The enzymatic method was carried out by using horseradish peroxidase as oxidative enzyme, and the K(c) values obtained were similar to those obtained by using the solubility method. However, the fluorometric method underestimated the K(c) value by about 1.2-fold with respect to the other methods used. In all cases HP-beta-CDs showed the highest K(c) value, indicating that they are more efficient in the formation of inclusion complexes with kaempferol.

  3. The interaction of caffeine with substituted cyclodextrins in water

    NASA Astrophysics Data System (ADS)

    Terekhova, I. V.; Kumeev, R. S.; Al'Per, G. A.

    2007-07-01

    The interaction of caffeine with hydroxypropyl-and methylcyclodextrins in water was studied by the calorimetry, spectroscopy, and solubility methods at 298.15 K. The interaction of caffeine with these cyclodextrins did not result in the formation of stable inclusion complexes and was mostly accompanied by predominantly endothermic effects of particle dehydration. The introduction of substituents and changes in the size of cyclodextrin molecular cavity did not influence the ability of cyclodextrins to form complexes with caffeine. The conclusion was drawn that substituted cyclodextrins could not be used for increasing the solubility of caffeine in water.

  4. Estimation of the poly (ε-caprolactone) [PCL] and α-cyclodextrin [α-CD] stoichiometric ratios in their inclusion complexes [ICs], and evaluation of porosity and fiber alignment in PCL nanofibers containing these ICs.

    PubMed

    Narayanan, Ganesh; Gupta, Bhupender S; Tonelli, Alan E

    2015-12-01

    This paper describes the utilization of Proton-Nuclear Magnetic Resonance spectroscopy ((1)H NMR) to quantify the stoichiometric ratios between poly (ε-caprolactone) [PCL] and α-cyclodextrin (α-CD) present in their non-stoichiometric inclusion complexes [(n-s)-ICs]. This paper further describes the porosity and fiber alignment of PCL nanofibers nucleated by the [(n-s)-ICs] during electrospinning. (1)H NMR indicated that the two non-stoichiometric inclusion complexes utilized in this study had differing stoichiometric ratios that were closely similar to those of the starting ratios used to make them. Studies on porosity and fiber alignments were conducted on the scanning electron microscope images using ImageJ. The data indicates that both fiber alignment as well as porosity values remain almost the same over all the samples. Thus we can conclude the improvement in mechanical properties was due only to the loading of the ICs, and their subsequent interaction with bulk unthreaded PCL.

  5. 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

  6. Cyclodextrin production and genetic characterization of cyclodextrin glucanotranferase of Paenibacillus graminis.

    PubMed

    Vollú, Renata Estebanez; da Mota, Fabio Faria; Gomes, Eliane Aparecida; Seldin, Lucy

    2008-05-01

    Paenibacillus graminis strains were described recently as cyclodextrin (CD) producers. Cyclodextrins are produced by cyclodextrin glucanotransferase (CGTase) which has not been characterized in P. graminis. Similar amounts of alpha- and beta-CDs were produced by P. graminis (MC22.13) and P. macerans (LMD24.10(T)). Primers were designed to sequence the gene encoding CGTase from P. graminis. A phylogenetic tree was constructed and P. graminis CGTase protein showed to be closer (79.4% protein identity) to P. macerans |P31835|. Hybridization studies suggested that the gene encoding CGTase is located in different positions in the genomes of P. macerans and P. graminis.

  7. Bilayer vesicles of amphiphilic cyclodextrins: host membranes that recognize guest molecules.

    PubMed

    Falvey, Patrick; Lim, Choon Woo; Darcy, Raphael; Revermann, Tobias; Karst, Uwe; Giesbers, Marcel; Marcelis, Antonius T M; Lazar, Adina; Coleman, Anthony W; Reinhoudt, David N; Ravoo, Bart Jan

    2005-02-04

    A family of amphiphilic cyclodextrins (6, 7) has been prepared through 6-S-alkylation (alkyl=n-dodecyl and n-hexadecyl) of the primary side and 2-O-PEGylation of the secondary side of alpha-, beta-, and gamma-cyclodextrins (PEG=poly(ethylene glycol)). These cyclodextrins form nonionic bilayer vesicles in aqueous solution. The bilayer vesicles were characterized by transmission electron microscopy, dynamic light scattering, dye encapsulation, and capillary electrophoresis. The molecular packing of the amphiphilic cyclodextrins was investigated by using small-angle X-ray diffraction of bilayers deposited on glass and pressure-area isotherms obtained from Langmuir monolayers on the air-water interface. The bilayer thickness is dependent on the chain length, whereas the average molecular surface area scales with the cyclodextrin ring size. The alkyl chains of the cyclodextrins in the bilayer are deeply interdigitated. Molecular recognition of a hydrophobic anion (adamantane carboxylate) by the cyclodextrin vesicles was investigated by using capillary electrophoresis, thereby exploiting the increase in electrophoretic mobility that occurs when the hydrophobic anions bind to the nonionic cyclodextrin vesicles. It was found that in spite of the presence of oligo(ethylene glycol) substituents, the beta-cyclodextrin vesicles retain their characteristic affinity for adamantane carboxylate (association constant K(a)=7.1 x 10(3) M(-1)), whereas gamma-cyclodextrin vesicles have less affinity (K(a)=3.2 x 10(3) M(-1)), and alpha-cyclodextrin or non-cyclodextrin, nonionic vesicles have very little affinity (K(a) approximately 100 M(-1)). Specific binding of the adamantane carboxylate to beta-cyclodextrin vesicles was also evident in competition experiments with beta-cyclodextrin in solution. Hence, the cyclodextrin vesicles can function as host bilayer membranes that recognize small guest molecules by specific noncovalent interaction.

  8. Enhancement of orofacial antinociceptive effect of carvacrol, a monoterpene present in oregano and thyme oils, by β-cyclodextrin inclusion complex in mice.

    PubMed

    Silva, Juliane C; Almeida, Jackson R G S; Quintans, Jullyana S S; Gopalsamy, Rajiv Gandhi; Shanmugam, Saravanan; Serafini, Mairim Russo; Oliveira, Maria R C; Silva, Bruno A F; Martins, Anita O B P B; Castro, Fyama F; Menezes, Irwin R A; Coutinho, Henrique D M; Oliveira, Rita C M; Thangaraj, Parimelazhagan; Araújo, Adriano A S; Quintans-Júnior, Lucindo J

    2016-12-01

    Orofacial pain is associated with diagnosis of chronic pain of head, face, mouth, neck and all the intraoral structures. Carvacrol, a naturally occurring isoprenoid with diverse class of biological activities including anti-inflammatory, analgesic, antitumor and antioxidant properties. Now, the antinociceptive effect was studied in mice pretreatment with carvacrol (CARV) and β-cyclodextrin complex containing carvacrol (CARV-βCD) in formalin-, capsaicin-, and glutamate- induced orofacial nociception. Mice were pretreated with vehicle (0.9% Nacl, p.o.), CARV (10 and 20mg/kg, p.o.), CARV-βCD (10 and 20mg/kg, p.o.) or MOR (10mg/kg, i.p.) before the nociceptive behavior induced by subcutaneous injections (s.c.) of formalin (20μl, 2%), capsaicin (20μl, 2.5μg) or glutamate (20μl, 25μM) into the upper lip respectively. The interference on motor coordination was determined using rotarod and grip strength meter apparatus. CARV-βCD reduced the nociceptive during the two phases of the formalin test, whereas CARV did not produced the reduction in face-rubbing behavior in the initial phase. CARV-βCD (20mg/kg, p.o.) produced 49.3% behavior pain while CARV alone at 20mg/kg, p.o, produced 28.7% of analgesic inhibition in the second phase of formalin test. CARV, CARV-βCD and Morphine (MOR) showed a significant reduction against nociception caused by capsaicin or glutamate injection. Thus the encapsulation of carvacrol in β-cyclodextrin can acts as a considerable therapeutic agent with pharmacological interest for the orofacial pain management.

  9. 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

  10. Comparison of chiral recognition capabilities of cyclodextrins for the separation of basic drugs in capillary zone electrophoresis.

    PubMed

    Jin, L J; Li, S F

    1998-04-24

    The enantiomeric separation of some racemic anti-histamines and anti-malarials, namely (+/-)-pheniramine, (+/-)-brompheniramine, (+/-)-chlorpheniramine, (+/-)-doxylamine, and (+/-)-chloroquine, was investigated by capillary zone electrophoresis. The enantiomeric separation of five compounds was obtained by addition of approximately 7 mM (1%, w/v) sulfated-beta-cyclodextrin into the buffer as a chiral selector. The effects of sulfated-beta-cyclodextrin concentration and buffer pH on migration and resolution are discussed. Two other cyclodextrins, carboxyethylated-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin were also investigated. Four of the racemic compounds were resolved using 14 mM (2%, w/v) carboxyethylated-beta-cyclodextrin while 28 mM (4%, w/v) hydroxypropyl-beta-cyclodextrin resolved only two of them. It was found that the type of substituent and the degree of substitution on the rim of the CD structure played an important role in enhancing the chiral recognition. Cyclodextrins with negatively charged substituents and higher degree of substitution on the rim of the structure proved to give better resolution to the cationic racemic compounds compared with cyclodextrin with neutral substituents. This is due to the countercurrent mobility of the negatively charged cyclodextrin relative to the cationic analytes thus allowing for a smaller difference in interaction constants to achieve a successful resolution of enantiomers. Furthermore, lower concentrations of negatively charged cyclodextrins were necessary to achieve the equivalent resolutions as compared with the neutral ones.

  11. (L)- or (D)-valine tert-butylamide grafted on permethylated beta-cyclodextrin derivatives as new mixed binary chiral selectors: versatile tools for capillary gas chromatographic enantioseparation.

    PubMed

    Stephany, O; Dron, F; Tisse, S; Martinez, A; Nuzillard, J-M; Peulon-Agasse, V; Cardinaël, P; Bouillon, J-P

    2009-05-01

    This work deals with the synthesis of two mixed binary chiral selectors prepared by grafting (L)- or (D)-valine tert-butylamide on permethylated cyclodextrin macrocycle. The enantioselective properties of the new chiral selectors diluted in OV11 polysiloxane (35% phenyl- and 65% methylsiloxane) were investigated by means of injections of 117 racemic mixtures. The mixed chiral selectors with (L)-valine and, to a lesser extent with (D)-valine, were found to have an improved enantioselectivity toward amino acid derivatives by comparison to permethylated cyclodextrin. The enantioseparation capability of these new chiral selectors has proven to be slightly less efficient than Chirasil-L-Val (Alltech) for amino acid derivatives, but it has been extended to include terpenes, lactones, esters, aliphatic compounds and aryl alcohols.

  12. Rapid Transacylations of Activated Ester Substrates Bound to the Primary Side Beta-Cyclodextrin-Cyclen Conjugate and its M(2+) Complexes

    DTIC Science & Technology

    1990-02-20

    nitrophenolate from the following substrates: p- nitrophenyl acetate (8; "PNPA"), bis-p-nitrophenylcarbonate (9; "BIS-PNPC"), and p...afford accelerations in ester, amide, and phosphate hydrolyses, due in part to their ability to form metal-bound hydroxide under conditions that are...SECURITY CLASSIFICATION OF THIS PAGE p- nitrophenyl acetate. at pH 5.2. Subsequent descriptions of cyclodextrin-based artificial metalloenzymes have been

  13. AmyA, an alpha-amylase with beta-cyclodextrin-forming activity, and AmyB from the thermoalkaliphilic organism Anaerobranca gottschalkii: two alpha-amylases adapted to their different cellular localizations.

    PubMed

    Ballschmiter, Meike; Armbrecht, Martin; Ivanova, Krasimira; Antranikian, Garabed; Liebl, Wolfgang

    2005-07-01

    Two alpha-amylase genes from the thermophilic alkaliphile Anaerobranca gottschalkii were cloned, and the corresponding enzymes, AmyA and AmyB, were investigated after purification of the recombinant proteins. Based on their amino acid sequences, AmyA is proposed to be a lipoprotein with extracellular localization and thus is exposed to the alkaline milieu, while AmyB apparently represents a cytoplasmic enzyme. The amino acid sequences of both enzymes bear high similarity to those of GHF13 proteins. The different cellular localizations of AmyA and AmyB are reflected in their physicochemical properties. The alkaline pH optimum (pH 8), as well as the broad pH range, of AmyA activity (more than 50% activity between pH 6 and pH 9.5) mirrors the conditions that are encountered by an extracellular enzyme exposed to the medium of A. gottschalkii, which grows between pH 6 and pH 10.5. AmyB, on the other hand, has a narrow pH range with a slightly acidic pH optimum at 6 to 6.5, which is presumably close to the pH in the cytoplasm. Also, the intracellular AmyB is less tolerant of high temperatures than the extracellular AmyA. While AmyA has a half-life of 48 h at 70 degrees C, AmyB has a half-life of only about 10 min at that temperature, perhaps due to the lack of stabilizing constituents of the cytoplasm. AmyA and AmyB were very similar with respect to their substrate specificity profiles, clearly preferring amylose over amylopectin, pullulan, and glycogen. Both enzymes also hydrolyzed alpha-, beta-, and gamma-cyclodextrin. Very interestingly, AmyA, but not AmyB, displayed high transglycosylation activity on maltooligosaccharides and also had significant beta-cyclodextrin glycosyltransferase (CGTase) activity. CGTase activity has not been reported for typical alpha-amylases before. The mechanism of cyclodextrin formation by AmyA is unknown.

