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Encompassment of Benzyl Isothiocyanate in cyclodextrin using ultrasonication methodology to enhance its stability for biological applications

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... BITC with proven cytotoxic effects requires a suitable carrier system that can deliver it slowly at tumor sites. Reports are scarce (12)(13)(14) that have investigated the plausible improvement of the biopharmaceutical potential of BITC. It, therefore, calls for the adoption of more effectual and novel delivery strategies for enhancing the bioavailability and bio-accessibility of BITC. ...
... CDs can simultaneously serve the function of a carrier; improve the organoleptic properties by curbing acute odor and solubility enhancer, making them an impeccable choice for nutraceutical formulations. The controlled release of BITC from the CDs can effectively suppress the proliferation rate of cancer cells by extending the retention time of BITC (12). Thus, the aptness of CDs as the delivery wagon for BITC was first examined using physicochemical characterization followed by biochemical and cellular functions in well-established tumor mimicking models. ...
... The inclusion complex of BITC with β-CD (β-CD BITC) and with HP-β-CD (HP-β-CD BITC) was prepared by using a probe sonication technique. The method has been reported in our previous work (12). Briefly, 0.044 mol of BITC was added dropwise to an equimolar solution of β-CD (or HP-β-CD) with a minimal solvent mixture (ethanol:water::2:8). ...
Preprint
Benzyl isothiocyanate (BITC), an organic dietary compound, is allied with a major role in the potential chemopreventive effects. BITC has acknowledged rising attention as a therapeutic compound to be used in medicine because of its high potency and characteristic biopharmaceutical properties, like high permeability with marginal aqueous solubility. The highly volatile and hydrophobic nature brought a need to provide a suitable delivery-matrix to BITC to exploit its pharmacological potential to the fullest. It has been successfully incorporated in β-CD and HP-β-CD using acoustic forces and thoroughly characterized using UV-vis spectroscopy, FTIR, DSC, TEM, and SAXS. The complexation helped in masking the acute odour, achieving a controlled release of BITC, and made its use viable by prolonging the retention time and thereby sustaining the biological effects. Different models like Higuchi, first-order kinetic decay, Korsmeyer-Peppas model were applied, suggesting a diffusion-controlled mechanism of release. Also, the bioaccessibility and stability of BITC in an in vitro digestion model was evaluated. The main objective of the present work was to systemically study the credibility of BITC-CD complexes in well-established tumor mimicking 2D cell culture models and produce a conclusive report on its chemotherapeutic activity. The in vitro anti-cancer activity of BITC and the formed sonochemical complexes was confirmed by MTT assay and further evaluated using apoptosis assay and production of ROS like moieties. Cell cycle analysis was done to evaluate the growth inhibitory mechanism of BITC. Strikingly, BITC and its complexes showcased ROS generation and lysosome-mediated cell death. Effect on cell migration was assessed using wound healing assay. The results promptly suggest the functional efficacy of the CDs in releasing BITC and attest the ability of the complexes to provide alternate to otherwise remedially sparse triple-negative breast cancer.
... β-CD:SLT, HPβ-CD:SLT, and SBEβ-CD:SLT showed 79.12 ± 1.13%, 74.26 ± 0.24%, and 99.12 ± 2.35% antibacterial activity against S. aureus and 89.27 ± 1.45%, 2.91 ± 1.94%, and 99.31 ± 2.31% antibacterial activity against E. coli, respectively (Fig. 7). These findings were in good agreement with those of previous studies [22,32,51]. Overall, these results showed that the SBEβ-CD:SLT inclusion complex had a greater inhibitory effect against S. aureus and E. coli than the β-CD:SLT and HPβ-CD:SLT complexes. ...
... The cell membrane and cytoplasmic organelles of bacteria are the main sites of drug action. β-CDs may have improved the ability of SLT to access these regions by increasing its water solubility [22,32,51]. Thus, a significant percentage of the antibacterial activity ingested by the active SLT drug in β-CDs inclusion complexes SLT was preserved without any modification, indicating their exceptional suitability as antimicrobial candidates that offer a potential exciting for the future. ...
... SLT uptake into the MCF-7 cells upon 24 h of incubation with high concentrations of β-CDs:SLT (up to 100 μg/mL) was observed using confocal microscopy (Fig. 8B). These results demonstrated that β-CDs:SLT can permeate the cell membrane and enter cells [51,55,56]. The improved cellular activity observed for the complex concerning SLT alone was probably due to the balance between two factors: (i) the solubilizing effect of β-CDs on SLT and (ii) the binding constant value of the inclusion complex. ...
Article
The inclusion complexes of the salsalate drug (SLT) with β-cyclodextrin derivatives (β-CDs); namely, β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HPβ-CD), and sulfobutylether-β-cyclodextrin (SBEβ-CD) are synthesized using the ultrasound process. The enhanced aqueous solubility of SLT is demonstrated by phase solubility diagram and optical spectroscopy, showing the inclusion complexation of β-CDs and SLT with a 1:1 stoichiometry. The β-CDs:SLT inclusion complexes exhibit potent bacterial activity against Staphylococcus aureus and Escherichia coli and reduce the cytotoxic effects of SLT on MCF-7 cells. The β-CDs:SLT complexes display further important activity for the inhibition of α-amylase and α-glucosidase, indicating their antidiabetic capability. The designed and synthesized inclusion complexes of SLT with β-CDs are widely expected to have potential applications in the preparation of novel pharmaceutical formulations containing SLT.
... The solid EOC/MβCD-ICs were synthesized by following the US synthetic method [14]. In brief, 0.04 M of MβCD was dissolved in 20 mL of distilled water:ethanol solvent mixture (4:1) and 0.04 M of EOC (CA or ISOE) was added. ...
... In the present study, two solid ICs of selected EOC and MβCD were produced via the eco-friend US synthetic method as shown in Fig. 1 under optimal experimental conditions [14]. These US assisted EOC/ MβCD-ICs were initially investigated by TGA in order to verify the true IC formation between the volatile guests and MβCD in solid state. ...
... Additionally, the appearance of two new diffraction peaks with weak intensity at 2θ~31.27°, 35.68°(in CA/MβCD-IC) and 28.08°, 40.46°(in for the IC of benzyl isothiocyanate with HPβCD in the US synthetic process [14]. Accordingly, the PXRD substantiates the results that were obtained from TGA, DSC, 1 H NMR and FT-IR characterization techniques for the EOC/MβCD-ICs that were prepared by the US synthetic process. ...
