Study on the inclusion interaction of ethyl violet with cyclodextrins by MWNTs/Nafion modified glassy carbon electrode

The interactions of ethyl violet (EV) with cyclodextrins (CDs) were investigated by Multi-wall carbon nanotubes/Nafion composite film modified glassy carbon electrode (MWNTs/Nafion/GCE). It was found that the MWNTs/Nafion composite film can effectively catalyze the electrode reaction of EV. The variation of the electrochemical behavior of EV upon the addition of CDs indicated the formation of the inclusion complexes of EV with β-CD, heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), heptakis (2,6-di-O-methyl)-β-CD (DM-β-CD), hydroxypropyl-β-CD (HP-β-CD), and carboxymethyl-β-CD (CM-β-CD). The stoichiometry ratios of EV and the above five CDs were found to be 1:1. The inclusion ability obeyed the order: CM-β-CD > HP-β-CD > TM-β-CD > DM-β-CD > β-CD. The results showed that the modified β-CDs exhibited stronger binding ability than native β-CD, especially the charged CM-β-CD, which implied that the inclusion capacity depends on not only size matching and hydrophobicity but also electrostatic interaction. ¹HNMR spectra and molecule mechanics calculations suggested that EV was included into the cavity of β-CD from the wider side.     

Investigation on Non-covalent Complexes of Cyclodextrins with Li+ in Gas Phase by Mass Spectrometry

To investigate the non-covalent interaction between cyclodextrins (CD) and lithium ion, a stoichiometry of α-CD, β-CD, heptakis(2,6-di-O-methyl)-β-CD (DM-β-CD), or heptakis(2,3,6-tri-O-methyl)-β-CD (TM-β-CD) was mixed with lithium salt, respectively, and then incubated at room temperature for 10 min to reach the equilibrium. In posi-tive mode, the electrospray ionization mass spectrometry (ESI-MS) results demonstrated that lithium ion can conjugate to α-, β-, DM-β- or TM-β-CD and form 1:1 stoichiometric non-covalent complexes. The binding of the complexes was further confirmed by collision-induced dissociation. The dissociation constants K_d1 of four complexes (Li+α-CD, Li+β-CD, Li+DM-β-CD, and Li+TM-β-CD) were determined by mass spectrometric titration. The results showed K_d1 were 18.7, 26.7, 33.6, 30.5 μmol/L for the complexes of Li+ with α-CD, β-CD, DM-β-CD, and TM-β-CD, respectively. K_d1 for the Li⁺ complexes of β-CD is smaller than that of DM-β-CD due to its steric effect of the partial substituted -CH₃. The Kd1 for the Li⁺ complexes of DM-β-CD is nearly in agreement with that of TM-β-CD, indicating Li⁺ is more likely to locate in the small rim of DM-β-CD's hydrophobic cavity. The DFT results showed through electrostatic interaction, one Li+ can strongly conjugate to four neighboring oxygen atoms. For the (α-CD+Li)⁺ complex, one Li⁺ may also situate the small rim of α-CD's hydrophobic cavity to form a non-specific host-guest complex.     

Complexation of Ketoconazole by Native and Modified Cyclodextrins

Complexation of ketoconazole (KET), a broad-spectrum antifungal drug, with β- and γ-cyclodextrins (CDs), heptakis (2,6-di-O-methyl)-β-CD (2,6-DM-β-CD), heptakis (2,3,6-tri-O-methyl)-β-CD (TM-β-CD), 2-hydroxypropyl-β-CD (2HP-β-CD) and carboxymethyl-β-CD (CM-β-CD) was studied. The stability constants were determined by the solubility method at pH = 6 and for 2,6-DM-β-CD and CM-β-CD at pH = 5. At pH = 6, the stability constants increased in the order: TM-β-D < γ-CD < 2HP-β-CD < β-CD < CM-β-CD < 2,6-DM-β-CD. At pH = 5, due to the increased ionization of KET, the stability constant with CM-β-CD increased and with 2,6-DM-β-CD decreased. For complexes of KET with 2HP-β-CD and 2,6-DM-β-CD, the thermodynamic parameters of complexation were determined from the temperature dependence of the corresponding stability constants. For β–γ and TM-β-CD complexes, calculations using HyperChem 6 software by the Amber force field were carried out to gain some insight into the host–guest geometry.     