  14. 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.

  15. 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.

  16. Separation and characterization of humic acids from Antarctica by capillary electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Inclusion complexes of humic acids with cyclodextrins.

    PubMed

    Gajdosová, Dagmar; Novotná, Klára; Prosek, Pavel; Havel, Josef

    2003-10-03

    A new capillary electrophoresis procedure based on micellar electrokinetic capillary chromatography for the separation of humic acids (HAs) isolated from Antarctica soil was developed. The HAs were separated and characterized using a background electrolyte containing 0.09 M borate+0.09 M Tris+0.001 M EDTA (BTE) of pH 8.3, modified with alpha-, beta-, or gamma-cyclodextrins (CDs) and sodium dodecyl sulfate. It was found that from alkaline solution of HAs in the presence of CDs, the HAs are not completely precipitated with a strong acid and a certain part (some fractions) remains soluble. Mass spectrometry shows that HAs contain 15-25 simple low-Mr compounds and several families of compounds with similar structure (m/z approximately 800-1200). Comparison of HA analysis from Antarctica soil with those of soil HAs from the American continent show a high similarity between the samples and confirm several identical compounds and some with very similar structural units.

  17. Cyclodextrins inhibit replication of scrapie prion protein in cell culture.

    PubMed

    Prior, Marguerite; Lehmann, Sylvain; Sy, Man-Sun; Molloy, Brendan; McMahon, Hilary E M

    2007-10-01

    Prion diseases are fatal neurodegenerative disorders that are caused by the conversion of a normal host-encoded protein, PrP(C), to an abnormal, disease-causing form, PrP(Sc). This paper reports that cyclodextrins have the ability to reduce the pathogenic isoform of the prion protein PrP(Sc) to undetectable levels in scrapie-infected neuroblastoma cells. Beta-cyclodextrin removed PrP(Sc) from the cells at a concentration of 500 microM following 2 weeks of treatment. Structure activity studies revealed that antiprion activity was dependent on the size of the cyclodextrin. The half-maximal inhibitory concentration (IC(50)) for beta-cyclodextrin was 75 microM, whereas alpha-cyclodextrin, which possessed less antiprion activity, had an IC(50) of 750 microM. This report presents cyclodextrins as a new class of antiprion compound. For decades, the pharmaceutical industry has successfully used cyclodextrins for their complex-forming ability; this ability is due to the structural orientation of the glucopyranose units, which generate a hydrophobic cavity that can facilitate the encapsulation of hydrophobic moieties. Consequently, cyclodextrins could be ideal candidates for the treatment of prion diseases.

  18. [Amphiphilic cyclodextrins and their applications. Preparation of nanoparticles based on amphiphilic cyclodextrins for biomedical applications].

    PubMed

    Parrot-Lopez, H; Perret, F; Bertino-Ghera, B

    2010-01-01

    Solubilization of hydrophobic drugs at the molecular level as inclusion complexes inside cyclodextrins (CDs) offers a good alternative for improving their stability, solubility and bioavailability, and for preventing against their possible toxicity or controlling secondary effects. Therefore CDs are widely used as solubilizing excipients. However since dissociation takes place too readily upon dilution, inclusion complexes inside simple water-soluble CD appears ineffective for drug delivery applications. Chemical modifications of CDs allow them to self-organize as larger assemblies useful for resolving this lability issue. Depending on the position, the number and the nature of these groups, amphiphilic CDs can form assemblies such as vesicles, solid-lipid nanoparticles, nanospheres, liquid crystals, or micellar systems. This review deals with the synthesis of amphiphilic cyclodextrins leading to supramolecular assemblies and the physical properties of these assemblies. From the first sulfonated amphiphilic cyclodextrins isolated in our laboratory in 2003, to the latest ones being regioselectively functionalized by two or four fluoroalkyl chains, through the persubstituted fluorinated cyclodextrines, all these amphiphilic cyclodextrins have shown good abilities for encapsulation. Complexation of bioactive molecules (acyclovir) by these modified alpha-cyclodextrin derivatives, the encapsulation efficiency and release profile were measured as an assessment of the properties of such nanoparticles regarding drug delivery applications.

  19. Study of the inclusion complexes formed between cetirizine and α-, β-, and γ-cyclodextrin and evaluation on their taste-masking properties.

    PubMed

    Stojanov, Mladen; Wimmer, Reinhard; Larsen, Kim L

    2011-08-01

    Complexation properties of cetirizine dihydrochloride (cetirizine) with α-, β-, and γ-cyclodextrin (CD) were investigated by ultra violet (UV) and nuclear magnetic resonance (NMR) spectroscopies and isothermal titration calorimetry (ITC). The use of the continuous variation method, applied on UV and NMR data, demonstrated 1:1 complex stoichiometry for cetirizine-α-CD, cetirizine-β-CD, and cetirizine-γ-CD, respectively. NMR two-dimensional Rotational nuclear Overhauser Effect SpectroscopY experiments revealed that for α- and β-CD, the complexation takes place by including either the phenyl or chlorophenyl ring of the cetirizine into the CD cavity, whereas in the case of γ-CD, both rings can be included simultaneously. Association constants (K(a)) determined by UV spectroscopy demonstrated that cetirizine forms more stable complex with β-CD (K(a) = 5641 ± 358 M(-1)) than α-CD (K(a) = 1434 ± 60 M(-1)). No information could be extracted from the UV spectroscopic analysis of cetirizine-γ-CD solutions. ITC results for association constant determination were in compliance with UV results and confirmed that the highest association constant was found for the cetirizine-β-CD complex (2540 ± 122 M(-1)). The association constants from ITC measurements for cetirizine-γ-CD and cetirizine-α-CD complexes were found to be 1200 ± 50 and 800 ± 22 M(-1) , respectively. Taste-masking studies revealed that β-CD is the only native CD recommendable for oral pharmaceutical formulations.

  20. Derivatization, stabilization and detection of biogenic amines by cyclodextrin-modified capillary electrophoresis-laser-induced fluorescence detection.

    PubMed

    Male, K B; Luong, J H

    2001-08-17

    o-Phthalaldehyde (OPA) derivatives of eight biogenic amines were stabilized at 5 degrees C by forming inclusion complexes with methyl-beta-cyclodextrin (MBCD). The derivatives were separated and detected by cyclodextrin-modified capillary electrophoresis (CE) with UV or laser-induced fluorescence (LIF) detection. Using a borate buffer, pH 9.0 consisting of ethanol and a mixture of negatively charged sulfobutylether-beta-cyclodextrin and neutral MBCD, baseline separation of the eight OPA derivatives was achieved within 25 min with high separation efficiencies. The detection limits (S/N=3) obtained by UV and LIF detection were determined to be 10 microM and 0.250 microM, respectively. Glutamic acid was added after the initial derivatization step to neutralize residual OPA which otherwise caused a significant interference, particularly when analysis was performed around the detection limit of the OPA derivatives. Important biogenic amines in fish, wine and urine were then derivatized and determined by CE-LIF. In the case of sole and rainbow trout, the results obtained were validated by an enzymatic assay using putrescine oxidase.

  1. Insights into cyclodextrin interactions during sample stacking using capillary isotachophoresis with on-line microcoil NMR detection.

    PubMed

    Almeida, Valentino K; Larive, Cynthia K

    2005-09-01

    On-line capillary isotachophoresis (cITP)-NMR experiments were used to probe the interactions of the pharmaceutical compounds S-alprenolol, S-atenolol, R-propranolol, R-salbutamol and S-terbutaline with beta-cyclodextrin (beta-CD) during cITP concentration. In cITP, ionic analytes are concentrated and separated on the basis of their electrophoretic mobility. Because neutral molecules have an electrophoretic mobility of zero, they are normally not concentrated or separated in electrophoretic experiments like cITP. Most of the analytes studied were concentrated by cITP sample stacking by a factor of around 300. For analytes that formed a strong inclusion complex, beta-CD co-concentrated during cITP sample stacking. However, once the focusing process was complete, a discrete diffusional boundary formed between the cITP-focused analyte band and the leading and trailing electrolyte, which restricted diffusion into and out of the analyte band.

  2. New organic nanoporous polymers and their inclusion complexes

    SciTech Connect

    Ma, M.; Li, D.

    1999-04-01

    The authors have recently fabricated cyclodextrin polymers that exhibit an interconnected nanoporosity with a dramatically increased inclusion formation constant, K {ge} 10{sup 8} M{sup {minus}1}. This is significant because a simple conversion from cyclodextrin monomers to nanoporous polymers could have such a dramatic effect on noncovalent interactions in aqueous solutions. Previous studies on cyclodextrin polymers focus mostly on cross-linking cyclodextrin with epichlorohydrin which is commercially available and has low binding constant to organics. Studies using cyclodextrins to coat solid particles as a stationary phase for enantiomer separation were also reported. Formation of inclusion complexes are rarely proven in these cyclodextrin polymers, including using cholesterol as a template to synthesize cyclodextrin polymers.

  3. Formulation, characterization and evaluation of cyclodextrin-complexed bendamustine-encapsulated PLGA nanospheres for sustained delivery in cancer treatment.

    PubMed

    Gidwani, Bina; Vyas, Amber

    2016-03-01

    PLGA nanospheres are considered to be promising drug carrier in the treatment of cancer. Inclusion complex of bendamustine (BM) with epichlorohydrin beta cyclodextrin polymer was prepared by freeze-drying method. Phase solubility study revealed formation of AL type complex with stability constant (Ks = 645 M(-1)). This inclusion complex was encapsulated into PLGA nanospheres using solid-in-oil-in-water (S/O/W) technique. The particle size and zeta potential of PLGA nanospheres loaded with cyclodextrin-complexed BM were about 151.4 ± 2.53 nm and - 31.9 ± (-3.08) mV. In-vitro release study represented biphasic release pattern with 20% burst effect and sustained slow release. DSC studies indicated that inclusion complex incorporated in PLGA nanospheres was not in a crystalline state but existed in an amorphous or molecular state. The cytotoxicity experiment was studied in Z-138 cells and IC50 value was found to be 4.3 ± 0.11 µM. Cell viability studies revealed that the PLGA nanospheres loaded with complex exerts a more pronounced effect on the cancer cells as compared to the free drug. In conclusion, PLGA nanospheres loaded with inclusion complex of BM led to sustained drug delivery. The nanospheres were stable after 3 months of storage conditions with slight change in their particle size, zeta potential and entrapment efficiency.

  4. Complex permittivities of cyclomaltooligosaccharides (cyclodextrins) over microwave frequencies to 26 GHz.

    PubMed

    Atwater, J E

    2000-07-24

    Complex permittivities (epsilon*) for microwave radiation between 0.5 and 26 GHz have been determined for alpha-, beta-, and gamma-cyclodextrins in the solid state at room temperature. For the real component of epsilon*, maxima occur near 0.6 GHz, and the relation beta > alpha > gamma is evident across the full-frequency spectrum. Dielectric loss is significant only between 5 and 12 GHz for beta- and gamma-cyclodextrins with maxima near 7.5 GHz.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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

  10. The kinetics and molecular modeling of the complexation of tenoxicam with cyclodextrins in solution.

    PubMed

    Rawashdeh, Abdelmonem; Mizyed, Shehadeh; Mahmoud, Sabri; Marji, Deeb

    2008-11-15

    The effect of cyclodextrins on photodegradation of tenoxicam (TEN) was studied at pH 4, 7 and 10. After 60 min of irradiation with UV light, the photodegradation was extensive. All cyclodextrins (alpha, beta, or gamma) stabilize TEN and reduce the rate of photodegradation. The largest effect of cyclodextrins is at pH 7. Molecular modeling results help to explain and manipulate the results. The results are discussed and compared with other results from previous studies.

  11. 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.

  12. 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.

  13. Electrospray ionization mass spectrometry: a key analytical tool for the characterization of regioselectively derivatized maltooligosaccharides obtained starting from natural beta-cyclodextrin.