Article
Essential oils derived from medicinal plants are prosperous sources of active components having high biological potential. Cuminaldehye and isoeugenol, are hydrophobic essential oil components (EOC), are showing drastic limitations in their applications by low water solubility and the respective volatility. Methyl-β-cyclodextrin inclusion complexes (MβCD-ICs) were prepared in aqueous solution and in solid state with the EOC via the ultrasonication method, an energy saving, high efficiency and eco-friend technique, aim to extend their aqueous solubility and biological properties. UV-Vis absorption, fluorescence, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), proton nuclear magnetic resonance (1H NMR) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and computational simulations confirmed the formation of EOC/MβCD-ICs. Result of solubility studies proved the enhanced solubilization of EOC in the presence of MβCD in aqueous and double reciprocal profiles substantiated the guest/host stoichiometry of 1:1. TGA and DSC studies indicated the improved stability of EOC in MβCD-ICs. The efficiency of ICs in terms of the antioxidant activity was verified and the IC displayed higher antioxidant activity compared to that of free EOC, as determined by free radical scavenging assay. Finally, the antibacterial effect of EOC/MβCD-ICs against gram-positive Staphylococcus aureus and gram-negative Escherichia coli bacteria was demonstrated. Overall results not only revealed the potential of MβCD on the bioavailability, solubility and stability, but also that the intensification caused by the IC may be greater that the antioxidant and antibacterial effects of the selected EOC for this study.
... The US is broadly utilized as a dispersing tool in physical, chemical and material science. Consequently, the US has been widely applied to many food industries, such as food preservation, food processing and extraction process [11][12][13]. ...
... Recently, the US technique has been broadly employed to fabricate the ICs of native as well as modified-CDs. For instance, Mehta et al. prepared and studied the ICs of benzyl isothiocyanate with βCD and HPβCD using ultrasonic at 180 W for 300 sec to overcome the hindrance of low solubility and high volatility for the biological applications [12]. ...
Article
Ultrasound is an energy saving, simple, high efficiency and eco-friend physical technology. In this study, the inclusion complex of cuminaldehyde (CUM), a major constituent of cumin essential oil, with 2-hydroxypropyl-β-cyclodextrin (HPβCD) was synthesised with the aid of ultrasound. The solid CUM/HPβCD-IC was characterized using Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. The stability constants were evaluated by phase solubility, absorption and fluorimetry methods, and were found to be 168, 122 and 256 M ⁻¹ , respectively. FT-IR and molecular modeling studies indicated that the phenyl ring with the aldehyde group of CUM was inserted into the hydrophobic HPβCD cavity. Further, the efficacy of CUM/HPβCD-IC for inactivation of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was investigated through plate colony counting method. According to the results, the inactivation was 100 ± 0.06% for both E. coli and S. aureus bacteria. The results demonstrated the inclusion of CUM within the harmless HPβCD cavity assisted by ultrasound technology, contributing the improvements of water solubility, thermal stability and antibacterial activities.
... Fig. 8). As expected from their chemical structure and physical characteristics, natural and modified CDs (methylated and sulfated) have similar thermal behavior [56,57]. Mass loss and water content are clearly different quantities [56]. ...
Article
A potentially active water-soluble anti-viral with lesser toxic material from the Oseltamivir (OTV) has been produced by the sonication method. The formed material has been further characterized by UV-visible, FT-IR, powder XRD, SEM, TGA/DTA, ROESY, XPS, AFM and etc., The results of DFT analysis have proven that inclusion complexes (ICs) are theoretically and energetically more advantageous models and structures have also been proposed based on the results. Analysis of drug release has been carried out at three pH levels, and it is revealed the analysis is most helpful at acidic pH levels for the ICs with S-CD over H-CD. Over OTV without CDs, OTV:S-CD-ICs exhibited a very less cytotoxic ability on cancer cell lines than ICs with M-CD. ICs enhanced the viral inactivation nature of OTV. This study provides for the first time a full characterization of ICs of OTV with CDs and highlights the impact of complex formation on pharmacological activity.
... It has been reported that a significant synergic effect was evidenced when norfloxacin was combined with the ethyl and propyl esterified derivatives, suggesting that lipophilicity plays an important role in the antibacterial activity [39]. However, BITC is a highly volatile substance limiting its wide application [40]. Uppal et al. showed that the antibacterial activities of BITC chitosan nanoparticles (preparations) were greater than those of BITC by performing an inhibition zone assay and determining the MIC [15]. ...
Article
Full-text available
The aim of this study was to develop inclusions formed by γ-cyclodextrin (γ-CD) and three isothiocyanates (ITCs), including benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC), and 3-methylthiopropyl isothiocyanate (MTPITC) to improve their controlled release for the inhibition of Staphylococcus aureus (S. aureus). These inclusion complexes were characterized using X-ray diffraction, Fourier-transform infrared, thermogravimetry, and scanning electron microscopy (SEM), providing appropriate evidence to confirm the formation of inclusion complexes. Preliminary evaluation of the antimicrobial activity of the different inclusion complexes, carried out in vitro by agar diffusion, showed that such activity lasted 5–7 days longer in γ-CD-BITC, in comparison with γ-CD-PEITC and γ-CD-MTPITC. The biofilm formation was less in S. aureus treated with γ-CD-BITC than that of BITC by using crystal violet quantification assay and SEM. The expression of virulence genes, including sarA, agr, cp5D, cp8F, clf, nuc, and spa, showed sustained downregulation in S. aureus treated with γ-CD-BITC for 24 h by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the growth of S. aureus in cooked chicken breast treated with γ-CD-BITC and BITC was predicted by the Gompertz model. The lag time of γ-CD-BITC was 1.3–2.4 times longer than that of BITC, and correlation coefficient (R2) of the secondary models was 0.94–0.99, respectively. These results suggest that BITC has a more durable antibacterial effect against S. aureus after encapsulation by γ-CD.
... This system would be suitable for stabilization and controlled release of benzyl isothiocyanate. Uppal et al. (2017) used ultrasound to assist benzyl isothiocyanate microencapsulation through inclusion complex, and reported a physicochemical characterization of the system. The inclusion complex kept antibacterial activity, and then the authors speculate that they also should keep the pharmacological properties. ...
Article
Full-text available
The health–promoting properties of sulforaphane (SFN) are well known, however its instability is still a hurdle for its incorporation into food matrices. SFN can be stabilized by microencapsulation, technique sparingly explored for isothiocyanates so far. This review summarizes the advances in microencapsulation of SFN and other isothiocyanates. Encapsulation efficiency and degradation rate of sulforaphane in different systems are compared and discussed. Ionic gelation and complex coacervation seem more adequate for SFN, both underexplored until now. Drying conditions after chemical encapsulation are determinant, most likely related to thermal degradation of SFN. The current information is insufficient to identify the most adequate encapsulation system and the optimal process conditions to stabilize SFN aiming at its incorporation into food matrices. Accordingly, encapsulation conditions should be investigated, which arises as a new research line. Stability studies are encouraged since this information will help in designing SFN microencapsulation strategies that extend the industrial application of this promising health-promoting compound.
