An investigation into the supramolecular structure,solubility, stability and antioxidant activity of rutin/cyclodextrin inclusion complex

The formation of supramolecular inclusion complexes between rutin and four cyclodextrins, namely β-cyclodextrin (β-CD), (2-hydroxypropyl)-α-cyclodextrin (HP-α-CD), (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD), and the effects of the complexation on the stability and antioxidant activity of rutin were investigated. Results from phase-solubility studies showed that rutin formed 1:1 stoichiometric inclusion complexes with HP-α-CD, β-CD, HP-β-CD and HP-γ-CD; the complexes formed with HP-γ-CD and HP-β-CD had the greatest stability constants, followed by β-CD and HP-α-CD. Thermodynamic studies demonstrate that the inclusion of rutin into HP-β-CD was an exothermic process which occurred spontaneously. Two-dimensional rotating-frame nuclear Overhauser effect spectroscopy (2D ROESY) ¹H NMR analyses show that the A ring of rutin was the part of the molecule that most likely inserted into the cavity of HP-β-CD, thus forming a supramolecular inclusion complex. Formation of such an inclusion complex conferred moderate degrees of protection to rutin from degradation by heat and UV radiation during storage, and significantly enhanced its antioxidant capacity as determined by three different procedures.     

Molecular microcapsules and inclusion interactions of eugenol with β-cyclodextrin and its derivatives

The molecular microcapsules and inclusion interactions of eugenol (EG) with β-cyclodextrin (β-CD) and three derivatives, heptakis-2,6-di-β-CD (DM-β-CD), mono [2-O-(2-hydroxyethyl)]-β-CD (HE-β-CD), and mono [2-O-(2-hydroxypropyl)]-β-CD (HP-β-CD) have been investigated by fluorescence and infrared spectroscopy. The interaction capacities of β-CDs with EG were as the following order: HP-β-CD > DM-β-CD > HE-β-CD > β-CD. Effects of pH value, concentrations of CDs, and temperature on the inclusion interactions were studied to obtain further knowledge on the mechanism of inclusion process. The formation constants were derived by the modified Hildebrand–Benesi equation. The results show that EG with CDs formed 1:1 host–guest complexes. The thermodynamic parameters of inclusion process, ΔG, ΔH and ΔS were determined. Based on the thermodynamic results, the inclusion process was deduced to be an exothermic and enthalphy-driven process. Furthermore, the IR spectra study has been made to confirm the inclusion and to provide information on the geometry of EG inside the cavity of β-CD.     

Evaluation of complex forming ability of hydroxypropyl-β-cyclodextrins

The complex forming ability of hydroxypropyl-β-cyclodextrins (HP-β-CDs) is highly influenced by the distribution of substituents and the average degree of substitution (DS), both the size of the cavity and the reactivity of CDs are altered when the hydroxyl groups are substituted. On the other hand, the guests themselves influence these interactions by their sizes and configurations. In the present study, 9 HP-β-CDs with different substitution patterns and DS, which have been investigated by the reductive-cleavage method and methylation analysis, were chosen. The interactions among HP-β-CDs and phenolphthalein (as a model for ‘larger spheriform’ guests) or p-methyl red (as a model for ‘smaller linear’ guests) were studied for determining the complex forming ability of HP-β-CDs. The results indicated that, compared with parent β-CD, HP-β-CDs have a lower ability to form inclusion complexes with the ‘larger spheriform’ guest molecules. With regard to the ‘smaller linear’ guest molecules, HP-β-CDs have a higher complex forming ability, especially the low DS value (<6.5) HP-β-CDs which have a ratio of DS (2 + 3) to DS (6) close to 1.     

环糊精对青蒿素的包合工艺研究

通过单因素及正交试验确定青蒿素与3种环糊精形成包合物的最佳条件,在此条件下利用相溶解度法测定青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数并计算包合反应前后的吉布斯自由能。结果表明：青蒿素与环糊精形成包合物的最佳条件为配比1:1(mol/mol)、包合温度40℃、包合时间5h、包合反应时溶液pH7,青蒿素与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数分别为80.06、58.68、116.96L/mol,反应前后的吉布斯自由能变化分别为－11.76、－10.93、－12.78kJ/mol。表明青蒿素与环糊精可以形成1:1型稳定的包合物,环糊精可以增大青蒿素的溶解度。     