    PubMed

    Lesur, David; Gassama, Abdoulaye; Moreau, Vincent; Djedaïni-Pilard, Florence; Brique, Arnaud; Pilard, Serge

    2006-01-01

    The development of natural cyclodextrins (CDs) for various industrial applications (agroalimentary, cosmetic or pharmaceutical) constitutes a continuous challenge. For the integration of these agricultural plant products in the creation of super-absorbent biodegradable and hypoallergenic materials (water-retaining agents, cosmetic hydrating and texturing, pharmaceutical and horticultural products) to replace synthetic polymers, we have developed chemical methods to access regioselectively C-6-derivatized maltooligosaccharides starting from CDs. These compounds are highly suitable for further chemical modifications and are expected to give access to a new class of polymeric materials with potential applications such as water-retaining agents in the disposable nappies industry. For the structural analysis of carbohydrates, electrospray ionization mass spectrometry (ESI-MS) offers precise results, analytical versatility and very high sensitivity. We report herein the rapid and convenient follow-up of chemical reactions, the purity evaluation of intermediates and final products, and the structural characterization of derivatized maltooligosaccharides, obtained by acidic cleavage (acetolysis) of halogenated and esterified CDs, using ESI-MS in combination with the high-resolution (HRMS) and tandem mass spectrometry (MS/MS) capabilities of a quadrupole orthogonal time-of-flight (Q-TOF) mass spectrometer.

  14. A randomized, double-blind, placebo-controlled study to test the efficacy of topical 2-hydroxypropyl-Beta-cyclodextrin in the prophylaxis of recurrent herpes labialis.

    PubMed

    Senti, Gabriela; Iannaccone, Reto; Graf, Nicole; Felder, Manuela; Tay, Fabian; Kündig, Thomas

    2013-01-01

    Herpes labialis affects one third of the population. We evaluated the topical application of an antiviral compound, hydroxypropyl-β-cyclodextrin (2-HPβCD), in reducing herpes labialis relapses. In this double-blind, randomized, placebo-controlled trial, 40 patients were randomized to a polyethylene glycol (PEG) formulation containing 20% 2-HPβCD or to a vehicle control arm. The gel was applied to the lips twice daily for 6 months. The primary objective was reducing herpes relapses. Surprisingly, the drug group had significantly more relapses than the vehicle group (p = 0.003). While the median numbers of relapses in the preceding year were 12 in the vehicle group and 10 in the drug group, both groups experienced very few relapses during the 6-month treatment period, with a median of 0 in the vehicle group and a median of 2 in the drug group. The impressive reduction of relapses in both groups may be due to a placebo effect or due to the topical treatment with PEG.

  15. β-Cyclodextrin as the suitable molecular container for isopulegol enantiomers.

    PubMed

    Ceborska, Magdalena; Szwed, Kamila; Suwinska, Kinga

    2013-09-12

    Isopulegol, an insoluble in water and highly volatile compound, due to its neuroactive properties is a potentially important agent for medical applications. Formation of "host-guest" molecular complexes with cyclodextrins would lead to the increase of its water solubility and bioavailability. Interactions between native cyclodextrins (α, β and γ) and isopulegol enantiomers were studied in solution proving the formation of inclusion complexes for β- and γ-cyclodextrins. For the more stable complexes with β-cyclodextrin crystal structures were obtained showing the formation of molecular capsules forming molecular container able to accommodate two guest molecules.

  16. Phase solubility, 1H NMR and molecular modelling studies of bupivacaine hydrochloride complexation with different cyclodextrin derivates

    NASA Astrophysics Data System (ADS)

    Jug, Mario; Mennini, Natascia; Melani, Fabrizio; Maestrelli, Francesca; Mura, Paola

    2010-11-01

    A novel method, which simultaneously exploits experimental (NMR) and theoretically calculated data obtained by a molecular modelling technique, was proposed, to obtain deeper insight into inclusion geometry and possible stereoselective binding of bupivacaine hydrochloride with selected cyclodextrin derivatives. Sulphobuthylether-β-cyclodextrin and water soluble polymeric β-cyclodextrin demonstrated to be the best complexing agents for the drug, resulting in formation of the most stable inclusion complexes with the highest increase in aqueous drug solubility. The drug-carrier binding modes with these cyclodextrins and phenomena which may be directly related to the higher stability and better aqueous solubility of complexes formed were discussed in details.

  17. 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...

  18. Endocytosis of fluorescent cyclodextrins by intestinal Caco-2 cells and its role in paclitaxel drug delivery.

    PubMed

    Réti-Nagy, Katalin; Malanga, Milo; Fenyvesi, Éva; Szente, Lajos; Vámosi, György; Váradi, Judit; Bácskay, Ildikó; Fehér, Pálma; Ujhelyi, Zoltán; Róka, Eszter; Vecsernyés, Miklós; Balogh, György; Vasvári, Gábor; Fenyvesi, Ferenc

    2015-12-30

    Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the first time that the fluorescent paclitaxel derivative and rhodamine-labeled random methyl-β-cyclodextrin were detected in the same intracellular vesicles after treating cells with their inclusion complex. These results indicate that the endocytosis of cyclodextrin complexes can contribute to drug absorption processes.

  19. 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.

  20. 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.

  1. Dual chiral recognition system involving cyclodextrin derivatives in capillary electrophoresis II. Enhancement of enantioselectivity.

    PubMed

    Jakubetz, H; Juza, M; Schurig, V

    1998-05-01

    The enantiomer separation of hexobarbital was investigated by open tubular electrochromatography (OTEC) using the chiral stationary phase (CSP) CHIRASIL-DEX (a permethylated beta-cyclodextrin covalently linked to a dimethylpolysiloxane) and by cyclodextrin-electrokinetic chromatogaphy (CD-EKC) using anionic beta-cyclodextrin-sulfo-n-propyl ether (SPE-beta-CD) and cationic beta-cyclodextrin-2-hydroxy-3-trimethylammoniumpropyl ether chloride (HTAP-beta-CD) added to the running buffer. By employing two chiral selectors, the enantiomer separation of hexobarbital was then studied simultaneously by OTEC with CHIRASIL-DEX and by CD-EKC with either SPE-beta-CD or HTAP-beta-CD in the dual chiral recognition mode. In conjunction with CHIRASIL-DEX, anionic SPE-beta-CD decreased the chiral separation factor alpha due to compensation of enantioselectivity whereas the cationic additive HTAP-beta-CD increased the chiral separation factor alpha due to enhancement of enantioselectivity. It is concluded that CHIRASIL-DEX imparts an opposite enantioselectivity to the enantiomers of hexobarbital as compared to the charged CDs SPE-beta-CD and HTAP-beta-CD. Unusual peak broadening phenomena are observed in the dual chiral recognition system comprised of CHIRASIL-DEX and HTAP-beta-CD. The possible consequences of accidental dual chiral recognition systems caused by wall stacking effects of the mobile phase additives onto the inner surface of the capillary column are discussed.

  2. Host-guest interaction between pinocembrin and cyclodextrins: Characterization, solubilization and stability

    NASA Astrophysics Data System (ADS)

    Zhou, Shu-Ya; Ma, Shui-Xian; Cheng, Hui-Lin; Yang, Li-Juan; Chen, Wen; Yin, Yan-Qing; Shi, Yi-Min; Yang, Xiao-Dong

    2014-01-01

    The inclusion complexation behavior, characterization and binding ability of pinocembrin with β-cyclodextrin (β-CD) and its derivative 2-hydroxypropyl-β-cyclodextrin (HPβCD) were investigated in both solution and the solid state by means of XRD, DSC, 1H and 2D NMR and UV-vis spectroscopy. The results showed that the water solubility and thermal stability of pinocembrin were obviously increased in the inclusion complex with cyclodextrins. This satisfactory water solubility and high stability of the pinocembrin/CD complexes will be potentially useful for their application as herbal medicines or healthcare products.

  3. 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

  4. Investigation of drug-cyclodextrin complexes by a phase-distribution method: some theoretical and practical considerations.

    PubMed

    Másson, Már; Sigurdardóttir, Birna Vigdís; Matthíasson, Kristján; Loftsson, Thorsteinn

    2005-08-01

    The purpose of the study was to evaluate an octanol-water phase distribution method for investigation of drug/cyclodextrin (D/CD) complexes and to compare stability constant values obtained by this method to values obtained by the phase solubility method. A general equation for determination of 1 : 1 D/CD complex stability constant (K1 : 1) from the slope of a phase-distribution diagram (a diagram of the reciprocal of the apparent partition coefficient vs. the total CD concentration) was derived. The equation accounted for the possible inclusion of the organic solvent in the CD cavity and the gradual saturation of the CD binding with increasing concentration of the guest compound. This method was used to determine K1 : 1 for 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) complexes of hydrocortisone, prednisolone, diazepam, beta-estradiol and diethylstilbestrol. These values were comparable to K1 : 1 values determined by the phase-solubility method. The phase-distribution method could also be applied to determine stability constants for the neutral and ionic forms of the weakly acidic drugs, naproxen and triclosan and the weakly basic drug lidocaine. The phase-distribution method is a very versatile and fast method and has the advantage, compared to the phase-solubility method, that it only requires very small drug samples. Thus, this method would be suitable for screening of new drug candidates.

  5. 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

  6. Structural elucidation of supramolecular alpha-cyclodextrin dimer/aliphatic monofunctional molecules complexes.

    PubMed

    Barrientos, L; Lang, E; Zapata-Torres, G; Celis-Barros, C; Orellana, C; Jara, P; Yutronic, N

    2013-05-01

    The structural elucidation of 2α-cyclodextrin/1-octanethiol, 2α-cyclodextrin/1-octylamine and 2α-cyclodextrin/1-nonanoic acid inclusion complexes by nuclear magnetic resonance (NMR) spectroscopy and molecular modeling has been achieved. The detailed spatial configurations are proposed for the three inclusion complexes based on 2D NMR method. ROESY experiments confirm the inclusion of guest molecules inside the α-cyclodextrin (α-CD) cavity. On the other hand, the host-guest ratio observed was 2:1 for three complexes. The detailed spatial configuration proposed based on 2D NMR methods were further interpreted using molecular modeling studies. The theoretical calculations are in good agreement with the experimental data.

  7. Cyclodextrins in analytical chemistry: host-guest type molecular recognition.

    PubMed

    Szente, Lajos; Szemán, Julianna

    2013-09-03

    Cyclodextrins are utilized in many diverse fields of analytical chemistry, due to their propensity to form reversible inclusion complexes and recognize analytes selectively. This Feature shows how these nanocavities can serve analysts in sample preparation, sensitivity and selectivity improvement, enantio-separation, creating single-molecule sensors, and automatizing DNA sequencing.

  8. 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...

  9. Cyclodextrin-stabilized volatile substances for inhalation therapy.

    PubMed

    Gál-Füzy, M; Szente, L; Szejtli, J; Harangi, J

    1984-08-01

    Diapulmon (Chinoin) which comprise camphor, 1-menthol, eucalyptus oil and quinine dissolved in sunflower oil (Oleum helianthi) is marketed in ampoules of 2 ml but utilized almost exclusively for inhalation therapy. Complexing the active ingredients of Diapulmon with beta-cyclodextrin (beta-CD) a stable non hygroscopic microcrystalline substance is obtained. When this powder sprinkled on hot water, the included volatile compounds are gradually released and the desired pharmacological effect can be brought about.

  10. Cyclodextrins: a new efficient absorbent to treat waste gas streams.

    PubMed

    Blach, Philippe; Fourmentin, Sophie; Landy, David; Cazier, Fabrice; Surpateanu, Gheorghe

    2008-01-01

    Volatile Organic Compounds (VOCs) in the air provoke health and environmental concerns. This paper focuses on the absorption method to treat industrial polluted air loaded with VOCs. The key variable of this treatment being the choice of a suitable liquid absorbent, the aim of this research work is to investigate the effectiveness and the regeneration of a new potential family of absorbent: cyclodextrins (CDs). All CDs derivatives tested are able to decrease the Henry's law constant of toluene: a reduction of volatility up to 95% may be obtained, depending on CD nature and concentration. Moreover, absorption experiments show that beta-CD, which presents the highest absorption ability, is 250 time more efficient than water. The absorption efficiency is not totally correlated with static experiments, suggesting that, in addition to Henry's law constants and inclusion compounds stability, toluene diffusion into such solutions has to be taken into account. It is also to be noted that salt and pH variations seem to have little influence on the absorption capacity of CDs, which may be of great interest for industrial applications. Finally, since production of solid compounds was not observed during these experiments and since temperature decreases the capture ability in a drastic way, regeneration of the washing solution can be achieved by heating the solution in combination with air stripping.