Host–guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Nitroheterocyclic compounds (NC) were candidate drugs proposed for Chagas disease chemotherapy. In this study, we investigated the complexation of hydroxymethylnitrofurazone (NFOH), a potential antichagasic compound, with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), Hydroxypropyl-β-cyclodextrin (HP-β-CD), Dimethyl-β-cyclodextrin (DM-β-CD) and γ-cyclodextrin (γ-CD) by fluorescence spectroscopy and molecular modeling studies. Hildebrand–Benesi equation was used to calculate the formation constants of NFOH with cyclodextrins based on the fluorescence differences in the CDs solution. The complexing capacity of NFOH with different CDs was compared through the results of association constant according to the following order: DM-β-CD > β-CD > α-CD > HP-β-CD > γ-CD. Molecular modeling studies give support for the experimental assignments, in favor of the formation of an inclusion complex between cyclodextrins with NFOH. This is an important study to investigate the effects of different kinds of cyclodextrins on the inclusion complex formation with NFOH and to better characterize a potential formulations to be used as therapeutic options for the oral treatment of Chagas disease.     

Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes

In the present study influence of nature of selected cyclodextrins (CDs) and of methods of preparation of drug–CD complexes on the oral bioavailability, in vitro dissolution studies and pharmacodynamic activity of a sparingly water soluble drug rosuvastatin (RVS) was investigated. Phase solubility studies were conducted to find the interaction of RVS with β-CD and its derivatives, which indicated the formation of 1:1 stoichiometric inclusion complex. The apparent stability constant (K_1:1) calculated from phase solubility diagram were in the rank order of β-CD < hydroxypropyl-β-cyclodextrin (HP-β-CD) < randomly methylated-β-cyclodextrin (RM-β-CD). Equimolar drug–CD solid complexes prepared by different methods were characterized by the Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). FTIR study demonstrated the presence of intermolecular hydrogen bonds and ordering of the molecule between RVS and CDs in inclusion complexes. DSC and XRD analysis confirmed formation of inclusion complex by freeze dried method with HP-β-CD and RM-β-CD. Aqueous solubility and dissolution studies indicated improved dissolution rates of prepared complexes in comparison with drug alone. Moreover, CD complexes demonstrated of significant improvement in reducing total cholesterol and triglycerides levels as compared to pure drug. However the in vivo results only partially agreed with those obtained from phase solubility studies.     

NMR spectroscopic characterization of inclusion complexes of hydroxy-substituted naphthalenes with native and modified β-cyclodextrins

The equilibrium constants (K) for the inclusion complexation of three kinds of β-cyclodextrins (β-CDs: native β-CD, heptakis(2,6-di-O-methyl)-β-CD, and 6-O-α-d-glucosyl-β-CD) with OH-substituted naphthalenes (2-naphthol, 2,3-dihydroxynaphthalene, and 2,6-dihydroxynaphthalene) were determined from the induced chemical shifts of NMR measurements for inclusion complexes: K = 188–1,250 mol^?1 dm³. The modified β-CDs form stable 1:1 inclusion complexes with OH-substituted naphthalenes, and the high stability of inclusion complexes of 2,6-dihydroxynaphthalene having a hydrophobic body and hydrophilic ends is shown. In addition, the structures of inclusion complexes were characterized by 2D ROESY NMR measurements. The differences in the structure of the inclusion complexes were observed for three kinds of naphthol guest molecules. Based on the results, the inclusion abilities enhanced by methylation of the OH groups at the CD rim or the side chain of branched β-CD are discussed.     

Study on the Supramolecular System of TAPP and Cyclodextrins by Spectroscopy

The ability of β-cyclodextrin (β-CD), γ-CD, hydroxypropyl-β-CD (HP-β-CD), trimethyl-β-CD (TM-β-CD), sulfurbutylether-β-CD (SBE-β-CD) and carboxymethyl-β-cyclodextrin (CM-β-CD) to break the aggregate of the meso-tetrakis(4-N-trimethylaminobenzyl)porphyrin (TAPP) and to form 2:1 inclusion complexes has been studied by absorption and fluorescence spectroscopy. The formation constants are calculated, respectively, by fluorimetry, from which the inclusion capacity of different CDs is compared and the inclusion mechanism of charged-β-CD (SBE-β-CD and CM-β-CD) is quite different from that of the parent β-CD. At lower pH, the complexation between TM-β-CD and H²TAPP²⁺ (the form of the diprotonated TAPP) hampers the continuous protonation of the pyrrole nitrogen of TAPP 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 the meso-phenyl groups of TAPP 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 the porphyrin, creating artificial analogues of heme-containing proteins. However, for TAPP, encapsulated within this saccharide-coated barrier, its photophysical and photochemical properties changed strongly.     