... No significant difference in the color and transparency was seen from the composite film (Figure 3b), which preliminarily indicates that the incorporation of BITC−α−CD would not bring about alterations to the appearance of the CS film matrix. To better illustrate the physiochemical properties of the pure CS and CS−BITC−α−CD composite films, the color measurements, particle size measurements, surficial roughness, XRD analysis is a common and desirable method to measure and characterize the crystal structures of the test samples [42]. Since BITC under ambient temperature is at aqueous status, the XRD information of which is difficult to acquire [38]. ...
Article
Full-text available
A bioactive packaging material based on chitosan (CS) incorporated with benzyl isothiocyanate (BITC) and α−cyclodextrin (α−CD) was fabricated to evaluate its preservative effects on fresh beef stored at 4 °C for 12 d according to the quality analysis. The Fourier-transform infrared (FTIR) spectrum revealed that the major structural moiety of BITC was embedded in the cavity of α−CD, except for the thiocyanate group. FTIR and X-ray diffraction analysis further verified that intermolecular interactions were formed between the BITC−α−CD and CS film matrix. The addition of BITC−α−CD decreased the UV light transmittance of pure CS film to lower than 63% but still had enough transparency for observing packaged items. The CS−based composite film displayed a sustainable antibacterial capacity and an enhanced antioxidant activity. Moreover, the total viable counts, total volatile base nitrogen, pH, thiobarbituric acid–reactive substances, and sensory evaluation of the raw beef treated with the CS−based composite film were 6.31 log colony-forming unit (CFU)/g, 19.60 mg/100 g, 6.84, 0.26 mg/kg, and 6.5 at 12 days, respectively, indicating the favorable protective efficacy on beef. These results suggested that the fabricated CS−based composite film has the application potential to be developed as a bioactive food packaging material, especially for beef preservation.
... Watercress (Nasturtium officinale) is an enriched source of gluconasturtiin, the GSL precursor of PEITC [31]. It has been previously documented that PEITC is a powerful antioxidant [242][243][244][245][246][247][248][249][250][251], cancer chemo-preventive [252][253][254][255][256][257][258][259][260] and antimicrobial [261][262][263][264][265] agent. Several studies have demonstrated that the formation of PEITC is easily affected by various factors like temperature and pH. ...
Article
Full-text available
Isothiocyanates are biologically active secondary metabolites liberated via enzymatic hydrolysis of their sulfur enriched precursors, glucosinolates, upon tissue plant disruption. The importance of this class of compounds lies in their capacity to induce anti-cancer, anti-microbial, anti-inflammatory, neuroprotective, and other bioactive properties. As such, their isolation from natural sources is of utmost importance. In this review article, an extensive examination of the various parameters (hydrolysis, extraction, and quantification) affecting the isolation of isothiocyanates from naturally-derived sources is presented. Overall, the effective isolation/extraction and quantification of isothiocyanate is strongly associated with their chemical and physicochemical properties, such as polarity-solubility as well as thermal and acidic stability. Furthermore, the successful activation of myrosinase appears to be a major factor affecting the conversion of glucosinolates into active isothiocyanates.
... XRD is a major tool to study the crystal form of a substance. Previous studies have demonstrated that the peak shape and intensity changes of XRD are significant evidence for complex formation [36]. X-ray diffraction analysis of MeβCD and CsNIs is presented in Fig. 2B. ...
Article
This study aimed to overcome the current challenges of active oil encapsulation, such as the complex preparation process, low encapsulation efficiency, and poor water solubility. Using mechanochemical method prepared celery seed oil/methyl-β-cyclodextrin nanocapsule (CsNIs). The entrapment efficiency was determined by UV–vis spectrophotometry, and characterized by DLS, FT-IR, XRD, SEM and TEM. A mouse model of hyperuricemia induced by potassium oxate (PO) was used to investigate the antihyperuricemia and nephroprotective effects of the CsNIs. CsNIs formed by hydrogen bonding of Celery Seed Oil (CsO) with MeβCD had high encapsulation efficiency (98.39%), and had more stable antioxidant activity under sunlight exposure. The water solubility was improved by 30-fold. CsNIs will self-assemble into nano-spheres in aqueous solution and be slowly released to 77.2% in 48 h. Uric acid levels and the degree of renal injury were significantly lower in hyperuricemia (HUA) mice. In this study, the water solubility and stability of celery seed oil were improved. And it provides a green, simple, and efficient encapsulation strategy for the encapsulation of active oils.
... Examples of successful applications of the use of cyclodextrins include encapsulation substrates such as drugs, food products, and natural pesticides [2][3][4][5][6][7]. The synthesis of β-cyclodextrin inclusion complexes can be accomplished through methods such as co-precipitation [8,9], kneading [10,11], ultrasonication [12,13], freeze-drying [14], spray-drying [15], and the use of supercritical fluids [16]. Synthetic methods currently available are simple, require no (or limited amount of) organic solvents and no additional purification or cleanup steps, and use non-toxic materials, which makes the preparation of β-cyclodextrin inclusion complexes a desired and environmentally friendly process that falls into the green-synthesis approach [17,18]. ...
Article
Full-text available
Cyclodextrin inclusion complexes have been successfully used to encapsulate essential oils, improving their physicochemical properties and pharmacological effects. Besides being well-known for its effects on cats and other felines, catnip (Nepeta cataria) essential oil demonstrates repellency against blood-feeding pests such as mosquitoes. This study evaluates the tick repellency of catnip oil alone and encapsulated in β-cyclodextrin, prepared using the co-precipitation method at a 1:1 molar ratio. The physicochemical properties of this inclusion complex were characterized using GC-FID for encapsulation efficiency and yield and SPME/GC-MS for volatile emission. Qualitative assessment of complex formation was done by UV-Vis, FT-IR, 1H NMR, and SEM analyses. Catnip oil at 5% (v/v) demonstrated significant tick repellency over time, being comparable to DEET as used in commercial products. The prepared [catnip: β-CD] inclusion complex exerted significant tick repellency at lower concentration of the essential oil (equivalent of 1% v/v). The inclusion complex showed that the release of the active ingredient was consistent after 6 h, which could improve the effective repellent duration. These results demonstrated the effective tick repellent activity of catnip essential oil and the successful synthesis of the inclusion complex, suggesting that β-CDs are promising carriers to improve catnip oil properties and to expand its use in repellent formulations for tick management.