  11. Electrospun Fibers of Cyclodextrins and Poly(cyclodextrins).

    PubMed

    Costoya, Alejandro; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2017-02-03

    Cyclodextrins (CDs) can endow electrospun fibers with outstanding performance characteristics that rely on their ability to form inclusion complexes. The inclusion complexes can be blended with electrospinnable polymers or used themselves as main components of electrospun nanofibers. In general, the presence of CDs promotes drug release in aqueous media, but they may also play other roles such as protection of the drug against adverse agents during and after electrospinning, and retention of volatile fragrances or therapeutic agents to be slowly released to the environment. Moreover, fibers prepared with empty CDs appear particularly suitable for affinity separation. The interest for CD-containing nanofibers is exponentially increasing as the scope of applications is widening. The aim of this review is to provide an overview of the state-of-the-art on CD-containing electrospun mats. The information has been classified into three main sections: (i) fibers of mixtures of CDs and polymers, including polypseudorotaxanes and post-functionalization; (ii) fibers of polymer-free CDs; and (iii) fibers of CD-based polymers (namely, polycyclodextrins). Processing conditions and applications are analyzed, including possibilities of development of stimuli-responsive fibers.

  12. 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.

  13. Synchronous wavelength scanning room temperature phosphorescence: Comparison of cyclodextrin and micellar media

    NASA Astrophysics Data System (ADS)

    Femia, Robert A.; Love, L. J. Cline

    Application of synchronous wavelength scanning to two fluid phase room temperature phosphorescence (RTP) techniques using β-cyclodextrin and micelles are evaluated and compared. The selectivity, sensitivity, susceptibility to light scattering interference and classes of compounds amenable to determination by the two RTP approaches are discussed. Synchronous wavelength scanning cyclodextrin RTP studies focus on its usefulness for identification of nitrogen heterocyclic phosphors. Spectral resolution is improved in both RTP techniques by second derivative manipulation of the digitally stored synchronous spectra. A significant scatter interference resulting from turbidity produced by the cyclodextrin inclusion complexes imposes constraints on the selectivity and sensitivity achievable with the cyclodextrin medium, especially when using synchronous wavelength scanning. Generally, micelle-induced RTP was found to be superior to cyclodextrin-induced RTP for analysis of various mixtures of the 12 heterocyclics and 15 carbocyclics studied, as well as for a mixture of the drug, propranolol, and its 4-hydroxy metabolite.

  14. 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.

  15. Effect of cyclodextrins and polymers on triclosan availability and substantivity in toothpastes in vivo.

    PubMed

    Loftsson, T; Leeves, N; Bjornsdottir, B; Duffy, L; Masson, M

    1999-12-01

    The aqueous solubility of triclosan is only about 10 microg/mL. This very low solubility can hamper its biological activity in the oral cavity, which could explain the mixed clinical results obtained from triclosan toothpaste trials. Triclosan availability in a silica-based toothpaste was improved through cyclodextrin solubilization. The triclosan in vivo availability was optimized through a series of phase-solubility studies and triclosan release studies. It was found that in toothpastes, natural beta-cyclodextrin (betaCD) was just as good a solubilizer as the more water-soluble betaCD derivatives. Furthermore, the amount of cyclodextrin could be reduced by as much as 60% through the addition of a small amount of carboxymethylcellulose (CMC), without affecting triclosan release from the toothpaste. Optimally, cyclodextrins resulted in an almost 3-fold enhancement of triclosan availability compared to an identical toothpaste containing no cyclodextrin. In vivo studies in humans showed that replacing triclosan with triclosan/betaCD in the toothpaste resulted in only moderate improvement in triclosan substantivity. However, replacing triclosan with triclosan/betaCD/CMC complex resulted in significant improvement in triclosan substantivity. Furthermore, the in vivo studies showed that replacing free triclosan with triclosan/betaCD/CMC complex resulted in an almost 3-fold increase in initial triclosan concentration in saliva after brushing and about 2-fold increase in duration of activity.

  16. Surface modification of cellulose fiber via supramolecular assembly of biodegradable polyesters by the aid of host-guest inclusion complexation.

    PubMed

    Zhao, Qiang; Wang, Shufang; Cheng, Xinjian; Yam, Richard C M; Kong, Deling; Li, Robert K Y

    2010-05-10

    In this article, we report a novel surface modification method for cellulose fiber that is based on supramolecular assembly. Beta-cyclodextrin (beta-CD) was first covalently grafted onto the fiber surface. Then poly(epsilon-caprolactone) (PCL) oligomers having both ends capped with adamantane motifs (i.e., PCL-AD) were immobilized to the cellulose fiber surface through the host-guest inclusion complexation between beta-CD and AD motif. FTIR-ATR and XPS analyses confirmed the successful assembly of PCL-ADs, which was further supported by the increasing trend of weight gain with the concentration of CDs on the fiber surface. Contact angle and TGA measurements reflect the enhanced hydrophobicity and thermal stability of the cellulose fiber as a consequence of this modification. The morphologies of the cellulose fiber before and after the assembly process have also been compared by SEM.

  17. [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.

  18. Mode of encapsulation of linezolid by β-cyclodextrin and its role in bovine serum albumin binding.

    PubMed

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

    2015-01-22

    We describe, in this article, the associative interaction between Linezolid and β-Cyclodextrin, and the influence of β-Cyclodextrin on Linezolid's binding to Bovine serum albumin. β-Cyclodextrin forms a 1:1 inclusion complex with Linezolid, with a binding constant value of 3.51×10(2)M(-1). The binding is studied using ultraviolet-visible absorption, fluorescence, nuclear magnetic resonance, and rotating-frame overhauser effect spectroscopic techniques. The amide substituent on the oxazolidinone ring of Linezolid is involved in its binding to β-Cyclodextrin. The binding of the Linezolid to bovine serum albumin, in the absence and the presence of β-Cyclodextrin, is studied by analyzing the fluorescence quenching and Förster resonance energy transfer. The Stern-Volmer quenching constant, the binding constant, and energy transfer occurring on the interaction of the Linezolid with BSA are found to be smaller in the presence of β-Cyclodextrin than in water.

  19. Carotenoid:β-cyclodextrin stability is independent of pigment structure.

    PubMed

    Fernández-García, Elisabet; Pérez-Gálvez, Antonio

    2017-04-15

    Carotenoids refer to a wide class of lipophilic pigments synthesized by plants, exert photoprotective and antioxidant properties that are lost upon carotenoid degradation. Their inclusion into hydrophilic host-molecules could improve their stability. Cyclodextrins, provide a hydrophobic cavity in the core of their structure while the outer configuration is suitable with aqueous environments. Carotenoids can accommodate into the hydrophobic core of cyclodextrins and therefore, they are protected from exogenous stress. Literature reported that carotenoid structure could modulate stability of the complexes, however no conclusions can be drawn as the studies performed so far were not completely analogous. We describe the synthesis of several carotenoids/β-CDs inclusion complexes and provide experimental evidences that β-CDs inclusion renders these compounds more stability towards the oxidizing agents (2,2'-azobis, 2-methylpropionamidine dihydrochloride and hydrogen peroxide). Esterified carotenoids were also used in this work to screen the influence of this particular structural configuration of xanthophylls against oxidation.

  20. Assessment of ternary iron-cyclodextrin-2-naphthol complexes using NMR and fluorescence spectroscopies

    NASA Astrophysics Data System (ADS)

    Zheng, Weixi; Tarr, Matthew A.

    2006-12-01

    Recent research has indicated that ternary complexes can be formed among carboxymethyl-β-cyclodextrin, certain polycyclic aromatic hydrocarbons (PAHs) (e.g. anthracene and 2-naphthol), and Fe 2+ in aqueous solution. The formation of these ternary complexes has been suggested as the reason for improved reaction efficiency in iron catalyzed Fenton degradation (H 2O 2 + Fe 2+ → rad OH + OH - + Fe 3+) of PAHs and other pollutants. In the present work, several other cyclodextrins were examined to determine their ability to form similar ternary complexes with 2-naphthol and Fe 2+. Fluorescence and NMR techniques were employed in this study. Results showed that hydroxypropyl-β-cyclodextrin, β-cyclodextrin, and α-cyclodextrin were able to encapsulate 2-naphthol molecules, but their binding with Fe 2+ was weak. On the contrary, sulfated-β-cyclodextrin has significant binding with Fe 2+, but it showed little inclusion of 2-naphthol molecules. Consequently, none of these four cyclodextrins formed significant amounts of ternary complexes in aqueous solution. The techniques used in this study provide useful methods for assessing the ability of cyclodextrins to form ternary complexes with guest compounds and metal ions.

  1. Strong guest binding by cyclodextrin hosts in competing nonpolar solvents and the unique crystalline structure.

    PubMed

    Kida, Toshiyuki; Iwamoto, Takuya; Fujino, Yoshinori; Tohnai, Norimitsu; Miyata, Mikiji; Akashi, Mitsuru

    2011-09-02

    6-O-Modified β-cyclodextrins, such as heptakis(6-O-triisopropylsilyl)-β-cyclodextrin (TIPS-β-CD) and heptakis(6-O-tert-butyldimethylsilyl)-β-cyclodextrin (TBDMS-β-CD), formed 2:1 inclusion complexes with pyrene in benzene and cyclohexane with high association constants. The X-ray crystalline structure of the TIPS-β-CD-pyrene complex obtained from the benzene solution showed that one pyrene molecule was incorporated in the form of a sandwich-type complex with two benzene molecules within the cavity of the dimer formed by two TIPS-β-CD molecules.

  2. Complexation of phytochemicals with cyclodextrin derivatives - An insight.

    PubMed

    Suvarna, Vasanti; Gujar, Parul; Murahari, Manikanta

    2017-04-01

    Natural compounds have been attracting huge attention because of their broad therapeutic properties with specificity in their action in human health care as functional foods, pharmaceuticals and nutraceuticals. However poor bioavailability and reduced bioactivity attributed to poor solubility and instability is the major drawback hindering the incorporation of these therapeutically potential molecules in novel drug delivery systems. Based on the findings of reported research investigations; complexation of poorly water soluble phytochemicals with cyclodextrins has emerged to be a promising approach to improve their aqueous solubility, stability, rate of dissolution and bioavailability. The present article summarizes the encapsulation of natural compounds ranging from various flavonoids, phenolic derivatives, coumestans to triterpenes, with cyclodextrin and their derivatives. Also the article highlights the method of complexation, complexation ability, drug solubility, stability, bioavailability and safety aspects of reported natural compounds. Additionally we present the glimpses of patents published in recent 10-15 years to highlight the significance of inclusion of phytochemicals in cyclodextrins. In patents narrated, improvement in stability and solubility of curcumin by complexation with alkyl ether derivative of gamma-cyclodextrin is claimed. Another patent mentioned, complexation of artemisinins with β-cyclodextrin, improved the stability and integrity of peroxide part of artemisinins for long period. On the other hand the complex of dihydromyricetin with γ-CD has shown improved solubility, stability and bioavailability. Thus it can be concluded that phytochemicals have multiple biological activities with broader safety index and improvement of their solubility will be truly beneficial to aid their effective delivery in healthcare.

  3. Natural cyclodextrins as efficient boosters of the chemiluminescence of luminol and isoluminol: exploration of potential applications.

    PubMed

    Maeztu, Raquel; Tardajos, Gloria; González-Gaitano, Gustavo

    2010-03-04

    The chemiluminescent oxidation of luminol (LUM) and isoluminol (ISOL) is notably enhanced, both in intensity and duration, in the presence of natural cyclodextrins (alpha-, beta-, gamma-CD). The experiments have considered some of the most widespread applications of these compounds: the determination of metal cations and the revealing of bloodstains by oxidation with hydrogen peroxide in alkaline solution in the presence of Co(II), Fe(III), human hemoglobin, and blood, in order to explore potential applications. The largest enhancement in the emitted intensity occurs for the reaction of LUM with Co(II) in the presence of beta-CD. The use of the more soluble gamma-CD permits to expand the range of concentration and obtain more intense emission, although soluble derivatives of the beta-CD (methyl, hydroxypropyl-beta-CD, and a soluble cross-linked epichlorhydrin polymer) do not improve the chemiluminescence (CL) yield. In the case of hemoglobin and diluted human blood, the CDs aid in producing more light but only at high concentration of CDs, with a more lasting luminescence, up to three times longer. The changes in CL when glucose is used instead, much lower than with any of the CDs, imply that the cyclic structure of these oligosaccharides plays a key factor in the boosting of the emission. The results are explained in terms of the binding between the luminescent intermediate of the reaction, 3-aminophthalate (3-AP) and the CD, rather than to the luminescent reactant itself. The association constants obtained by steady-state fluorescence by assuming 1:1 stoichiometries reveal that the most stable association occurs between beta-CD and the intermediate, in accordance with the trend in the chemiluminescence. The topology of the complex deduced via ROESY experiments confirms a shallow inclusion of the double-charged intermediate by the primary rim of the CD, which accounts for the low stability of the complexes.