Spectroscopic characterisation of the inclusion complexes between the antifungal drugs naftifine and terbinafine and cyclodextrins

The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investigated by UV/visible and ¹H NMR spectroscopy, ROESY techniques and also ESI-MS. Both drugs form 1:1 inclusion complexes with all the CDs tested except with α-CD, as deduced from the Benesi–Hildebrand plots and confirmed by ESI-MS and NMR spectroscopy (Job plot method). The K ₁₁ values for NF decrease in the order β-CD > methylated β-CD > 2-hydroxypropyl-β-CD >γ-CD. The determination of the enthalpy and entropy provides information about the main driving forces in the process. The stability constants of the complexes NF–β-CD, TB–β-CD and TB–γ-CD determined by ¹H NMR spectroscopy are in agreement with the values obtained by UV. For TB–β-CD, the value is higher, due to the fact that the length of the TB aliphatic chain allows a deeper inclusion of the naphthalene group inside the corresponding β-CD molecule, according to the 2D ROESY experiments.     

Complexation of triptolide and its succinate derivative with cyclodextrins: affinity capillary electrophoresis, isothermal titration calorimetry and 1H NMR studies

The complexation of the triptolide PG490 and its succinate derivative PG490-88Na with various cyclodextrins was studied using three complementary techniques: affinity capillary electrophoresis (ACE), isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). The apparent binding constants of the complexes formed between the drugs and 8 CDs (α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD, HP-γ-CD, CM-β-CD and amino-β-CD) were determined by ACE through linear Scott's plots. The apparent and averaged binding constants of the complexes formed between PG490-88 and β-CD, γ-CD, HP-α-CD, HP-β-CD or HP-γ-CD are contained in the narrow range 135-167 M(-1). For the anionic CM-β-CD and cationic amino-β-CD, these constants are 38 and 278 M(-1), respectively, which is in accordance with electrostatic repulsions or attractions with the succinate moiety. ITC and NMR investigations for the binding constants determinations were performed for 2 CDs allowing high complexation: HP-β-CD and amino-β-CD. The three techniques provided similar results. ITC and NMR, in contrast to ACE, allowed to study the complexes formed between the neutral compound PG490 and neutral cyclodextrins. A more advanced characterization of the PG 490-88Na/amino-β-CD complex, which displays the highest apparent binding constant, was undertaken using NMR spectroscopy. The 1:1 stoichiometry of the complex was established by (1)H NMR 1D and selective 1D TOCSY experiments using the continuous variation method. Moreover, the 1D and 2D ROESY experiments revealed the inclusion of the isopropyl moiety of the triptolide derivative in the hydrophobic CD cavity. Altogether, the data provide strong evidences that the two triptolide compounds can be efficiently complexed with CD.     

Inclusion complexes of cyclodextrins with 4-amino-1,8-naphthalimides (part 2)

Fluorescence spectroscopy was used to characterize inclusion compounds between 4-amino-1,8-naphthalimides (ANI) derivatives and different cyclodextrins (CDs). The ANI derivatives employed were N-(12-aminododecyl)-4-amino-1,8-naphthalimide (mono-C₁₂ANI) and N,N′-(1,12-dodecanediyl)bis-4-amino-1,8-naphthalimide (bis-C₁₂ANI). The CDs used here were α-CD, β-CD, γ-CD, HP-α-CD, HP-β-CD and HP-γ-CD. The presence of CDs resulted in pronounced blue-shifts in the emission spectra of the ANI derivatives, with increases in emission intensity. This behavior was parallel to that observed for the dyes in apolar solvents, indicating that inclusion complexes were formed between the ANI and the CDs. Mono-C₁₂ANI formed inclusion complexes of 1:1 stoichiometry with all the CDs studied. Complexes with the larger CDs (HP-β-CD, HP-γ-CD and γ-CD) were formed by inclusion of the chromophoric ANI ring system, whereas the smaller CDs (α-CD, HP-α-CD and β-CD) formed complexes with mono-C₁₂ANI by inclusion of the dodecyl chain. Bis-C₁₂ANI formed inclusion complexes of 1:2 stoichiometry with HP-β-CD, HP-γ-CD and γ-CD, but did not form inclusion complexes with α-CD, HP-α-CD and β-CD. The data were treated in the case of the large CDs using a Benesi-Hildebrand like equation, giving the following equilibrium constants: mono-C₁₂ANI:HP-β-CD (K ₁₁ = 50 M^?1), mono-C₁₂ANI:HP-γ-CD (K ₁₁ = 180 M^?1), bis-C₁₂ANI:HP-β-CD (K ₁₂ = 146 M^?2), bis-C₁₂ANI:HP-γ-CD (K ₁₂ = 280 M^?2).     