Article
In this study, the inclusion complex (IC) of thymol with 2-hydroxypropyl-β-cyclodextrin (HPβCD) was fast synthetized by ultrasonic technology and its antifungal activities were evaluated. The thymol/HPβCD-IC was characterized by UV-vis absorption spectroscopy, fluorescence emission spectroscopy, powder X-ray diffraction, FT-IR, ¹H-NMR, TGA and DSC. The phase solubility studies proved that the aqueous solubility of thymol was significantly improved by forming the inclusion complex with HPβCD, and the thermal stability analysis showed that thymol/HPβCD-IC had a better thermal stability than pure thymol. The in vitro antifungal activities of thymol/HPβCD-IC against Botrytis cinerea, Penicillium digitatum and Alternaria alternata were significantly improved compared with pure thymol. Furthermore, the gray mold rot of tomatoes was evidently inhibited by thymol/HPβCD-IC treatment in vivo study. Therefore, the complexation with HPβCD assisted by ultrasound is a promising approach to solubilize and stabilize thymol for application as an antifungal agent in fruit preservation.
Article
The use of ultrasonic waves for the preparation of inclusion complexes in pharmaceutical industries has increased, owing to their versatility, promising nondestructive capability, and short reaction time. 5-Hydroxytryptophan (5-HTP), a precursor of serotonin, is used therapeutically, in the clinical setting, for psychiatric disorders such as anxiety and depression. In this study, 5-HTP is used as a guest molecule to prepare β-cyclodextrins (CDs; β-CD, HPβ-CD, and SBEβ-CD) inclusion complexes with the assistance of the ultrasonic method. The solubility of 5-HTP increases linearly as the concentration of CDs increased, confirming the 1:1 stoichiometry of the complex, obtained using UV-visible and fluorescence spectroscopy. The structural characteristics of the solid inclusion complexes are analyzed using various spectroscopic and microscopic techniques such as FTIR spectroscopy, PXRD, TGA, and FE-SEM. Molecular modeling elucidates the most stable inclusion model and phase solubility studies indicate that 5-HTP and SBEβ-CD form a 1:1 inclusion complex with an apparent stability constant of 1592.5 M−1. Furthermore, in vitro cytotoxicity studies show that the CDs:5-HTP complex has a better antitumor efficacy than pure 5-HTP. Thus, ultrasonication can be utilized as an advanced, time-saving, and cost-effective method for the generation of CD:5-HTP inclusion complexes, resulting in the potential development of anticancer drugs.
Article
An innovative sonication method has been developed to produce inclusion complexes (ICs) of Oseltamivir (OTV) which is a potentially water-soluble anti-viral agent with lesser cytotoxicity. Proton signals and chemical shifts of OTV without any ambiguity confirm the formation of ICs with β-Cyclodextrin (B-CD) and Hydroxypropyl-β-cyclodextrin (H-CD). ICs are also supported by their atomic percentages as secondary evidence using XPS analysis. Analysis of drug release at three pH levels revealed the slow release of the OTV from ICs and also suitable for viral inactivation. A very less cytotoxic ability on cancer cell lines and enhanced the viral inactivation of OTV after being made into water-soluble ICs.
Article
E. coli O157:H7 is one of the most common food-borne pathogens and usually related to contaminated vegetables. This study was to prepare an effective antibacterial agent and applied in vegetable juices. In this study, β-cyclodextrin inclusion complexof CUM (CUM /βCD-IC) was prepared using ultrasonication technique and then treated with cold nitrogen plasma (CNP) to observe its effect in the physicochemical and antibacterial properties of CUM/βCD-IC. Various characterization techniques such as fluorescence, fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) confirmed the formation of IC between CUM and βCD. Phase solubility and double reciprocal profiles studies proved the enhanced solubility of CUM with increasing amount of βCD and the guest/host stoichiometry of 1:1. Computational modeling and FT-IR indicated that the phenyl ring with isopropyl chain of CUM is inserted in the hydrophobic βCD. Investigations of thermal properties proved that the βCD-IC formation improved the stability of CUM. Antibacterial test results indicated that CNP-CUM/βCD-IC exhibited better antibacterial activity than CUM/βCD-IC. After CNP-CUM/βCD-IC treatment, it was observed by TEM that the cell membrane of E. coli O157:H7 was broken. In addition, the antibacterial activity of CNP-CUM/βCD-IC in vegetable juices was carried out and the findings revealed that CNP-CUM/βCD-IC has an excellent antibacterial effect on vegetable juices.
Article
The ultrasound method was used to prepare tea tree oil/hydroxypropyl-β-cyclodextrin inclusion complexes (TTO/HP-β-CD IC). The optimal ultrasonic conditions were 120 W at 40 °C for 70 min, and the optimal ratio of core to wall was 1 : 10, resulting in an encapsulation efficiency of 80.63 %. Physicochemical characterization of the IC demonstrated successful complexation of TTO/HP-β-CD and the enhanced thermal stability of TTO. Characterization was done using scanning electron microscopy, UV–Vis absorption spectroscopy, fourier transform infrared spectroscopy, nuclear magnetic resonance, thermogravimetry/derivative thermogravimetry and differential scanning calorimetry. The rate of sustained-release of TTO and its anti-Monilinia fructicola activity after prolonged storage were tested in vitro. TTO showed sustained released from TTO/HP-β-CD IC over the course of a month, both at 4 °C and 20 °C. TTO/HP-β-CD IC stored for 12 months inhibited the growth of M. fructicola, in vitro, as efficiently as freshly prepared IC. TTO/HP-β-CD IC has greater stability and long-lasting antifungal properties than unencapsulated TTO. TTO/HP-β-CD IC could inhibit the growth of M. fructicola in vitro test and in peach fruit.
Article
Phthalyl sulfacetamide (PSA) is an antibiotic sulfonamide. In this study, inclusion complexes (ICs) of α- (αCD) and β-cyclodextrin (βCD) were prepared in aqueous solution and in solid state with PSA using the ultrasonication (US) process. The structural and thermal characteristics of the US-assisted ICs were investigated by UV–Vis absorption, fluorescence, Fourier transform infrared (FT-IR) spectroscopy, proton nuclear magnetic resonance (¹H NMR) spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and computational modeling techniques. The improved dissolution of PSA in the presence of CD was confirmed by UV–Vis absorption. The experimental and computational modeling studies proved that the stoichiometry of the ICs was 1:1 for PSA/CD-ICs. It was also observed that the IC formation between βCD and PSA was the strongest when compared to αCD host. The enhanced thermal stability of PSA was achieved for PSA/CD-ICs when compared to pure form of PSA. FT-IR, ¹H NMR and computational modeling studies indicated that biologically active sulfonamide group (ring-A) of PSA was encapsulated in the hydrophobic CD cavity. The stability of ICs in terms of energetic, thermodynamic and electronic properties was verified and the PSA/βCD-IC revealed higher stability compared to that of PSA/αCD-IC, as determined by PM3 method.