  4. A family of single-isomer, dicationic cyclodextrin chiral selectors for capillary electrophoresis: mono-6(A)-ammonium-6(C)-butylimidazolium-β-cyclodextrin chlorides.

    PubMed

    Dai, Yun; Wang, Shuye; Zhou, Jie; Tang, Jian; Tang, Weihua

    2013-03-01

    The first member of the single-isomer, dicationic cyclodextrin (CD) family, 6(A)-ammonium-6(C)-butylimidazolium-β-cyclodextrin chlorides (AMBIMCD), has been synthesized, analytically characterized, and used to separate a variety of acidic enantiomers and amino acids by CE. Starting from mono-6(A)-azido-β-cyclodextrin, the cationic imidazolium and ammonium moieties were subsequently introduced onto primary ring of β-cyclodextrin via nucleophilic addition and Staudinger reaction. The analytically pure AC regio-isomer CD was further obtained via column chromatography. This dicationic CD exhibited excellent enantioselectivities for selected analytes at concentration as low as 0.5 mM, which were even better than those of its mono-imidazolium or ammonium-substitued counterpart CDs at 10 equivalent concentrations. The effective mobilities of all studied analytes were found to decrease with the concentration of AMBIMCD. Inclusion complexation in combination with eletrostatic interactions seemed to account for the enhanced chiral discrimination process.

  5. Anesthetic related advances with cyclodextrins.

    PubMed

    Welliver, Mark; McDonough, John

    2007-03-02

    Cyclodextrins encapsulate and electrostatically bind to lipophilic molecules. The exterior of cyclodextrins are water-soluble and maintain aqueous solubility despite encapsulation of non-aqueous soluble molecules. This unique ability to encapsulate lipophilic molecules and maintain water solubility confers numerous pharmacologic advantages for both drug delivery and removal. Cyclodextrins, a component part of supramolecular chemistry, may be in its infancy of anesthetic application but recent advances have been described as novel and revolutionary. A review of current research coupled with an understanding of cyclodextrin properties is necessary to fully appreciate the current uses and future potentials of these unique molecules.

  6. Oil-cyclodextrin based beads for oral delivery of poorly-soluble drugs.

    PubMed

    Hamoudi, M C; Bochot, A

    2014-01-01

    The main interest of cyclodextrins results from their ability to form inclusion complexes with hydrophobic molecules. This property is employed in pharmaceutical industry to facilitate the formulation of poorly-soluble and/or fragile drugs. Cyclodextrins are also used to form or stabilise dispersed systems. An original multiparticulate system named "beads" is obtained thanks to the interactions occurring between the molecules of α cyclodextrin and the triglycerides of vegetable oils. Beads are prepared by a simple process involving the external shaking of a mixture of an aqueous solution of α cyclodextrin with soybean oil. This is done without any organic solvent or surface-active agent. Once freezedried, beads have a diameter of 1.6 mm and a high lipid content. They consist in a partially crystalline matrix of cyclodextrin surrounding microdomains of oil. The coating of beads with a layer of α cyclodextrin improves their resistance in gastro- intestinal fluids and prolongs the release of drugs. Beads can also be manufactured from mineral oils with α cyclodextrin and from silicone oils with γ cyclodextrin. Poorly-soluble drugs which do not form inclusion complexes with α cyclodextrin are encapsulated in beads with high efficiency and drug loading. In rats, the oral bioavailability of isotretinoin is twofold enhanced with uncoated beads as compared to the lipid content of a soft capsule. The relative oral bioavailability of indomethacin is improved with both coated and uncoated beads versus a commercial hard capsule. Beads demonstrate an important potential for the encapsulation of poorly-soluble and/or fragile compounds and their delivery by oral route.

  7. Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly(anhydride) nanoparticles.

    PubMed

    Agüeros, M; Zabaleta, V; Espuelas, S; Campanero, M A; Irache, J M

    2010-07-01

    The aim of this work was to study the oral bioavailability in rats of paclitaxel (PTX) when encapsulated as a complex with cyclodextrins in poly(anhydride) nanoparticles (NP). For this purpose three different cyclodextrins were selected: beta-cyclodextrin (CD), 2-hydroxypropyl-beta-cyclodextrin (HPCD) and 6-monodeoxy-6-monoamino-beta-cyclodextrin (NHCD). A single dose of 10mg paclitaxel per kg body weight as PTX-cyclodextrin nanoparticles was used. Plasma curves were characterised by a plateau of paclitaxel concentration close to the C(max) from T(max) till 24h post-administration. For PTX-CD NP and PTX-HPCD NP, these sustained levels of the anticancer drug were found to be between 27 and 33-fold higher than the reported value of drug activity whereas the relative oral bioavailability of paclitaxel was calculated to be higher than 80%. These facts would be directly related with a synergistic effect obtained by the combination of the bioadhesive properties of poly(anhydride) nanoparticles and the inhibitory effect of cyclodextrins on the activity of P-glycoprotein and cythocrome P450.

  8. 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.

  9. Ground- and excited-state structural orientation of 2-(2`-hydroxyphenyl)benzazoles in cyclodextrins

    SciTech Connect

    Roberts, E.L.; Dey, J.; Warner, I.M.

    1996-12-12

    The effects of {alpha}-, {beta}-, {gamma}-, and 2,6-di-O-methyl-{beta}-cyclodextrins (CDs) on the ground- and excited-state properties of 2-(2`-hydroxyphenyl)benzoxazole, 2-(2`-hydroxyphenyl)benzothiazole, and 2-(2`-hydroxyphenyl)benzimidazole in aqueous media are investigated. Steady-state fluorescence measurements are used to characterize the interaction of CDs with these azoles. Absorbance measurements indicate increased solubility of the azoles in aqueous solutions of CDs. Measurements of acidity constants (pK{sub a}) and data from induced circular dichroism indicate increased ground- and excited-state acidities of the phenolic protons of the molecules in the presence of CDs and axial orientation of the molecules within the CD cavity, respectively. The data further suggest a planar structure for HBO and a twisted confirmation for both HBT and HBI. The association constants of the inclusion complexes have also been estimated. These studies are further supplemented by comparative spectroscopic studies of 2-(2`-methoxyphenyl)benzothiazole in aqueous solutions of CDs. On the basis of the spectral data acquired, it is believed that the HBA molecules exist as zwitterionic tautomers in the presence of CDs. 35 refs., 6 figs., 2 tabs.

  10. Cyclodextrin, an efficient tool for trans-anethole encapsulation: chromatographic, spectroscopic, thermal and structural studies.

    PubMed

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

    2014-12-01

    Inclusion complexes of trans-anethole (AN) with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RAMEB) and a low methylated-β-cyclodextrin (CRYSMEB) were investigated in aqueous solution by static headspace gas chromatography (SH-GC), phase solubility study, UV-Visible, (1)H NMR and (2D) ROESY NMR spectroscopies. The obtained results indicated the formation of 1:1 inclusion complex for all the studied CDs. Water solubility of AN was significantly improved upon complexation with CDs as demonstrated by phase solubility and retention studies. Solid inclusion complexes were prepared by the freeze-drying method and the encapsulation of AN was confirmed by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies. Moreover, the degradation of AN, induced by UVC irradiation, was markedly reduced by the formation of CD inclusion complexes. Results showed that encapsulation in CDs was an efficient way to increase solubility and stability of AN, thereby making it valuable for food or pharmaceutical applications.

  11. Complex and mixture of β-cyclodextrin with diazepam characterised by ¹H NMR and atom-atom potential methods.

    PubMed

    Pajzderska, A; Mielcarek, J; Wąsicki, J

    2014-10-29

    Inclusion complex of β-cyclodextrin with diazepam and a physical mixture of these components were studied by solid-state (1)H NMR. The activation barrier for reorientation of the methyl group in the diazepam molecule was found not changed by complex formation with β-cyclodextrin. The complex formation resulted in a decrease in the number of water molecules and affected the relaxation time of β-cyclodextrin. By the atom-atom potential method the most probable configuration of the diazepam molecule inside β-cyclodextrin cavity was proposed.

  12. Cyclodextrins as catalysts for the removal of cholesterol from macrophage foam cells.

    PubMed Central

    Atger, V M; de la Llera Moya, M; Stoudt, G W; Rodrigueza, W V; Phillips, M C; Rothblat, G H

    1997-01-01

    Low concentrations of cyclodextrins (< 1.0 mM) added to serum act catalytically, accelerating the exchange of cholesterol between cells and lipoproteins. J774 macrophages incubated with serum and 2-hydroxypropyl-beta-cyclodextrin (< or = 1 mM) released fivefold more labeled cholesterol than with serum alone. Increased efflux was not accompanied by a change in cell cholesterol mass; thus, cyclodextrin functioned as a cholesterol shuttle, enhancing cholesterol bidirectional flux without changing the equilibrium cholesterol distribution between cells and medium. The addition of phospholipid vesicles to serum and cyclodextrin shifted the equilibrium distribution to favor the medium, producing rapid and extensive depletion of cell cholesterol mass. The combination of serum, phospholipid vesicles, and cyclodextrin also stimulated the rapid clearance of both free and esterified cholesterol from mouse peritoneal macrophages loaded with free and esterified cholesterol. This study: (a) demonstrates that a compound can function as a catalyst to enhance the movement of cholesterol between cells and serum, (b) illustrates the difference between cholesterol exchange and net transport in a cell/serum system, (c) demonstrates how net movement of cholesterol is linked to concentration gradients established by phospholipids, (d) provides a basis for the development of the shuttle/sink model for the first steps in reverse cholesterol transport, (e) validates the model using artificial shuttles (cyclodextrins) and sinks (large unilamellar vesicles), and (f) suggests that cyclodextrin-like cholesterol shuttles might be of pharmacological significance in treating unstable atherosclerotic plaques. PMID:9045882

  13. Enhanced enzyme activities of inclusion bodies of recombinant beta-galactosidase via the addition of inducer analog after L-arabinose induction in the araBAD promoter system of Escherichia coli.

    PubMed

    Jung, Kyung-Hwan

    2008-03-01

    We observed that an inclusion body (IB) of recombinant beta-galactosidase that was produced by the araBAD promoter system in Escherichia coli (E. coli) showed enzyme activity. In order to improve its activity, the lowering of the transcription rate of the beta-galactosidase structural gene was attempted through competition between an inducer (L-arabinose) and an inducer analog (D-fucose). In the deep-well microtiter plate culture and lab-scale fermentor culture, it was demonstrated that the addition of D-fucose caused an improvement in specific beta-galactosidase production, although beta-galactosidase was produced as an IB. In particular, the addition of D-fucose after induction led to an increase in the specific activity of beta-galactosidase IB. Finally, we confirmed that the addition of D-fucose after induction caused changes in the structure of beta-galactosidase IB, with higher enzyme activity. Based on these results, we expect that an improved enzyme IB will be used as a biocatalyst of the enzyme bioprocess, because an enzyme IB can be purified easily and has physical durability.

  14. 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.

  15. 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.

  16. Formulation, optimization and evaluation of curcumin-β-cyclodextrin-loaded sponge for effective drug delivery in thermal burns chemotherapy.

    PubMed

    Kaur, Navdeep; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-09-01

    The present study was designed to determine the role of curcumin-β-cyclodextrin-loaded sponge on burn wound healing in rats. Curcumin-β-cyclodextrin complex was prepared by the solvent evaporation encapsulation method. Molecular inclusion complex of curcumin-β-cyclodextrin was incorporated into gelatin sponge. The developed sponge was characterized for drug entrapment, drug release and morphology. The biological activity of optimized formulation was determined on burn wounds which were made on rats. The burn wound healing efficacy was analyzed through physical and histological changes observed at the wound sites. There was a significant decrease in rate of wound contraction in experimental groups then the control group. Curcumin-β-cyclodextrin-loaded sponge treated wound was found to heal in rate comparable to marketed formulation with no sign of adverse consequence. The result clearly substantiates the beneficial effects of curcumin-β-cyclodextrin-loaded sponge in the acceleration of wound healing.

  17. Practical considerations in development of solid dosage forms that contain cyclodextrin.

    PubMed

    Miller, Lee A; Carrier, Rebecca L; Ahmed, Imran

    2007-07-01

    The following is a review of the literature that addresses the use of cyclodextrin in solid dosage forms. Care was taken to exclude physical and chemical characteristics of cyclodextrin, which have been discussed in the literature. A flow diagram is provided to outline the decision-making steps that are involved in the development process. Both preparation of physical mixtures and inclusion complexes are considered. Analytical techniques to determine the presence of inclusion complexes, the effect of other excipients on complex formation, the effect of size limitation of solid dosages forms, powder processing, and storage of solid dosage forms are discussed.