Inclusion complexes of modified cyclodextrins with some flavonols

The inclusion complexes of four flavonols with modified cyclodextrins (CDs) have been investigated. The effect of heptakis (2,6-di-O-methyl) β-cyclodextrin (DM-β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility of flavonols, namely, galangin, kaempferol, quercetin, and myricetin was investigated, respectively. The increased solubility of all flavonols in the presence of CD was evidenced. The NMR experiment and molecular modeling studies showed that flavonols interact with each modified CD through different binding modes. Flavonols can complex with CDs largely by two binding modes. The first one is that B-ring of flavonols is oriented toward secondary rim of CD. The second one is that A-ring of flavonols is oriented toward secondary rim of CD. Whereas only the first mode was observed in DM-β-CD complexes, both the first and the second mode were observed in HP-β-CD complexes in this study.     

Complexation of tyrosol with cyclodextrins

Tyrosol (TY), 4-(2-hydroxyethyl)phenol, is an olive oil biophenol with antioxidant activity and positive effects on human health. This study has investigated the interactions of TY with cyclodextrins (CD) and a CD polymer. Complexation of TY with β-CD, hydroxypropyl-β-CD (HP-β-CD), and methyl-β-CD (Me-β-CD) has been evaluated both in aqueous solution and in the solid state. The techniques employed in solution to determine the apparent stability constants of the respective complexes were fluorescence and UV–visible spectroscopies. Complexation with β-CD and its derivatives involved an increase of both the UV absorbance and the intrinsic fluorescence of TY; a bathochromic shift of the UV spectrum was detected as well. The apparent stability constants obtained with native β-CD, Me-β-CD and HP-β-CD presented similar values. Complexes in the solid state were obtained by coevaporation and kneading. They were characterised by X-ray diffraction analysis and differential thermal analysis. The interaction of TY with β-CD led to a crystalline complex; the same diffraction pattern was obtained by coevaporation and kneading. The complexes obtained with methyl- and HP-β-CD were amorphous irrespective of the preparation method. In addition, the retention of TY in an insoluble polymer of CD crosslinked with epichlorohydrin has been quantified. In approximately 20 min, 1 mg of TY per gram of polymer was retained.     

Study on the complexation of isoquercitrin with β-cyclodextrin and its derivatives by spectroscopy

The inclusion complexes of isoquercitrin (IQ) with cyclodextrins (CDs) including β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and dimethyl-β-cyclodextrin (DM-β-CD) have been investigated using the methods of steady-state fluorescence, UV-vis absorption and induced circular dichroism. The stoichiometric ratio of the three complexes was found to be 1:1 and the stability constants (K) were estimated from spectrofluorometric titrations, as well as the thermodynamic parameters. Maximum inclusion ability was measured in the case of DM-β-CD due to the increased hydrophobicity of the host cavity, followed by HP-β-CD and β-CD. The effect of pH on the complexation process was also quantitatively assessed. IQ exists in different molecular forms depending on pH and β-CDs were most suitable for inclusion of the neutral form of IQ. The phase-solubility diagrams obtained with β-CD, HP-β-CD and DM-β-CD were all classical A_L type. And DM-β-CD provided the best solubility enhancement, 12.3-fold increase compared to 2.8- and 7.5-fold increase for β-CD and HP-β-CD. The apparent stability constants obtained from the solubility data at 25 °C were comparable with those obtained from the fluorescence assays. Moreover, ¹H NMR was carried out, which revealed that the IQ favorably inserted into the inner cavity from the chromone part instead of the phenyl part, which was in agreement with molecular modeling studies.     