Chapter
The development of nanoscience and nanotechnology has revolutionized every sphere of human life - Food, water, shelter, and clothing. To meet the changing food demands, increase the shelf life and durability of the fragile food items, encapsulation is carried out. The chapter aims to throw light on the need for nanoencapsulation in the food industry, the merits, and demerits of employing nanotechnology in the food industry. Various nanoencapsulation techniques have been discussed with special focus on coacervation and inclusion complexation methodologies. These are the two simplest techniques which make the encapsulation process facile and quick. Coacervation process is a colloidal phenomenon which is sub-divided into simple and complex coacervation. Inclusion complexation works on the concept of host-guest chemistry, using the lock and key mechanism. An attempt has been made to give a deep insight into these processes, describing their types, advantages and the factors influencing them. A brief overview of literature has also been done to give a glimpse of the use of these two techniques in the current research arena.
Article
Benzyl Isothiocyanate (BITC), a nutraceutical belonging to the mustard family exhibits excellent antitumor and antimicrobial properties. Despite its prodigious potential, the lacuna in the practical application is due to hydrophobicity, high volatility, receded bioavailability, and acute odor. Owing to the entrenched advantages of the nanostructured colloidal systems, a new rhamnolipid based nanoemulsion was synthesized employing the heating-stirring-sonication method using GRAS ingredients to overcome the shortcomings of BITC. The nanoemulsion has been optimized to exhibit good long-term stability in a salt solution (50–200 mM) and at different pH conditions. The physicochemical properties were assessed using DLS, TEM, UV-Vis and FTIR spectroscopy. Hemolysis and biocompatibility studies validated the bio-safety of the engineered nano-wagon. The system demonstrated high entrapment efficiency along with a sustained release. MTT assay performed indicated increased cytotoxicity of BITC NEm against MDA MB 231 breast cancer cells as compared to BITC alone. Qualitative and quantitative cell uptake studies performed using confocal spectroscopy and flow cytometry, respectively, validated that BITC was completely encapsulated in the nanocarrier and the formulation acted as an efficient and compatible carrier. Furthermore, the antibacterial assay of BITC loaded nanoemulsion showed promising results against strains of E. coli and S. aureus proving it to be a safe alternative for overcoming the pressure of resistant strains.
Article
The formation of host-guest complex between benzyl isothiocyanate (BITC) and β-cyclodextrin (β-CD) was studied using dispersion-corrected density functional theory calculations. The complexation process was monitored using molecular docking simulations, natural bond orbital (NBO) technique, nuclear magnetic resonance (¹H NMR) chemical shift calculations and non-covalent interactions (NCI) analysis. All these approaches are consistent with experimental findings. The calculated complexation energy was negative indicating the formation of inclusion complex. The most stable complexation of BITC involves the inclusion of its aromatic moiety in β-CD cavity (model A) in accord with experimental NMR chemical shift data. The non-covalent interactions (NCI) based on the reduced density gradient (RDG) analysis reveal that mainly weak Van der Waals intermolecular interactions between BITC and β-CD provide and ensure stability for the complexation process.
Article
The arena of drug delivery is intensifying; hence, it becomes seemingly significant to develop efficient fabrication methodologies while, contemporaneously preserving human health and environment for future generations. The present work dwells upon designing of Ceria nanoparticles (Nps) based drug delivery system in a reproducible and rather restrained controlled manner using nano-emulsion as the template and further, exploiting them as potential candidates in treating one of the pernicious diseases, Cancer. The cavitation procedure employed reinforces the rate of synthesis, resulting in a swift fabrication. The as-synthesized Nps (size ≤ 5 nm) were loaded with Benzyl isothiocyanate (BITC) and in-depth characterization procedures were conducted exploiting Fourier transform infrared spectroscopy, X-ray diffraction, Raman spectroscopy, Zeta potential and Zeta sizer. Small angle X-ray scattering and Brunauer–Emmett–Teller reveal the morphological disposition of these synthesized systems. The structural investigation was carried out using field emission electron microscopy. The biocompatibility studies having Bovine serum albumin (BSA) as a model biomolecule signified the configuration of ground state complex between the ceria loaded BITC (CB) Nps and BSA. Further, the thermodynamic parameters for the complex formation were assessed using fluorescence, UV–visible and circular dichroism spectroscopy. The hemolysis was conducted to evaluate the safety levels of the carrier system on the blood components. The MTT assay demonstrated the adeptness of the formulation on MDA MB-231 cell lines. The proficiency of CB Nps against the bacterial infections is strikingly indicated by the antimicrobial studies which proves that the nano formulation is monumental in inhibiting the growth of E. coli and S. aureus.
Article
Isoeugenol is a natural dual antioxidant/prooxidant. In this research, the inclusion complex (IC) of isoeugenol with 2-hydroxypropyl-β-cyclodextrin (HPβCD) was prepared via the ultrasound (US) method. The US assisted isoeugenol/HPβCD-IC was investigated by various characterization techniques such as UV–Vis absorption, fluorescence, powder X-ray diffraction, Fourier transform infrared spectroscopy, thermal gravimetric analysis and differential scanning calorimetry. Absorption, fluorescence and infrared studies indicated that the alkyl chain of isoeugenol was deeply included in the HPβCD cavity. Through determinations of phase solubility and water solubility studies, significant enhancement of isoeugenol water solubility was confirmed after IC formation with the HPβCD. Thermal data proved that the IC formation significantly enhanced the thermal stability of isoeugenol. Antioxidant test results indicated that isoeugenol/HPβCD-IC exhibited better antioxidant activity than free isoeugenol due to its solubility enhancement. Furthermore, the isoeugenol/HPβCD-IC showed higher antibacterial activity of 96 ± 0.2% and 97 ± 0.5% against Staphylococcus aureus and Escherichia coli bacteria, respectively.
Article
In this work, the solution blow spinning (SBS) technique was used to rapidly fabricate the thymol (THY)/2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes loaded chitosan (CS)/polycaprolactone (PCL) nanofibrous films for fruit preservation and packaging. XRD results indicated that the THY/HPβCD inclusion complexes were successfully incorporated into the CS/PCL nanofibers. The nanofibrous films had an increase of average diameters of nanofibers from 243.84 nm to 560.55 nm, an enhancement of water vapor permeability, a decrease of the crystallinity, and a hydrophilic surface after the incorporation. FTIR and thermal analysis showed that the thermal stability was also improved due to the formation of hydrogen bonds between THY/HPβCD inclusion complexes and CS/PCL nanofibers. The developed films obtained a long-term continuous release of THY during 240 h, and had a good antifungal activity in vitro and in vivo. The above results indicated the promising prospects of SBS in developing antifungal nanofibrous films for postharvest fruit.