  18. Host-guest interaction between new nitrooxoisoaporphine and β-cyclodextrins: Synthesis, electrochemical, electron spin resonance and molecular modeling studies

    NASA Astrophysics Data System (ADS)

    Pérez-Cruz, Fernanda; Aguilera-Venegas, Benjamín; Lapier, Michel; Sobarzo-Sánchez, Eduardo; Uriarte Villares, Eugenio; Olea-Azar, Claudio

    2013-02-01

    A new nitrooxoisoaporphine derivative was synthetized and characterized by cyclic voltammetry and electron spin resonance. Its aqueous solubility was improved by complexes formation with β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin and (2-hydroxypropyl)-β-cyclodextrin. In order to assess the inclusion degree reached by nitrooxoisoaporphine in cyclodextris cavity, the stability constants of formation of the complexes were determined by phase-solubility measurements obtaining in all cases a type-AL diagram. Moreover, electrochemical studies were carried out, where the observed change in the EPC value indicated a lower feasibility of the nitro group reduction. Additionally, a detailed spatial configuration is proposed for inclusion of derivate within the cyclodextrins cavity by 2D NMR techniques. Finally, these results are further interpreted by means of molecular modeling studies. Thus, theoretical results are in complete agreement with the experimental data.

  19. Cholesterol does not affect the toxicity of amyloid beta fragment but mimics its effect on MTT formazan exocytosis in cultured rat hippocampal neurons.

    PubMed

    Abe, K; Saito, H

    1999-12-01

    It has recently been reported that methyl-beta-cyclodextrin-solubilized cholesterol protects PC12 cells from amyloid beta protein (Abeta) toxicity. To ask if this is the case in brain neurons, we investigated its effect in primary cultured rat hippocampal neurons. In basal culture conditions with no addition of Abeta, methyl-beta-cyclodextrin-solubilized cholesterol at concentrations of 30-100 microM was toxic to neurons, but at concentrations of 1-10 microM promoted neuronal survival. Methyl-beta-cyclodextrin-solubilized cholesterol at 1-10 microM was also effective in protecting neurons from toxicity of 20 microM Abeta. However, these effects were all mimicked by methyl-beta-cyclodextrin alone, but not by cholesterol solubilized by dimethylsulfoxide or ethanol. The effects of methyl-beta-cyclodextrin-solubilized cholesterol on neuronal survival and Abeta toxicity are probably attributed to the action of methyl-beta-cyclodextrin, but not cholesterol. Alternatively, we found that methyl-beta-cyclodextrin-solubilized cholesterol at lower concentrations ( > 10 nM) inhibited cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide (MTT) by promoting the exocytosis of MTT formazan. This effect was shared by dimethylsulfoxide- or ethanol-solubilized cholesterol, but not by methyl-beta-cyclodextrin, supporting that it is attributed to the action of cholesterol. These results suggest that cholesterol does not protect neurons from Abeta toxicity, or rather inhibits cellular MTT reduction in a similar manner to Abeta.

  20. Separation of mycotoxins, polycyclic aromatic hydrocarbons, quinones, and heterocyclic compounds on cyclodextrin bonded phases: an alternative LC packing

    SciTech Connect

    Armstrong, D.W.; Alak, A.; De Mond, W.; Hinze, W.L.; Riehl, T.E.

    1985-01-01

    ..beta..-Cyclodextrin and gamma-cyclodextrin chiral bonded phases were previously shown to be useful in the separation of enantiomers, diastereomers and structural isomers. In this work it is demonstrated that these stationary phases are also useful in more routine separations. As such, they provide an alternative to the popular reverse phase packings. Because the selectivity of cyclodextrin packings is often unique they can be used to compliment conventional columns, particularly when separating complex mixtures where peak overlap is a problem. The separation of several important classes of compounds is used to demonstrate the general utility of this packing.

  1. Fenton degradation assisted by cyclodextrins of a high molecular weight polycyclic aromatic hydrocarbon benzo[a]pyrene.

    PubMed

    Veignie, Etienne; Rafin, Catherine; Landy, David; Fourmentin, Sophie; Surpateanu, Gheorghe

    2009-09-15

    This paper investigates the effect of native beta-cyclodextrin (beta-CD) and its CD derivatives, such as hydroxypropyl-beta-cyclodextrin (HPBCD) and randomly methylated-beta-cyclodextrin (RAMEB), on the solubilization of a high molecular weight polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP) and on its degradation by Fenton's reaction. The results show that BaP apparent solubility was significantly increased in the presence of cyclodextrin (CD) in the following order: beta-CDcyclodextrin to solubilize BaP. In the presence of a radical scavenger (mannitol), BaP Fenton degradation was inhibited with RAMEB but not in the presence of HPCD. Molecular modelisation was used to visualize the steric complementarity of these host-guest systems. No significant difference of encapsulation between the two modified CDs was observed. Nevertheless, the results suggest a probable existence of a ternary complex HPCD-BaP-iron permitting the generation of hydroxyl radicals in close proximity to BaP. On the basis of these results, it appears that HPCD may be useful for developing targeted BaP degradation system.

  2. Effect of β-cyclodextrin on the molecular properties of myricetin upon nano-encapsulation: insight from optical spectroscopy and quantum chemical studies.

    PubMed

    Chakraborty, Sandipan; Basu, Soumalee; Basak, Soumen

    2014-01-01

    Myricetin, a bioactive plant flavonol, readily forms inclusion complex with the drug delivery vehicle beta-cyclodextrin (β-CD). Appearance of typical "dual emission", consisting of normal (470 nm) and ESIPT tautomer (530 nm) bands, with concomitant rise in fluorescence intensity and dramatically blue shifted normal fluorescence of myricetin with increasing β-CD concentration, indicates facile entry of myricetin into the cavity of β-CD. The stoichiometry of the inclusion complex has been established to be equimolar (1:1), with an equilibrium constant of 439 ± 18 M(-1) at 25 °C. The driving force of inclusion is attributed to strong van der Waals interaction and formation of hydrogen bond between host (β-CD) and guest (myricetin). Both experimental and theoretical studies indicate that myricetin possibly incorporates within β-CD through its benzoyl moiety. Inclusion in β-CD increases the antioxidant potency of myricetin which has been attributed to the less delocalised HOMO and reduced HOMO-LUMO energy gap in the confined state.

  3. 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.

  4. Macromolecular recognition and macroscopic interactions by cyclodextrins.

    PubMed

    Harada, Akira; Takashima, Yoshinori

    2013-10-01

    Herein macromolecular recognition by cyclodextrins (CDs) is summarized. Recognition of macromolecules by CDs is classified as main-chain recognition or side-chain recognition. We found that CDs form inclusion complexes with various polymers with high selectivity. Polyrotaxanes in which many CDs are entrapped in a polymer chain were prepared. Tubular polymers were prepared from the polyrotaxanes. CDs were found to recognize side-chains of polymers selectively. CD host polymers were found to form gels with guest polymers in water. These gels showed self-healing properties. When azobenzene was used as a guest, the gel showed sol-gel transition by photoirradiation. When ferrocene was used, redox-responsive gels were obtained. Macroscopic self-assembly through molecular recognition has been discovered. Photoswitchable gel association and dissociation have been observed.

  5. 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

  6. 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

    2014-11-04

    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.

  7. Spectral characteristics of tramadol in different solvents and β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Anton Smith, A.; Manavalan, R.; Kannan, K.; Rajendiran, N.

    2009-10-01

    Effect of solvents and β-cyclodextrin on the absorption and fluorescence spectra of tramadol drug has been investigated and compared with anisole. The solid inclusion complex of tramadol with β-CD is investigated by FT-IR, 1H NMR, scanning electron microscope (SEM), DSC and semiempirical methods. The thermodynamic parameter (Δ G) of inclusion process is determined. A solvent study shows (i) the spectral behaviour of both tramadol and anisole molecules is similar to each other and (ii) the cyclohexanol group in tramadol is not effectively conjugated with anisole group. However, in β-CD, due to space restriction of the CD cavity, a weak interaction is present between the above groups in tramadol. β-Cyclodextrin studies show that tramadol forms 1:2 inclusion complex with β-CD. A mechanism is proposed for the inclusion process.

  8. 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.

  9. beta-Sonogel-carbon electrodes: a new alternative for the electrochemical determination of catecholamines.

    PubMed

    Izaoumen, Nissrin; Cubillana-Aguilera, Laura M; Naranjo-Rodríguez, Ignacio; de Cisneros, José L Hidalgo-Hidalgo; Bouchta, Dounia; Temsamani, Khalid R; Palacios-Santander, José M

    2009-04-30

    In this work, a new alternative for the electrochemical determination of catecholamines based on beta-cyclodextrin-Sonogel-Carbon electrodes is reported. The incorporation of beta-CD and graphite in the preparation of the Sonogel-Carbon material leads to a modification of the electrode surface properties which causes a significant increase in the oxidation peak current of biomolecules such as dopamine, L-epinephrine, D,L-norepinephrine and catechol. This phenomenon might be attributed to the formation of an inclusion complex between beta-CD and the catecholamines. The amount of beta-CD necessary to form the Sonogel electrode was studied and optimization of electrochemical parameters, perm selectivity and mechanical stability of the sensor are discussed. Scanning electron microscopy and electrochemical impedance spectroscopy measurements were employed to characterize the electrical parameters and the structural properties of the new electrode surface, respectively. Cyclic voltammetry (CV) and Adsorptive differential pulse voltammetry (AdDPV) measurements were also used to explore the electrochemical behaviour of the electrode versus the quoted catecholamines. The beta-CD-Sonogel-Carbon electrode offers fast and linear responses towards dopamine, norepinephrine, epinephrine and catechol, with good and low detection limits: 0.164, 0.294, 0.699 and 0.059 micromol L(-1), respectively.

  10. Detecting Ni(II) in aqueous solution by 3-(2-pyridyl)-[1,2,3]triazolo[1,5-a]pyridine and dimethyl-β-cyclodextrin.

    PubMed

    Jullian, Carolina; Fernández-Sandoval, Samuel; Rojas-Aranguiz, Max; Gómez-Machuca, Horacio; Salgado-Figueroa, Paola; Celis-Barros, Cristián; Zapata-Torres, Gerald; Adam, Rosa; Abarca, Belén

    2014-07-17

    A new supramolecular sensitizer for nickel(II) ion in aqueous solution based on a pyridyltriazolopyridine-cyclodextrin inclusion complex is proposed. The inclusion complexation behavior, characterization and binding ability of pyridyltriazolopyridine (PTP) with dimethyl-β-cyclodextrin (DMβCD) has been investigated both in solution and solid state by means of absorption, fluorescence, (1)H NMR, DSC, and molecular modeling methods. The stoichiometry of the inclusion complex is 1:1, and the thermodynamic studies indicate that the inclusion of PTP is mainly an entropic driven process. The 2D NMR studies revealed that the pyridyl-triazolopyridine is included by both sides of cyclodextrin which are in good agreement with the docking results. The fluorescence changes upon addition of divalent cations to the inclusion complex indicate a high selectivity and sensitivity for Ni(2+) by fluorescence quenching in neutral aqueous solution.

  11. 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.

  12. The Role of Inclusion Binding Contributions for β-Cyclodextrin Polymers Cross-Linked with Divinyl Sulfone?--A Comment on Morales-Sanfrutos et al. Entitled "Divinyl Sulfone Cross-Linked Cyclodextrin-Based Polymeric Materials: Synthesis and Applications as Sorbents and Encapsulating Agents", Molecules, 2015, 20, 3565-3581.

    PubMed

    Wilson, Lee D; Mohamed, Mohamed H; McMartin, Dena W

    2016-01-14

    This commentary reports on a recent scientific study reported in this journal (cf. Molecules 2015, 20(3), 3565-3581). Some key scientific issues that require further explanation and clarification in the former article are as follows: (i) the relationship between the inclusion site accessibility and the level of cross-linking employed are brought into question for the case of α-CD and β-CD cross-linked adsorbent materials; (ii) the binding affinity of the CD/guest complexes were not related to the isotherm parameters for the CD-polymer/guest systems; (iii) the limited molecular level structural characterization of the cross-linked polymer materials; and (iv) the interpretation of the adsorption isotherm results by the authors.

  13. Development of Orodispersible Tablets of Candesartan Cilexetil-β-cyclodextrin Complex

    PubMed Central

    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

  14. Binding of a chromen-4-one Schiff's base with bovine serum albumin: capping with β-cyclodextrin influences the binding.