NMR studies of interactions of new CB2 cannabinoid receptor ligands with cyclodextrins hosts. Correlation with micellar electrokinetic chromatography and reversed phase high performance liquid chromatography

Three selective CB₂ cannabinoid receptor ligands have recently been discovered to be promising anti-inflammatory agents but their low water solubility hinder their per os administration. The popularity of the cyclodextrins, from a pharmaceutical standpoint lies on their ability to interact with poorly water-soluble drugs and improve their solubility. Herein, three experimental approaches for calculating the stability constant of complexes between the selective CB₂ ligands and either the β-CD or the HP-β-CD, were tested: nuclear magnetic resonance, micellar electrokinetic chromatography and high performance liquid chromatography in reversed phase. In NMR studies the calculated K values were relatively high and were between 1486 and 3571 M^?1 with β-CD. With HP-β-CD they were between 1203 and 2650 M^?1. Concerning the two others techniques the K values were found lower. In MECK studies with β-CD they were between 308 and 792 M^?1 and with HP-β-CD between 124 and 764 M^?1. Finally in RP-HPLC studies with β-CD, they were between 539 and 1144 M^?1 and with HP-β-CD between 196 and 396 M^?1. These calculated constants suggest that a complexation phenomenon occurs. A model for inclusion of one of the CB₂ ligands in the β-CD was then proposed from molecular modeling studies.     

Investigation of indole chalcones encapsulation in β-cyclodextrin: determination of stoichiometry,binding constants and thermodynamic parameters

The study focuses on the formation of inclusion complexes of indole chalcone (IC) derivatives with β-cyclodextrin (β-CD), which involves absorption and steady state fluorescence spectroscopies. The formation of inclusion complexes is validated by increase in their absorbance and fluorescence intensity as well as the blue shift with increase in the concentration of β-CD in the aqueous solution. The stoichiometries and binding constants (K_in) of these complexes have been investigated by monitoring their absorbance and fluorescence spectral profiles. The data are analyzed by Benesi–Hildebrand plots as well as Job’s method, which indicate 1:1 stoichiometry of IC:β-CD complexes. Fluorescence measurements are also used to investigate the effect of temperature on the stability of inclusion complexes. Stability of IC:β-CD complexes is significantly affected with variation in substituents on the phenyl ring and temperature. It is observed that the stability of the inclusion complex decreases with increase in temperature; K_in(293 K)?>?K_in(298 K)?>?K_in(308 K)?>?K_in(318 K). All the experimental results and the geometrical data obtained using PM3 semiempirical method illustrate the partial inclusion of IC derivatives from the phenyl ring side in β-CD cavity. The binding process of IC derivatives with β-CD is found to be exothermic in nature and seems to be controlled by electrostatic and hydrophobic forces. The binding free energies calculated using semiemprical PM3 method for IC:β-CD complexes are found to be in the order: I?<?OH–I?<?Me–I?<?OMe–I?<?NH₂–I, which largely supports the findings based on the experimental binding constants.     

Simultaneous Chiral Separation of Geometry Isomers and Enantiomers of Nateglinide by Capillary Electrophoresis with Mixture of CD Derivations as Chiral Selector

Abstract

A capillary electrophoresis (CE) method for the simultaneous separation of geometry isomers and enantiomers of nateglinide was built. Several different dyclodextrin (CD) derivatives were tested for the chiral separation of nateglinide, and it was proved that ionic CDs [i.e., carboxymethy-β-CD (CM-β-CD) and sulphonic-β-CD (S-β-CD)] could show better chiral selectivity for both geometry isomers and enantiomers than the neutral CDs. The separation of geometry of both isomers and enantiomers of nateglinide was obtained by CE in a 75-µm i.d. × 60 cm (effective length 45 cm) fused-silica capillary at 11 kV voltage, while 30 mM phosphate (pH = 8.38) acted as running buffer and a mixture of 40 mM S-β-CD + 21 mM CM-β-CD served as chiral selector. The detective wavelength was set at 254 nm.     