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Production of Shiga toxins by enterohemorrhagic Escherichia coli (EHEC) which is responsible for the pathogenicity of these strains, is strictly correlated with induction of lambdoid bacteriophages present in the host's genome, replication of phage DNA and expression of stx genes. Antibiotic treatment of EHEC infection may lead to induction of prophage into a lytic development, thus increasing the risk of severe complications. This, together with the spread of multi-drug resistance, increases the need for novel antimicrobial agents. We report here that isothiocyanates (ITC), plant secondary metabolites, such as sulforaphane (SFN), allyl isothiocyanate (AITC), benzyl isothiocynanate (BITC), phenyl isothiocyanate (PITC) and isopropyl isothiocyanate (IPRITC), inhibit bacterial growth and lytic development of stx-harboring prophages. The mechanism underlying the antimicrobial effect of ITCs involves the induction of global bacterial stress regulatory system, the stringent response. Its alarmone, guanosine penta/tetraphosphate ((p)ppGpp) affects major cellular processes, including nucleic acids synthesis, which leads to the efficient inhibition of both, prophage induction and toxin synthesis, abolishing in this way EHEC virulence for human and simian cells. Thus, ITCs could be considered as potential therapeutic agents in EHEC infections.
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In this study, solid geraniol/cyclodextrin inclusion complexes (geraniol/CD-IC) were successfully prepared by using three types of native CD (alpha-CD, beta-CD and gamma-CD). The modeling studies for inclusion complexation between CD and geraniol were performed by using ab initio techniques. Both experimentally and theoretically, the cornplexation efficiency between geraniol and gamma-CD was higher; therefore, geraniol/gamma-CD-IC was chosen and then incorporated into polyvinyl alcohol (PVA) nanofibers (NF) via electrospinning. The scanning electron microscopy imaging elucidated that the aggregates of geraniol/gamma-CD-IC crystals were distributed in the PVA NF, whereas bead-free and uniform PVA and PVA/geraniol NF without CD-IC were obtained. Higher thermal stability of geraniol was observed in the electrospun PVA/geraniol/gamma-CD-IC NF, However, geraniol molecules having volatile nature could not be preserved without CD-IC during electrospinning or during storage; therefore, the complete evaporation of geraniol in PVA/geraniol NF was unavoidable even after one day of its production. On the contrary, the loss of geraniol was minimal (similar to 10%) for PVA/geraniol/gamma-CD-IC NF even after storage of these NF for two years owing to inclusion complexation. Our study demonstrated that electrospun NF incorporating CD-IC may be quite applicable in food industry, e.g.: active food packaging or functional foods, due to very high surface area and nanoporous structure of NF; high thermal stability and enhanced durability of active agents and functional food ingredients.
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Campylobacter jejuni is a widespread pathogen responsible for most of the food-borne gastrointestinal diseases in Europe. The use of natural antimicrobial molecules is a promising alternative to antibiotic treatments for pathogen control in the food industry. Isothiocyanates are natural antimicrobial compounds, which also display anticancer activity. Several studies described the chemoprotective effect of isothiocyanates on eukaryotic cells, but the antimicrobial mechanism is still poorly understood. We investigated the early cellular response of C. jejuni to benzyl isothiocyanate by both transcriptomic and physiological approaches. The transcriptomic response of C. jejuni to benzyl isothiocyanate showed upregulation of heat shock response genes and an impact on energy metabolism. Oxygen consumption was progressively impaired by benzyl isothiocyanate treatment, as revealed by high-resolution respirometry, while the ATP content increased soon after benzyl isothiocyanate exposition, which suggests a shift in the energy metabolism balance. Finally, benzyl isothiocyanate induced intracellular protein aggregation. These results indicate that benzyl isothiocyanate affects C. jejuni by targeting proteins, resulting in the disruption of major metabolic processes and eventually leading to cell death.
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In this work, we illustrate the usefulness of cyclodextrins, namely, methyl-β-cyclodextrin (MβCD), an amorphous, methylated derivative of the natural β-cyclodextrin (βCD), as a tool to form an inclusion complex with omeprazole (OME), a poorly water soluble drug. Solid binary systems between OME and MβCD were prepared experimentally in a stoichiometry 1:1 by different techniques (physical mixing, kneading, spray-drying and freeze-drying). Afterward these products were characterized by Fourier transformation-infrared spectroscopy (FTIR); X-ray diffractometry (XRD) and scanning electron microscopy (SEM). The results obtained suggest that spray-drying and freeze-drying methods yield a higher degree of amorphous entities suggesting the formation of inclusion complexes between OME and MβCD.
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Plants produce a number of antimicrobial substances and the roots of the shrub Salvadora persica have been demonstrated to possess antimicrobial activity. Sticks from the roots of S. persica, Miswak sticks, have been used for centuries as a traditional method of cleaning teeth. Diverging reports on the chemical nature and antimicrobial repertoire of the chewing sticks from S. persica led us to explore its antibacterial properties against a panel of pathogenic or commensal bacteria and to identify the antibacterial component/s by methodical chemical characterization. S. persica root essential oil was prepared by steam distillation and solid-phase microextraction was used to sample volatiles released from fresh root. The active compound was identified by gas chromatography-mass spectrometry and antibacterial assays. The antibacterial compound was isolated using medium-pressure liquid chromatography. Transmission electron microscopy was used to visualize the effect on bacterial cells. The main antibacterial component of both S. persica root extracts and volatiles was benzyl isothiocyanate. Root extracts as well as commercial synthetic benzyl isothiocyanate exhibited rapid and strong bactericidal effect against oral pathogens involved in periodontal disease as well as against other Gram-negative bacteria, while Gram-positive bacteria mainly displayed growth inhibition or remained unaffected. The short exposure needed to obtain bactericidal effect implies that the chewing sticks and the essential oil may have a specific role in treatment of periodontal disease in reducing Gram-negative periodontal pathogens. Our results indicate the need for further investigation into the mechanism of the specific killing of Gram-negative bacteria by S. persica root stick extracts and its active component benzyl isothiocyanate.
Article
An important issue in food technology is that antimicrobial compounds can be used for various applications, such as the development of antimicrobial active packaging materials. Yet most antimicrobial compounds are volatile and require protection. In the present study, the inclusion complexes of 2-nonanone (2-NN) with β-cyclodextrin (β-CD), were prepared by a co-precipitation method. Entrapment efficiency (EE), thermal analysis (DSC and TGA), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR), sorption isotherms and antifungal activity were evaluated for the characterization of the inclusion complex (β-CD:2-NN). A higher EE was obtained (34.8%) for the inclusion complex 1:0.5 than for other molar rates. Both DSC and TGA of the inclusion complexes showed the presence of endothermic peaks between 80 °C and 150 °C, attributed to a complexation phenomenon. Antimicrobial tests for mycelial growth reduction under atmospheric conditions proved the fungistatic behaviour of the inclusion complexes against Botrytis cinerea.