    PubMed

    Chandrasekaran, Sowrirajan; Sudha, Natesan; Premnath, D; Enoch, Israel V M V

    2015-09-01

    This work deals with the synthesis of 6-methyl-3-[(4'-methylphenyl)imino]methyl-4H-chromen-4-one (MMPIMC), its binding to β-cyclodextrin, and the influence of the cyclodextrin complexation on the compound's binding to bovine serum albumin (BSA). The 1:2 stoichiometry for the complexation of MMPIMC with β-cyclodextrin is determined with the binding constant of 1.90 × 10(4) M(-2). The structure of host-guest complex plays a role in protein binding of MMPIMC. One- and two-dimensional NMR spectra are used to determine the mode of binding of the guest to β-cyclodextrin cavity and the structure of the inclusion complex is proposed. The binding of MMPIMC with BSA in the absence and the presence of β-cyclodextrin is studied. The binding strengths of MMPIMC-BSA (1.73 × 10(5) M(-1)) and β-cyclodextrin-complexed MMPIMC-BSA (9.0 × 10(4) M(-1)) show difference in magnitude. The Förster Resonance Energy Transfer efficiency and the proximity of the donor and acceptor molecules, are modulated by β-cyclodextrin. Molecular modeling is used to optimize the sites and mode of binding of MMPIMC with bovine serum albumin.

  15. Aggregation property of glycyrrhizic acid and its interaction with cyclodextrins analyzed by dynamic light scattering, isothermal titration calorimetry, and NMR.

    PubMed

    Izutani, Yusuke; Kanaori, Kenji; Oda, Masayuki

    2014-06-17

    The structural properties of glycyrrhizic acid, a sweet-tasting constituent of Glycyrrhiza glabra, and its interaction with cyclodextrins were analyzed using dynamic light scattering, isothermal titration calorimetry, and NMR. The dynamic light scattering and NMR studies showed that glycyrrhizic acid forms a water-soluble aggregate that disperses upon the addition of γ-cyclodextrin. The high sweetness of glycyrrhizic acid can be closely correlated with this aggregation, because the multimers of glycyrrhizic acid can simultaneously bind to the sweet taste receptors on the human tongue. The isothermal titration calorimetry experiments demonstrated that γ-cyclodextrin binds to glycyrrhizic acid more strongly than β-cyclodextrin, however, both reactions are accompanied by a favorable change in binding entropy. Considering the large negative change in heat capacity that is observed during the binding of γ-cyclodextrin, the main driving force for the binding is hydrophobic interactions with dehydration, which is typical for inclusion complex. NMR experiments showed that γ-cyclodextrin interacts with the central part of the aglycone moiety, not the glucuronic acid moieties, resulting in high binding affinity. It should also be noted that the two distinct complexes of glycyrrhizic acid with γ-cyclodextrin would exist in aqueous solution.

  16. [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.

  17. Thionin in a cyclodextrin nanocavity: Measuring local compressibilities by pressure tuning hole burning spectroscopy

    NASA Astrophysics Data System (ADS)

    Hecht, Christoph; Hermann, Peter; Friedrich, Josef; Chang, Cheng-Chung; Chang, Ta-Chau

    2005-09-01

    We present pressure tuning hole burning experiments on thionin with α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) in a glycerol/water glass. The low temperature absorption spectra do not show the formation of a caging complex. The pressure tuning data, however, show that the compressibility of the sample with β-CD, where the formation of an inclusion complex is not restricted due to geometrical reasons increases as compared to the other samples. This is just the opposite of what one would expect. This increase is interpreted in terms of a reduced solvent density around the chromophore due to the hydrophobic effect.

  18. Differential time-series expression of immune-related genes of Pacific white shrimp Litopenaeus vannamei in response to dietary inclusion of beta-1,3-glucan.

    PubMed

    Wang, Yu-Chi; Chang, Poh-Shing; Chen, Houng-Yung

    2008-01-01

    Time-series changes in transcript abundance of nine genes encoding important immune proteins in haemocytes or hepatopancreas of Pacific white shrimp Litopenaeus vannamei fed daily in a 1-week feeding trial diets containing three levels (0%, 0.2% or 1%) of beta-1,3-glucan from Schizophyllum commune were quantified by real-time PCR. As a whole, the immune modulation elicited by beta-glucan is bimodal, one swift reaction of up- or down-regulation occurred within 24h and a delayed regulation was commenced as late as 3-7days. Haemocyanin, crustin, prophenoloxidase (proPO) and transglutaminase (TGase) did not respond to the glucan treatment. While penaeidin 3 (Litvan PEN3) was swiftly down-regulated (0-24h), lysozyme and cytosolic manganese superoxide dismutase (cMnSOD) were swiftly up-regulated (0-24h). In contrast, the two pattern recognition proteins (PRPs), beta-glucan binding protein-high density lipoprotein (BGBP-HDL) and lipopolysaccharide/beta-glucan binding protein (LGBP), showed a delayed up-regulation. Their expressions were not maximized until as late as 72h or 7days, respectively, which coincide with the initiation of reported immune enhancement (6-24days) of PO and SOD activity, phagocytosis and superoxide anion production in penaeid shrimp receiving glucan-containing diet. These immune responses could be the downstream effects of the two PRP gene up-regulation that predispose the shrimp to a state of high immune responsiveness. Increased dosage of beta-glucan from 2 to 10gkg(-1) diet did not affect the expressions of the genes, indicating the sufficiency of beta-glucan supplementation at 2gkg(-1) diet.

  19. Rheological and structural characterization of the interactions between cyclodextrin compounds and hydrophobically modified alginate.

    PubMed

    Burckbuchler, Virginie; Kjøniksen, Anna-Lena; Galant, Céline; Lund, Reidar; Amiel, Catherine; Knudsen, Kenneth D; Nyström, Bo

    2006-06-01

    Interactions in semidilute solutions of a hydrophobically modified alginate (HM-alginate) in the presence of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) monomer or a beta-cyclodextrin polymer (poly(beta-CD)) have been characterized at different temperatures with the aid of rheology and small-angle neutron scattering (SANS). The viscosity results for the HM-alginate/HP-beta-CD system reveal progressive deactivation of the hydrophobic associations as the concentration of HP-beta-CD increases. For the HM-alginate/poly(beta-CD) system, on the other hand, addition of poly(beta-CD) sets up bridges between adjacent polymer chains and thereby strengthens the associative network. A novel shear-thickening effect is observed at fairly high shear rates for the HM-alginate/poly(beta-CD) system, and this feature is influenced by temperature. Elevated temperature induces higher chain mobility and the formation of weaker network associations. Analyses of the SANS data disclosed that the association strength in HM-alginate/poly(beta-CD) mixtures increases strongly with increasing cosolute concentration, whereas no effect or a moderate weakening of the strength can be traced in HM-alginate/HP-beta-CD solutions upon addition of HP-beta-CD. The value of the correlation length xi is virtually not affected by the addition of cosolute for the HM-alginate/poly(beta-CD) system, whereas the decoupling of hydrophobic moieties of the polymer upon addition of HP-beta-CD gives rise to a smaller value of xi, suggesting that the size of the heterogeneity patches is reduced. The SANS results suggest that compact association structures are formed in the HM-alginate/poly(beta-CD) solutions.

  20. Investigations of bisacodyl with modified β-cyclodextrins: Characterization, molecular modeling, and effect of PEG.

    PubMed

    Li, Shanshan; Wang, Lili; Jiang, Jian; Tang, Peixiao; Wang, Qing; Wu, Di; Li, Hui

    2015-12-10

    Bisacodyl inclusion into hydroxypropyl-β-cyclodextrin and 2,6-di-O-methyl-β-cyclodextrin cavities was experimentally and theoretically investigated, and the effect of PEG 4000 on these inclusions was studied. Isothermal calorimetry titration curves indicated that the binary inclusion processes are enthalpy- and entropy-driven. The solid-state complexes were fully characterized by FT-IR, XRPD, DSC and SEM analyses. FT-IR, (1)H NMR, and ROESY studies provided the most favorable encapsulation modes of binary complexes, and results were further confirmed by molecular docking and molecular dynamics studies. The presence of PEG 4000 slightly enhanced encapsulation efficiency, solubility and dissolution rates of the binary complexes. In vivo studies showed that complexes with CDs markedly accelerated gastrointestinal transit time compared with pure bisacodyl, whereas addition of PEG 4000 showed no further significant improvement of the bioavailability.

  1. Host-Guest Strategy to Reversibly Control a Chloride Carrier Process with Cyclodextrins.

    PubMed

    Gravel, Julien; Kempf, Julie; Schmitzer, Andreea

    2015-12-14

    Herein, we report a reversible modular chloride transport process based on host-guest competitive interactions between an imidazolium-based chloride carrier and beta-cyclodextrin. We report evidence for the formation of the supramolecular complex between 1,3-bis(2-(adamantan-1-yl)ethyl)imidazolium bis(trifluorometyl-sulfonyl)imide with two β-cyclodextrins. Through fluorescence assays in liposomes and black lipid membrane experiments, we demonstrate that the formation of the supramolecular complex results in the inhibition of the chloride transport. We show that the chloride transport process can be entirely restored in the presence of competitive adamantyl-functionalized guests. This is the first example of an entirely reversible modular chloride transport process in phospholipid bilayers involving a mobile carrier transporter and cyclodextrin supramolecular complex.

  2. Study on the supramolecular system of meso-tetrakis (4-sulfonatophenyl) porphyrin and cyclodextrins by spectroscopy

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-ping; Pan, Jing-hao; Shuang, Shao-min

    2001-12-01

    The ability of β-cyclodextrin (β-CD), sulfurbutylether-β-CD (SBE-β-CD) and hydroxypropyl-β-CD (HP-β-CD) to break the aggregate of the meso-Tetrakis (4-sulfonatophenyl) porphyrin (TPPS 4) and to form 2:1 inclusion complexes has been studied by adsorption and fluorescence spectroscopy. The formation constants are calculated, respectively by fluoremetry, from which the inclusion capacity of different CDs is compared and the inclusion mechanism of charged-β-CD (SBE-β-CD) is quite different from that of parent β-CD. At lower pH, the complexation between HP-β-CD and H 2TPPS 42+ (the form of the diprotonated TPPS 4) hampers the continuous protonation of the pyrrole nitrogen of TPPS 4 and the hydrophobic cavity may prefer to bind an apolar neutral porphyrin molecule. 1HNMR data support the inclusion conformation of the porphyrin-cyclodextrin supramolecular system, indicating the interaction of meso-phenyl groups of TPPS 4 with the cavity of CDs. For this host-guest inclusion model, cyclodextrin, being regarded as the protein component, which acts as a carrier enveloping the active site of heme prosthetic group within its hydrophobic environment, provides a protective sheath for porphyrin, creating artificial analogues of heme-containing proteins. However, the TPPS 4, encapsulated within this saccharide-coated barrier, its physico-chemical, photophysical and photochemical properties changed strongly.

  3. Free volumes studies in Thymoquinone and Carvone β-cyclodextrin nanoparticles by positron annihilation lifetime spectroscopy

    NASA Astrophysics Data System (ADS)

    Ferreira Marques, M. F.; Gordo, P. M.; Moreira da Silva, A.

    2013-06-01

    Positron annihilation lifetime spectroscopy is used to study free volume in β-cyclodextrin with the encapsulation of thymoquinone and S-carvone, in samples covering the guest to host fraction range from 1:0.1 to 1:1. The results clearly indicate the presence of long lifetime components related to Ps-formation. Although the behavior of the two guests is different, in both cases the results indicate the formation of 1:1 cyclodextrin inclusion compounds. Data show that the addition of carvone to β-cyclodextrin results in a decrease of the o-Ps lifetime corresponding to a reduction of the average radius of cavities from 2.41 Å to 2.29 Å, whereas the addition of thymoquine decreases the radius from 2.57 Å to 2.35 Å. In turn, the intensity varied from 20.55 to 19.20% and from 20.83 to 0.41%, respectively.

  4. Refolding of detergent-denatured lysozyme using β-cyclodextrin-assisted ion exchange chromatography.

    PubMed

    Zhang, Li; Zhang, Qinming; Wang, Chaozhan

    2013-03-01

    Chromatography-based protein refolding is widely used. Detergent is increasingly used for protein solubilization from inclusion bodies. Therefore, it is necessary to develop a refolding method for detergent-denatured/solubilized proteins based on liquid chromatography. In the present work, sarkosyl-denatured/dithiothreitol-reduced lysozyme was used as a model, and a refolding method based on ion exchange chromatography, assisted by β-cyclodextrin, was developed for refolding detergent-denatured proteins. Many factors affecting the refolding, such as concentration of urea, concentration of β-cyclodextrin, pH and flow rate of mobile phases, were investigated to optimize the refolding conditions for sarkosyl-denatured lysozymes. The results showed that the sarkosyl-denatured lysozyme could be successfully refolded using β-cyclodextrin-assisted ion exchange chromatography.

  5. Effect of pH on the complexation of kaempferol-4'-glucoside with three β-cyclodextrin derivatives: isothermal titration calorimetry and spectroscopy study.