Complex Formation of Hematoporphyrin with Cyclodextrins and 1,1′-Diheptyl-4,4′-bipyridinium Dibromide in Aqueous Solutions

At around 5×10^-6?mol?dm^-3 of hematoporphyrin (HP), an HP dimer exists as well as an HP monomer. The equilibrium constant for the dimerization of HP in pH 10.0 buffer has been evaluated to be 1.70×10⁵?mol^-1?dm³ from the HP concentration dependence of the absorption spectrum. In aqueous solution, HP forms 1:1 inclusion complexes with β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD). The fluorescence of HP is significantly enhanced by the addition of CDs. From simulations of the fluorescence intensity changes, the equilibrium constants for the formation of the CD–HP inclusion complexes have been estimated to be 200, 95.7, and 938?mol^-1?dm³ for β-CD, γ-CD, and TM-β-CD, respectively. HP forms a 1:1 complex with 1,1′-diheptyl-4,4′-bipyridinium dibromide (DHB) in aqueous solution. In contrast to the addition of CDs, the HP fluorescence is significantly quenched by the addition of DHB. The equilibrium constant for the formation of the HP–DHB complex has been evaluated to be 1.98×10⁵?mol^-1?dm³ from the fluorescence intensity change of HP. The addition of DHB to an HP solution containing β-CD induces a circular dichroism signal of negative sign, indicating the formation of a ternary inclusion complex involving β-CD, HP, and DHB. In contrast, there is no evidence for the formation of a ternary inclusion complex of HP with DHB and TM-β-CD.     

β-Cyclodextrin derivatives hybrid Fe3O4 magnetic nanoparticles as the drug delivery for ketoprofen

β-Cyclodextrin (β-CD) and its derivatives carboxymethyl-β-CD (CM-β-CD) and 2,6-dimethyl-β-CD (DM-β-CD) modified magnetic nanoparticles (CD-MNPs) were synthesized via layer-by-layer method. CDs grafted onto Fe₃O₄ MNPs were demonstrated by transmission electron microscopy, Fourier transform infrared and Zeta potential. Magnetic properties of CM-β-CD-MNPs, DM-β-CD-MNPs and β-CD-MNPs were characterized by vibrating sample magnetometer and the magnetic saturation values were 47, 46 and 44 emu g^?1, respectively. CD-MNPs as drug carriers were investigated by inclusion behavior and in vitro release using ketoprofen (KP) as a model drug. The maximum adsorption quantities of CM-β-CD-MNPs, DM-β-CD-MNPs and β-CD-MNPs for KP were 37.03, 7.63 and 25.12 mg g^?1, respectively, and the loading behaviors followed the Langmuir adsorption isotherm model with monolayer adsorption. The release profiles of KP released from KP-loaded CD-MNPs were rapid in initial 60 min and then gradually tend to level off, the release efficiency order was CM-β-CD-MNPs > β-CD-MNPs > DM-β-CD-MNPs, which was consistent with the order of inclusion capability. Therefore, the CD-MNPs were promising candidates for drug delivery.     

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

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.     

Optimal Development of a New Stable Nutraceutical Nanoemulsion Based on the Inclusion Complex of 2-Hydroxypropyl-β-cyclodextrin with Canthaxanthin Accumulated by Dietzia natronolimnaea HS-1 Using Ultrasound-Assisted Emulsification

Solubilizing the potent anticancer pigments in nanoemulsion (NE) systems containing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) is a novel and promising strategy to incorporate them into water-based drug formulations. The concentration effects of sunflower oil (SO, 5.61–17.39% w/w), surfactant mixture of Tween 80 (T80) and Span 20 (S20) (1:1 weight ratio, 3.95–14.05% w/w), and the inclusion complex of HP-β-CD with canthaxanthin (CTX) synthesized by Dietzia natronolimnaea HS-1 (2.61–14.39% w/w) were evaluated to formulate a stable NE using ultrasound-assisted emulsification. The NEs were evaluated regarding droplet size and polydispersity index (span), physical stability, turbidity, and loss of antioxidant activity (LAA). Response surface modeling showed that the NEs containing 12% T80/S20, 8.30% SO, and 12% CTX/HP-β-CD had the lowest droplet size (105.5 nm), span (0.394), droplet growth ratio (0.112), turbidity (0.139), and LAA (9.36%). The predicted values obtained were close to the experimental values, indicating the suitability of the constructed models. Transmission electron microscopy and confocal laser-scanning microscopy also demonstrated that the formed droplets of the NEs produced at optimal formulation were spherical in the range of 20–100 nm. A significant correlation was found between droplet size with stability (r = ?0.960, p < 0.01) and turbidity (r ² = 0.876, p < 0.01) values.