Article
A distinctive, effortless, proficient and innovative process for preparation of an inclusion complex (IC) of resveratrol (Res) with hp-β-CD was developed. The methodology overcame the hindrance of low solubility of Res which is a potential anticancer agent and makes its use more practical. The strategy involved the utilization of a microwave meant for conventional use and the process of sonication in the laboratory. It considerably saved time and labour besides cutting down on energy consumption. The prepared inclusion complexes were characterised by FTIR, UV-visible absorption spectroscopy, NMR, TGA, DSC, XRD and CHNS analysis. Phase solubility studies along with Gaussian studies proved the formation of a 1:1 complex whose physical nature and stability were studied using XRD and UV-visible absorption spectroscopy, respectively. This effortless and economical process could pave the way for the formation of inclusion complexes of other nutraceuticals and pharmaceuticals. This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2015.
Article
Abstract Supramolecular interaction between 2,2′-Bipyridine (BPY) and β-Cyclodextrin (β-CD) has been investigated in solution and solid state. Non-covalent interaction between BPY and β-CD was studied in solution using absorption and fluorescence spectroscopy. Inclusion complex of BPY and β-CD was prepared in solid state by co-precipitation method and it was characterized using Fourier Transform Infra-red spectroscopy (FT-IR), Thermal analysis, Scanning Electron Microscopy (SEM), Powder X-ray diffractometry (XRD) and Atomic Force Microscopy (AFM). Binding constant values and 1:1 stoichiometry of the inclusion complex were calculated using Benesi-Hildebrand plots at 303 K. Using continuous variation method the 1:1 stoichiometry has been confirmed for BPY: β-CD complex. Thermodynamic parameter, ΔG of inclusion complex formation was determined and the negative value indicated that the inclusion process was an exergonic and spontaneous process. The most probable model of BPY: β-CD inclusion complex suggested by molecular docking studies was in good agreement with the results obtained by experimental methods.
Article
The inclusion complex of benzyl isothiocyanate (BITC), extracted from papaya seed with β-cyclodextrin (β-CD), was prepared. Different analytical techniques, such as Fourier transform infrared spectroscopy, thermal analysis, X-ray diffractometry, particle size distribution analysis and (1)H Nuclear magnetic resonance analysis, were used to investigate the characterization of the inclusion complex (BITC-β-CD). All these approaches indicated that the inclusion complex was capable of being formed. The inclusion complex exhibited different spectroscopic and thermodynamic features and properties from BITC, and we deduced the possible inclusion modes for BITC-β-CD. The calculated apparent stability constant of the BITC-β-CD was 600.8l/mol, and the aqueous solubility of BITC was indistinctively improved by phase solubility studies. The results illustrated that β-CD was a proper excipient for increasing the stability and controlled release of BITC. Thus, β-CD complexation technology would be a promising approach, in expanding the application of BITC as a food antibacterial agent. Copyright © 2015 Elsevier Ltd. All rights reserved.
Article
The cyclodextrins (CDs) complexation technique was performed for the enhancement of hydroxylation yield from dehydroepiandrosterone (DHEA) by Colletotrichum lini ST-1. Using DHEA/methyl-β-cyclodextrine (M-β-CD) or DHEA/hydroxypropyl-β-cyclodextrine (HP-β-CD) inclusion complexes as substrate (10 g/L), the hydroxylation yields were increased by 14.98% and 20.54% respectively, and the biotransformation course was shortened by 12 h. X-ray diffractometry, differential scanning calorimetry, and phase solubility analyses showed an inclusion complex was formed between CDs and DHEA at a molar ratio of 1:1, which remarkably increased the solubility of DHEA, and then improved substrate biotransformation efficiency and hydroxylation yield. Meanwhile, results of thermodynamic parameters (ΔG, ΔH, ΔS and Ks) analysis revealed the complexation process was spontaneous and DHEA/CDs inclusion complex was stable. Scanning electron microscopy and transmission electron microscopy showed that the enhancement of DHEA hydroxylation yield also depended on the improvement of cell permeability through interaction between cytomembrane and CDs. These results suggested that the CDs compexation technique was a promising method to enhance steroids hydroxylation yield by increasing steroids solubility and decreasing membrane resistance of substrate and product during biotransformation process.
Article
The aim of this work is to increase the stability and water solubility of resveratrol by complexation with different cyclodextrins. Furthermore, physical–chemical properties of each inclusion compound were investigated. Complexes of resveratrol with cyclodextrins both native (α, β, γ) and modified (2-hydroxypropyl-β-cyclodextrin, dimethyl-β-cyclodextrin) were obtained by using the suspension method. An inclusion complex with β-cyclodextrin was also prepared by using the microwave. Solid state characterization of the products was carried out using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (DRX); solution studies were performed by UV–Vis spectrophotometry and 1H-NMR spectroscopy. Phase solubility profiles with all cyclodextrins employed were classified as AN type, indicating the formation of 1:1 stoichiometric inclusion complexes. Stability constants (K c) from the phase solubility diagrams were calculated. Stability studies in the solid state and in solution were performed; the photodegradation by UV–Vis spectrophotometry was monitored. The isomerization rate trans to cis, in ethanol solution, decreased with inclusion. The dissolution studies revealed that resveratrol dissolution rate was improved by the formation of inclusion complexes.
Article
Kinetic equations of the form ln[frsol″>;g(α)/Tc″] =ln[AE/φR] + c′ -c″ ln E - c″() are proposed for the evaluation of activation parameters from non-isothermal experiments. The values of c′, c″ and c″ have been derived using the already established linear dependence of (i) the logarithm of the Arrhenius temperature integral ln p(x) on x (=), (ii) its slope on x−1 and (iii) its intercept on In x, respectively. The ln p(x) values were computed from the recently proposed series and the closed-form three-term approximations. The kinetic parameters computed with the proposed equations show better agreement for theoretical TG curves than do the well known methods. The equations have equal practical significance in the kinetic analysis of non-isothermal processes.
Article
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 1141M−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.
Article
A new approximate formula for temperature integral is proposed. The linear dependence of the new fomula on x has been established. Combining this linear dependence and integration-by-parts, new equation for the evaluation of kinetic parameters has been obtained from the above dependence. The validity of this equation has been tested with data from numerical calculating. And its deviation from the values calculated by Simpson's numerical integrating was discussed. Compared with several published approximate formulae, this new one is much superior to all other approximations and is the most suitable solution for the evaluation of kinetic parameters from TG experiments.
Article
The thermal behaviour of benzoic and salicylic acids is compared with the behaviour of 1:1 molar ratio physical and kneaded mixtures of these acids with each of three different cyclodextrins (b-, hydroxypropyl-b-, and g-cyclodextrin). Differential scanning calorimetry and thermogravimetry coupled with evolved gas analysis by Fourier transform infrared spectroscopy were used for the thermal studies and X-ray powder diffraction and infrared spectroscopy provided complementary information. Thermal studies of benzoic acid with the cyclodextrins showed significant interactions in both physical and kneaded mixtures of benzoic acid/b-cyclodextrin and benzoic acid/hydroxypropyl-b-cyclodextrin. Interactions in the kneaded benzoic acid/g-cyclodextrin mixtures were the most extensive as might be expected for the cyclodextrin with the largest molecular cavity. The results for the salicylic acid/b-cyclodextrin and salicylic acid/hydroxypropyl-b-cyclodextrin mixtures were similar to those for benzoic acid/b-cyclodextrin and benzoic acid/hydroxypropyl-b-cyclodextrin. Again, the kneaded salicylic acid/g-cyclodextrin mixture showed the most interaction.