青藤碱- 环糊精包合工艺的优化及包合常数测定

目的：考察青藤碱与环糊精形成包合物的最佳条件,测定青藤碱与不同环糊精的包合常数并进行体外释放研究。方法：通过单因素及正交试验确定青藤碱与不同环糊精形成包合物的最佳条件,并在此条件下利用相溶解度法测定青藤碱与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数,对包合物进行体外释放试验研究。结果：青藤碱与不同环糊精形成包合物的最佳条件为物质的量的1:1、包合温度50℃、包合反应3h、包合反应时溶液pH7,青藤碱与β-环糊精、羟丙基-β-环糊精、γ-环糊精的包合常数分别为501.1、150.0、600.3L/mol。结论：青藤碱与环糊精可以形成1:1型稳定的包合物,以环糊精为载体制备的不同青藤碱-环糊精包合物相对于青藤碱具有明显的缓释作用。     

Inclusion interactions and molecular microcapsule of <Emphasis Type="Italic">Salvia sclarea</Emphasis> L. essential oil with β-cyclodextrin derivatives

The inclusion interactions of β-cyclodextrin (β-CD), heptakis (2,6-di-methyl)-β-CD (DM-β-CD), mono[2-O-(2-hydroxyethyl)]-β-CD (2-HE-β-CD), and mono[2-O-(2-hydro-xypropyl)]-β-CD (2-HP-β-CD) with Salvia sclarea L. essential oil (SEO) were investigated by spectrofluorimetry, and the various factors affecting the inclusion process were examined in detail. At the same time, the formation constants at different temperatures and the thermodynamic parameters (ΔH, ΔS and ΔG) were calculated. The molecular microcapsule of SEO with β-CD was prepared by the method of saturated aqueous solution, and the stability of the microcapsule was determined. The results suggest that the stoichiometry of the SEO–CDs inclusion complexes was 1:1 (molar ratio), the formation constants of CDs with SEO decreased with the increasing of temperature, and the order that the capability associated with SEO was β-CD > DM-β-CD > 2-HE-β-CD > 2-HP-β-CD. The thermodynamic measurements showed that the inclusion process was an exothermic and enthalpy-driven process accompanied with a negative entropic contribution, and Van der Waals force plays an importance role in the process. In addition, the content of SEO in the microcapsule was 0.14 g/g and its stabilization was obviously improved.     

Characterisation of inclusion complex of trans-ferulic acid and hydroxypropyl-β-cyclodextrin

The inclusion complex of trans-ferulic acid (FA) with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared by the freeze-drying method and its characterisation was investigated by different analytical techniques including UV–visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy. All these approaches indicated that FA was able to form an inclusion complex with HP-β-CD, and the FA/HP-β-CD inclusion compounds exhibited different spectroscopic features and properties from FA. The stoichiometry of the complex was 1:1. The calculated apparent stability constant of the FA/HP-β-CD complex was 166.3 M⁻¹, and the water solubility of FA was significantly improved by phase solubility studies. Moreover, the irradiation-induced decomposition of FA in aqueous solution was markedly reduced by complexation with HP-β-CD. The results showed that HP-β-CD was a proper excipient for increasing solubility and stability of FA.     

茶多酚-β-环糊精包合物对羊肚冷藏期间肌原纤维蛋白氧化的影响

本实验将茶多酚(tea polyphenol,TP)与2-羟丙基-β-环糊精(2-hydroxypropyl-β-cyclodextrin,HP-β-CD)通过共沉积法制备出不同物质的量之比(n(HP-β-CD):n(TP)=1:0.5、1:1和1:2)的包合物,利用傅里叶变换红外光谱、热重分析和扫描电子显微镜对TP及...     

Preparation and stability of the inclusion complex of astaxanthin with hydroxypropyl-β-cyclodextrin

The inclusion complex of astaxanthin (ASX) with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared. Infrared spectroscopy (IR) proved the formation of the inclusion complex. The water solubility of the inclusion complex was >1.0 mg/ml, which is much better than that of ASX. The solid state thermal behaviour of the inclusion complex was investigated by thermogravimetric/differential thermal analysis (TG/DTA). The starting decomposition temperature of ASX was enhanced to about 290 °C. The stability of the inclusion complex in solution was also tested. Forming of the inclusion complex greatly enhanced the stability of ASX against light and oxygen. Furthermore, the release of ASX from the inclusion complex was controlled.     