    PubMed

    Zheng, Yan; Dong, Li-Na; Liu, Min; Chen, Aiju; Feng, Shangcai; Wang, Bingquan; Sun, Dezhi

    2014-01-08

    The utilization of kaempferol and its glycosides in food and pharmaceutical industries could be improved by the formation of inclusion complexes with cyclodextrins at different pH. This study explores the complexation of kaempferol-4'-glucoside with sulfobutyl ether-β-cyclodextrin (SBE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), and methylated-β-cyclodextrin (M-β-CD) in phosphate buffer solutions of different pH using isothermal titration calorimetry, UV-vis absorption and proton nuclear magnetic resonance spectroscopy at 298.2 K. Experimental results showed that kaempferol-4'-glucoside binds with the three β- cyclodextrins in the same 1:1 stoichiometry. The rank order of stability constants is SBE-β-CD > HP-β-CD > M-β-CD at the same pH level and pH 6.0 > pH 7.4 > pH 9.0 for the same cyclodextrin. The binding of kaempferol-4'-glucoside with the three β-cyclodextrin derivatives is synergistically driven by enthalpy and entropy at pH 6.0 and enthalpy-driven at pH 7.4 and 9.0. The possible inclusion mode was that in the cavity of β-CD is included the planar benzopyranic-4-one part of the kaempferol-4'-glucoside.

  6. 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

  7. Self-assembly of cyclodextrin complexes: effect of temperature, agitation and media composition on aggregation.

    PubMed

    Messner, Martin; Kurkov, Sergey V; Maraver Palazón, Marta; Álvarez Fernández, Berta; Brewster, Marcus E; Loftsson, Thorsteinn

    2011-10-31

    Recently it has been shown that aggregation of drug/cyclodextrin inclusion complexes is strongly influenced by the drug molecule in addition to self-assembling tendencies of the cyclodextrin itself in aqueous media. Whereas the mechanistic basis of cyclodextrin self-assembly is known, the driving forces for complex aggregation are still unknown. In the present study, the influence of temperature on hydrocortisone/2-hydroxypropyl-β-cyclodextrin complex aggregation is investigated as are influences associated with the addition of ethanol or water soluble polymers to the aqueous systems. Furthermore the effect of stirring on the aggregation is assessed. Size exclusion permeability studies were conducted to estimate complex aggregation tendencies. The results indicate that self-assembled complex aggregates are metastable and notably become smaller with increasing temperature and the addition of ethanol. Water soluble polymers also reduce the size of the complex aggregates. Specifically, hexadimethrine bromide had the greatest impact, since addition of this compound eliminated aggregates from the systems or reduced their size below the molecular weight cut-off of the sizing membrane (8 kDa). Similar observations are made when aqueous solutions of hydrocortisone and 2-hydroxypropyl-β-cyclodextrin are equilibrated by stirred.

  8. Microwave synthesis and in vitro stability of diclofenac-β-cyclodextrin conjugate for colon delivery.

    PubMed

    Vieira, Amélia C F; Serra, Arménio C; Carvalho, Rui A; Gonsalves, Alexandra; Figueiras, Ana; Veiga, Francisco J; Basit, Abdul W; Rocha Gonsalves, António M d'A

    2013-04-02

    The aim of this work was to synthesize an ester prodrug of diclofenac and β-cyclodextrin suitable for colonic delivery. The synthesis of an ester linkage between diclofenac and β-cyclodextrin was conducted by the nucleophilic substitution of mono-6-tosyl-β-cyclodextrin under microwaves irradiation. After purification, the conjugate was characterized by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry; infrared (IR) spectroscopy; proton nuclear magnetic resonance ((1)H NMR) spectroscopy; and two-dimensional rotating frame nuclear overhauser effect (ROESY) spectroscopy. The purity was qualified by high pressure liquid chromatography (HPLC). To assess its potential for colonic delivery, the conjugate was evaluated for stability in simulated gastric and small intestinal fluids, and in fecal material from humans processed within a slurry under anaerobic conditions. The conjugate was successfully synthesized with a yield of 20% following purification. The mass spectra showed the parent peak m/z 1434 corresponding to [conjugate+Na] adduct. IR and NMR results confirmed that the carboxyl group of diclofenac is covalently bound to one of the hydroxyl groups of cyclodextrin by an ester linkage. Moreover, ROESY data indicated that the formation of the conjugate is not accompanied by the inclusion of diclofenac within the cyclodextrin. The conjugate was otherwise stable in simulated gastric and small intestinal conditions, but was also readily hydrolyzed liberating diclofenac in less than 2h within the human fecal slurry. This confirmed the potential for this new prodrug as a carrier for colonic delivery.

  9. 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.

  10. 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

  11. Enhanced biodegradation of transformer oil in soils with cyclodextrin--from the laboratory to the field.

    PubMed

    Molnár, Mónika; Leitgib, Laura; Gruiz, Katalin; Fenyvesi, Eva; Szaniszló, Nikoletta; Szejtli, József; Fava, Fabio

    2005-03-01

    The use cyclodextrins for the intensification of bioremediation by improving the mobility and bioavailability of contaminants has recently been studied. In this work, the role of randomly methylated beta-cyclodextrin in the bioremediation of soils contaminated with transformer oil was studied both in bench scale bioreactors and through field experiments. The aims of this research were to (a) establish the scientific background of a cyclodextrin-based soil bioremediation technology, (b) demonstrate its feasibility and effectiveness in the field, and (c) develop an integrated methodology, consisting of a combination of physical, chemical, biological and ecotoxicological analytical methods, for efficiently monitoring the technology performances. The stepwise increasing scale of the experiments and the application of the integrated analytical methodology supported the development of a scientifically established new technology and the identification of the advantages and the limitations of its application in the field. At each phase of the study, randomly methylated beta-cyclodextrin was found to significantly enhance the bioremediation and detoxification of the transformer oil-contaminated soils employed by increasing the bioavailability of the pollutants and the activity of indigenous microorganisms.

  12. Nano-Assemblies of Modified Cyclodextrins and Their Complexes with Guest Molecules: Incorporation in Nanostructured Membranes and Amphiphile Nanoarchitectonics Design

    PubMed Central

    Zerkoune, Leïla; Angelova, Angelina; Lesieur, Sylviane

    2014-01-01

    A variety of cyclodextrin-based molecular structures, with substitutions of either primary or secondary faces of the natural oligosaccharide macrocycles of α-, β-, or γ-cyclodextrins, have been designed towards innovative applications of self-assembled cyclodextrin nanomaterials. Amphiphilic cyclodextrins have been obtained by chemical or enzymatic modifications of their macrocycles using phospholipidyl, peptidolipidyl, cholesteryl, and oligo(ethylene oxide) anchors as well as variable numbers of grafted hydrophobic hydrocarbon or fluorinated chains. These novel compounds may self-assemble in an aqueous medium into different types of supramolecular nanoassemblies (vesicles, micelles, nanorods, nanospheres, and other kinds of nanoparticles and liquid crystalline structures). This review discusses the supramolecular nanoarchitectures, which can be formed by amphiphilic cyclodextrin derivatives in mixtures with other molecules (phospholipids, surfactants, and olygonucleotides). Biomedical applications are foreseen for nanoencapsulation of drug molecules in the hydrophobic interchain volumes and nanocavities of the amphiphilic cyclodextrins (serving as drug carriers or pharmaceutical excipients), anticancer phototherapy, gene delivery, as well as for protection of instable active ingredients through inclusion complexation in nanostructured media.

  13. Using reversed phase high performance liquid chromatography to study the complexation of anthocyanins with β-cyclodextrin

    NASA Astrophysics Data System (ADS)

    Deineka, V. I.; Lapshova, M. S.; Deineka, L. A.

    2014-06-01

    It is shown by means of reversed phase high performance liquid chromatography (RP HPLC) with mobile phases containing additions of β-cyclodextrin that 5-glucosides of cyanidin and pelargonidin form stronger inclusion complexes than 3-glucosides; this is explained by the steric interference of the glucoside radical.

  14. 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.

  15. Interactions between cyclodextrins and cellular components: Towards greener medical applications?

    PubMed Central

    2016-01-01

    In the field of host–guest chemistry, some of the most widely used hosts are probably cyclodextrins (CDs). As CDs are able to increase the water solubility of numerous drugs by inclusion into their hydrophobic cavity, they have been widespread used to develop numerous pharmaceutical formulations. Nevertheless, CDs are also able to interact with endogenous substances that originate from an organism, tissue or cell. These interactions can be useful for a vast array of topics including cholesterol manipulation, treatment of Alzheimer’s disease, control of pathogens, etc. In addition, the use of natural CDs offers the great advantage of avoiding or reducing the use of common petroleum-sourced drugs. In this paper, the general features and applications of CDs have been reviewed as well as their interactions with isolated biomolecules leading to the formation of inclusion or exclusion complexes. Finally, some potential medical applications are highlighted throughout several examples. PMID:28144335

  16. Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins.

    PubMed

    Kfoury, Miriana; Lounès-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2016-04-01

    Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability.

  17. Effect of cyclodextrins and pH on the permeation of tetracaine: supramolecular assemblies and release behavior.

    PubMed

    Teixeira, Raquel S; Veiga, Francisco J B; Oliveira, Rita S; Jones, Stuart A; Silva, Sérgio M C; Carvalho, Rui A; Valente, Artur J M

    2014-05-15

    This work provides a new insight on fundamental principles of the interaction mechanism between two forms of tetracaine - a potent local anesthetic - both in neutral (TC) and ionized (TC(+)) states, with beta- (β-CD) and hydroxypropyl-beta-cyclodextrin (HP-β-CD), and how such interactions affect the transport of tetracaine, at different concentrations, across a model membrane. The kinetics and mechanism of TC release from HPMC gels is also evaluated giving an insight on the role of cyclodextrin on the tetracaine transport. HPLC, fluorescence and NMR spectroscopies provided solid physicochemical knowledge of these systems and in vitro studies were performed to obtain relevant data on the transport and mechanism parameters. HPLC and fluorescence spectroscopy data revealed that tetracaine interacts with both cyclodextrins on a 1:1 stoichiometry but it is observed that neutral tetracaine forms more stables complexes (ca. 1050 M(-1) for both cyclodextrins) than in its ionized form (628 and 337 M(-1) for β-CD and HP-β-CD respectively). Despite of that, no host-guest interactions take place as seen by ROESY. This study clearly demonstrates that both forms of tetracaine are successfully released from the formulations at a controlled rate, following a Super-Case transport mechanism and the transport of tetracaine can be tuned by using cyclodextrins.

  18. Sulfoalkyl ether-alkyl ether cyclodextrin derivatives, their synthesis, NMR characterization, and binding of 6alpha-methylprednisolone.

    PubMed

    Tongiani, Serena; Velde, David Vander; Ozeki, Tetsuya; Stella, Valentino J

    2005-11-01

    The objective of this study is to see if random alkyl ethers of various sulfoalkyl ether cyclodextrins can be synthesized and characterized. The purpose of the alkylation was to test the hypothesis that an increase in the "height" of a cyclodextrins cavity would help in the binding/complexation of larger more structurally complex molecules. The synthesis of new cyclodextrin derivatives comprising a mixture of sulfoalkyl ether and alkyl ether substituents on the same cyclodextrin ring was performed in aqueous alkaline solutions using various sultones and alkylsulfates. The method presented provided an easy and efficient way to modify cyclodextrins avoiding the use of organic solvents and high quantities of alkylating agents and could be carried out in either a two step or "one pot" single step process. Purification was by neutralization followed by ultrafiltration. The derivatives were characterized by 1D, ((1)H and (13)C), and a 2D NMR technique (HMQC, Heteronuclear Multiple Quantum Coherence). The combination of these techniques allowed an analysis of the degree of substitution and the site of substitution on the cyclodextrin (CD) nucleus. For both beta- and gamma-CD, sulfoakylation was preferred on the 2 > 3 > 6 hydroxyls while alkylation was preferred 6 > 2 > 3. Due to the simultaneous presence of short alkyl ether chains and negatively charged sulfoalkyl ether chains, these mixed water-soluble cyclodextrin derivatives, especially those of gamma-cyclodextrin, should be able to bind more complex drugs. The improved binding capacity of these new modified CDs with the model drug 6alpha-methylprednisolone is reported.

  19. Pharmacokinetic study of solid-lipid-nanoparticles of altretamine complexed epichlorohydrin-β-cyclodextrin for enhanced solubility and oral bioavailability.

    PubMed

    Gidwani, Bina; Vyas, Amber

    2017-03-14

    Altretamine is a synthetic drug approved for treatment of ovarian cancer. The only drawback with its formulation is poor aqueous solubility and low oral bioavailability. In the present work an attempt has been made to prepare inclusion complex of altretamine with epi