Preparation and properties of phytosterols with hydroxypropyl β-cyclodextrin inclusion complexes

In order to enhance the solubility and bioavailability of phytosterols (PS), cyclodextrin–PS (CD–PS) inclusion complexes were prepared and the properties of PS-β-cyclodextrin (PS-β-CD) and the inclusion mechanism of its derivative hydroxypropyl β-cyclodextrin (PS-HP-β-CD) in solution were also evaluated. The effects of crucial parameters on cyclodextrin–sterol inclusion efficiency were optimized, including solvent type, β-CD/PS molar ratio, temperature, PS content and reaction time; 92–98?% inclusion efficiency was achieved under the conditions of HP-β-CD/PS ratio 3:1–4:1, PS concentration 15–20?mM, temperature 50–55?°C, reaction time 12?h. For β-CD host, butanol was a good solvent for PS inclusion reaction. The properties of CD–PS inclusion complexes were characterized by differential scanning calorimetric, scanning electron microscopy, UV–Vis scanning spectrophotometer (UV–Vis) and fourier transform infrared spectroscopy (FT-IR), which demonstrated that there are intermolecular hydrogen bonds between PS and HP-β-CD in inclusion complex, resulting in the formation of amorphous form. To clarify the mechanism of the increase in the solubility and bioactivity of HP-β-CD–PS inclusion complexes, the structure of CD as well as the interaction of the HP-β-CD–PS inclusion formation was elucidated. The conclusions indicated that PS-HP-β-CD showed higher water solubility with greater solubilizing and complexing capabilities than PS-β-CD and PS itself.     

Dual effect of β-cyclodextrin (β-CD) on the inhibition of apple polyphenol oxidase by 4-hexylresorcinol (HR) and methyl jasmonate (MJ)

Inhibition of red delicious apple polyphenol oxidase (PPO) by three non-related antibrowning agents has been studied at different substrate concentrations. The main apple polyphenol, cholorogenic acid (CA), has been used as a substrate. The three agents (β-cyclodextrin [β-CD], 4-hexylresorcinol [HR] and methyl jasmonate [MJ]) showed an inhibitory effect at every substrate concentration tested. From the inhibition constant (K_i) values, it was concluded that the inhibitors’ strength decreased in the order HR > β-CD > MJ. A combination of β-CD-HR had a synergic effect, which was not observed for the combination of β-CD-MJ. A competitive-type inhibition was obtained for HR with a K_i = 0.26 mM. β-CD and MJ behaved as mixed-type inhibitors, although more than one inhibitory mechanism is discussed for both agents.     

Complexation of resveratrol by native and modified cyclodextrins: Determination of complexation constant by enzymatic,solubility and fluorimetric assays

The complexation of resveratrol with native α-, β- and γ-cyclodextrins (CDs) and modified CDs (hydroxypropyl-β-(HP-β-CDs), maltosyl-β-(G₂-β-CDs), methyl-β-, carboxymethyl-β- and acetyl-β-cyclodextrins) was studied, and the complexation constants (K_c) were compared. The complexation constant between resveratrol and each type of CD was calculated using three different methods: enzymatic, solubility and fluorimetric. The K_c values obtained showed that HP-β-CDs with their very high K_c of 18,048 ± 625 M⁻¹, were the most effective for complexing resveratrol. Moreover, comparison of the results obtained by the three methods revealed that the fluorimetric method undervalued the K_c between resveratrol and all cyclodextrins, while the enzymatic and solubility methods were more precise for calculating the K_c between resveratrol and CDs, as demonstrated by the cyclodextrin-assay.     

Physicochemical characterisation of the supramolecular structure of luteolin/cyclodextrin inclusion complex

The formation of supramolecular inclusion complexes between luteolin and five cyclodextrins namely β-cyclodextrin (β-CD), methyl-β-cyclodextrin (M-β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) and glucosyl-β-cyclodextrin (G-β-CD) was investigated. Results from phase-solubility studies showed that luteolin formed 1:1 stoichiometric inclusion complexes with these cyclodextrins with the G-β-CD complex displaying the greatest stability constant. The supramolecular structure of the luteolin/G-β-CD complex was investigated by ultraviolet–visible spectroscopy (UV), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Results showed clearly the formation of a supramolecular complex in which the guest molecule, luteolin, was entrapped inside the cavity of the host, G-β-CD. The close association between luteolin and G-β-CD resulted in changes in some of the characteristic spectral, phase transitional and morphological properties of luteolin. Furthermore, molecular docking study showed that the complex was formed with the B ring of luteolin inserted into the cavity of G-β-CD.     

四种β-环糊精制备鞣花酸包合物的抗氧化性研究

利用鞣花酸（EA）与β-环糊精（β-CD）、羟丙基-β-环糊精（HP-β-CD）、二甲基-β-环糊精（DM-β-CD）、磺丁基-β-环糊精（SBE-β-CD）制备鞣花酸包合物,并使用高效液相色谱测定鞣花酸包合物的包合率,然后采用傅里叶红外光谱、X-射线衍射、扫描电镜对包合物进行表征,同时通过自由基清除能力评价鞣花酸包合物的抗氧化性。结果表明,EA/β-CD、EA/HP-β-CD、EA/DM-β-CD、EA/SBE-β-CD包合物的表观溶解度分别为0.037 3 mg/mL、0.123 2 mg/mL、0.093 8 mg/mL、0.095 6 mg/mL,包合率分别为82.58%、89.80%、87.42%、84.64%。鞣花酸与四种鞣花酸包合物清除DPPH自由基的半数清除率（EC50）值分别为6.47 μg/mL、6.31 μg/mL、3.45 μg/mL、3.63 μg/mL、3.92 μg/mL;清除ABTS自由基的EC50值分别为13.53 μg/mL、12.11 μg/mL、7.00 μg/mL、7.66 μg/mL、7.77 μg/mL;清除羟基自由基的EC50值分别为0.133 6 μg/mL、0.136 3 μg/mL、0.108 2 μg/mL、0.108 3 μg/mL、0.105 5 μg/mL;清除超氧阴离子自由基的EC50值分别为89.41 μg/mL、59.71 μg/mL、55.20 μg/mL、58.32 μg/mL、55.29 μg/mL。结果表明包合技术可以提高鞣花酸的溶解度与抗氧化能力。     

Encapsulation of cinnamon and thyme essential oils components (cinnamaldehyde and thymol) in β-cyclodextrin: Effect of interactions with water on complex stability

Thymol and cinnamaldehyde formed inclusion complexes with β-cyclodextrin (β-CD) upon mixing the components in aqueous media and subsequent freeze–drying, as confirmed by differential scanning calorimetry. The samples were stored at constant relative humidities (RH) from 22% to 97%, at 25 °C. The release of encapsulated compounds was determined following the melting enthalpy of each guest. Water sorption isotherms for β-CD and the complexes showed constant and low water sorption at RH < 80%, then the uptake of water increased abruptly. The amount of sorbed water at each RH was smaller for the complexes than for β-CD. The guest molecules displaced water molecules from inside the cavity of β-CD. No thymol or cinnamaldehyde release was detected at RH < 84%, and it increased abruptly from 84% RH, coincidentally with the abrupt increase of sorbed water. Water sorption significantly affects β-CD complexes stability, which is thus governed by the shape of the water sorption isotherm.     

羟丙基-β-环糊精对百里香挥发油包合作用的研究

采用正交实验与综合评分相结合的方法优化水溶液搅拌法制备百里香挥发油-羟丙基-β-环糊精（HP-β-CD）包合物的工艺条件,运用傅立叶变换红外光谱（FT-IR）对包合物进行表征,并利用气相色谱-质谱联用（GC-MS）技术对比分析了包合前后百里香挥发油的化学成分。结果表明,水溶液搅拌法制备百里香挥发油HP-β-CD包合物的最佳工艺条件为:百里香挥发油与HP-β-CD的体积质量比为1:10（mL:g）,包合温度30℃,搅拌时间2.5h,HP-β-CD的浓度5%,在此最佳工艺下,平均包合物得率与挥发油利用率分别为91.77%和81.94%,该工艺合理、稳定、可行,有效地提高了百里香挥发油的稳定性。FT-IR和GC-MS分析说明,百里香挥发油与HP-β-CD已经形成了包合物,包合前后百里香挥发油的主要化学成分基本相同,但挥发油中各组分的组成比例发生了一定程度的改变,包合对百里香挥发油的化学成分略有影响。      

Physical characteristics of fish oil encapsulated by β-cyclodextrin using an aggregation method or polycaprolactone using an emulsion–diffusion method

Fish oils have many dietary benefits, but have strong odours and are easily oxidised. For these reasons, β-cyclodextrin (β-CD) a water-soluble polymer and polycaprolactone (PCL) a water-insoluble polymer were used to encapsulate fish oil in this study. In addition, the stabilities of freeze-dried fish oil (FO) in encapsulated complexes were investigated to determine fish oil release rates at different relative humidities and storage temperatures. In order to facilitate the practical applications of the water-soluble and insoluble fish oil complexes produced, release studies of fish oil were performed in de-ionised water, NaCl solution and fish sauce. Based on our studies, fish oil loaded β-CD at a mixing ratio of 10:20 (β-CD:FO (w:w)) was the best composition in terms of encapsulation efficiency (84.1%), fish oil loading (62.7%), fish oil leakage after freeze-drying (11.0%), and eicopentaenoic acid (EPA) encapsulation efficiency (6.5%). In addition, fish oil release rates from β-CD particles were slower in de-ionised water and in 15% and 25% NaCl than in fish sauce at all mixing ratios between β-CD and FO. The storage stabilities of freeze-dried β-CD–FO complexes at 10:20 (w:w) mixing ratio at various relative humidities retained 97% of fish oil within the particles during 3 days. However, the release rate of fish oil from β-CD–FO complexes of 10:20 mixing ratio was accelerated in fish sauce. In terms of the emulsion–diffusion method, PCL more efficiently retarded the release of FO in liquid or powder form, although particles were broken by freeze-drying. It is supposed that PCL better protected FO because of its water insolubility.     

Physicochemical properties and mechanism of solubilised neohesperidin system based on inclusion complex of hydroxypropyl-β-cyclodextrin

A solvent method was used to prepare the inclusion compound of neohesperidin (NH) and hydroxypropyl-β-cyclodextrin (HP-β-CD) to improve the water solubility and thermal stability of NH. The physical and chemical properties and supramolecular structure of the inclusion complex were investigated by UV–vis spectroscopy, FTIR, SEM, TG-DTG, PXRD, NMR and molecular docking techniques. The results showed that the C-ring of NH was embedded in the cavity of HP-β-CD to form an inclusion complex. The phase has changed significantly, NH is completely dispersed in HP-β-CD in an amorphous state, and the two are combined in the form of non-covalent bonds such as hydrogen bonds or van der Waals forces. Through inclusion of HP-β-CD, the solubility of NH in water at 37 °C increased from 161.81 μg ml⁻¹ to 1927.12 μg ml⁻¹, and its stability was also significantly improved.     

Physicochemical and release characterisation of garlic oil-β-cyclodextrin inclusion complexes

Garlic oil (GO), rich in organosulphur compounds, has a variety of antimicrobial and antioxidant activities, however, its volatility and low physicochemical stability limit its application as food functional ingredients. The aim of this study was to investigate the physicochemical and release characterisation of inclusion complexes of GO in β-cyclodextrin (β-CD). The formation of GO/β-CD inclusion complex was demonstrated by different analytical techniques including Fourier transform-infrared spectroscopy, differential scanning calorimetry and X-ray diffractometry. The stoichiometry of the complex was 1:1. The calculated apparent stability constant of GO/β-CD complex was 1141 M⁻¹, and the water solubility of GO was significantly improved by the phase solubility study. Furthermore, the release of GO from the inclusion complex was determined at a temperature range from 25 to 50 °C and in an acidic dissolution medium (pH 1.5), respectively. The release rate of GO from the inclusion complex was controlled.     

Heat stability of allyl isothiocyanate and phenyl isothiocyanate complexed with randomly methylated β-cyclodextrin

Inclusion complexation reactions between isothiocyanates (ITCs), namely, allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC), and randomly methylated β-cyclodextrin (RM-β-CD) displayed “A_P” type solubility isotherms, indicating continuous increases in the stoichiometry of the inclusion complexes. The complex powders were prepared by spray drying and their heat stability was studied by thermal analysis and heat treatment in paraffin. The solid-state dissociation reactions were satisfactorily described by the unimolecular decay law. The apparent activation energy of dissociation, E_D, was determined to be 48 and 58 kJ/mol, respectively, for the AITC/RM-β-CD and PITC/RM-β-CD complexes, while the apparent activation energies of decrease of ITCs in paraffin, E_P for the pure AITC and PITC, and the corresponding inclusion complexes were 26, 48, 44, and 54 kJ/mol, respectively, suggesting volatility suppression and physical stabilisation by inclusion complexation as the plausible mode of stabilisation of the ITCs in paraffin. A compensation effect in the kinetics of depletion of the ITCs in paraffin was established.