Article
The inclusion complexes of α-, β-cyclodextrin (α-, β-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 α-CD form 1:1 inclusion complexes with KD values of 1.33×10−5molL−1, 4.85×10−6molL−1 and 7.47×10−5molL−1, respectively. The obtained KD values of the inclusion complexes of above-mentioned three sulphonated azo dyes ligands binding to β-CD in turn are 3.93×10−6molL−1, 6.50×10−6molL−1 and 1.12×10−4molL−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 α-CD and Orange II inclusion complexes are 4.05×10−4molL−1 and 4.60×10−7 (molL−1)2, respectively. 3.94×10−5molL−1 and 1.72×10−7(molL−1)2 are the KD,1 and KD,2 of β-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.
Article
a b s t r a c t An approach mainly based on thermogravimetric analysis (TGA) was developed to evaluate the stoichiometric ratio (SR, guest to host) of the guest–-cyclodextrin (Guest--CD) inclusion complexes (4-cresol--CD, benzyl alcohol--CD, ferrocene--CD and decanoic acid--CD). The present data obtained from Fourier transform-infrared (FT-IR) spectroscopy showed that all the -CD-based inclusion com-plexes were successfully prepared in a solid-state form. The stoichiometric ratios of -CD to the relative guests (4-cresol, benzyl alcohol, ferrocene and decanoic acid) determined by the developed method were 1:1, 1:2, 2:1 and 1:2, respectively. These SR data were well demonstrated by the previously reported X-ray diffraction (XRD) method and the NMR confirmatory experiments, except the SR of decanoic acid with a larger size and longer chain was not consistent. It is, therefore, suggested that the TGA-based method is applicable to follow the stoichiometric ratio of the polycrystalline -CD-based inclusion complexes with smaller and shorter chain guests.
Article
THE use of thermogravimetric data to evaluate kinetic parameters of solid-state reactions involving weight loss (or gain) has been investigated by a number of workers1–4. Freeman and Carroll2 have stated some of the advantages of this method over conventional isothermal studies. To these reasons may be added the advantage of using one single sample for investigation. However, the importance of procedural details, such as crucible geometry, heating rate, pre-history of sample, and particle size, on the parameters has yet to be fully investigated. It is also necessary to ensure accurate temperature measurement, both for precision and also to detect any departure from a linear heating rate due to endo- or exo-thermic reactions. (The effect of these may be largely eliminated by the use of small samples.) In our present work (using a Stanton HT–D thermobalance) the sample temperature is measured directly by means of a thermocouple the bead of which is positioned in or near the sample, depending on crucible design, the wires of which run down a twin-bore rise rod. The connexion between the end of the thermocouple wires on the balance arm and the terminal block is made by 0.001 in. platinum and platinum/rhodium wires5. It has been shown that these wires do not affect the performance of the balance but act merely as a subsidiary damping. From the terminal block compensated cable leads to the cold junction and a potentiometric arrangement for direct measurement of the thermocouple output.
Article
Benzyl isothiocyanate (BITC) and phenylethyl isothiocyanate (PEITC) are two poorly water-soluble plant components that can form inclusion complexes with β-cyclodextrin (β-CD), namely, β-cyclodextrin−BITC and β-cyclodextrin−PEITC, that are two water-soluble complexes. The inclusion complexes were prepared by two independent processes: physical mixing and coprecipitation. The content of guest molecules in the complexes was measured by UV spectrophotometry. Response surface design (RSD) was applied to optimize the preparation conditions of said complexes. The results showed that the embedding ratios for β-CD−BITC and β-CD−PEITC were 94.9% and 94.1%, respectively. Variance analysis revealed that the mass ratio and the inclusion temperature were two important factors in terms of inclusion action. The optimum conditions for the inclusion of β-CD−BITC were a mass ratio of 0.17 and an inclusion temperature of 57.99 °C, and those for β-CD−PEITC were a mass ratio of 0.0057 and an inclusion temperature of 64.87 °C. The inclusion complexes prepared were qualified by thermal methods [thermogravimetry (TG) and differential scanning calorimetry (DSC)], Fourier transform infrared (FTIR) spectroscopy, and X-ray powder diffraction (XRD). The thermal analysis of β-CD and the two complexes indicated that an interaction between the guest and host molecules did occur. BITC and PEITC could be partially embedded in the hydrophobic cavity of β-CD, so the formation of the said complexes was established. The X-ray and FTIR results support this indication of inclusion behavior.
Article
A new mathematical interpretation of thermogravimetric traces enables one to determine conveniently the kinetic parameters of pyrolysis reactions. The slope of a straight line plot of a function of the weight fraction left vs. the temperature gives the activation energy of pyrolysis. The good agreement between values of activation energy obtained by the new equations and reported literature values for some polymers and hydrated salts serves to validate the new approach. The, usefulness of these equations is further demonstrated by their application to two other polymeric systems.
Article
The study of the complexation of trans-resveratrol with natural cyclodextrins (CDs) in aqueous medium under different physico-chemical conditions of pH or temperature is essential if this antioxidant compound is to be used successfully in the food industry as ingredient of functional foods, due its poor stability, bioavailability and solubility. In this paper, a rapid, simple and sensitive determination of the apparent formation constant of trans-resveratrol/CD complexes by HPLC in aqueous medium has been investigated for first time. It can be observed that trans-resveratrol forms a 1:1 complex with α-, β- and γ-CD. The highest value of the apparent formation constant (KF=1922±89M(-1)) was found for β-CD and a strong dependence of KF on pH can be seen in the region where the trans-resveratrol begins the deprotonation of their hydroxyl groups. Moreover, an increase in the system's temperature produced a decrease in the values of KF. Finally, to gain information on the mechanism of the trans-resveratrol affinity for CD, the thermodynamic parameters of the complexation were obtained. Copyright © 2008 Elsevier Ltd. All rights reserved.
Article
Solid inclusion compounds of Berberine chloride (Berb) and β-cyclodextrin (β-CD) were prepared by grinding method and co-evaporation method. The formation and thermal characterization of solid inclusion compounds were investigated by Fourier transform-infrared (FT-IR) and differential scanning calorimetry (DSC). The results showed that the inclusion compounds of Berb and β-CD could be prepared by the grinding method and co-evaporation method. DSC analysis afforded the quantitative evaluations of inclusion efficiency and showed that grinding method offered higher inclusion efficiency compared with co-evaporation method. Influence of grinding time on inclusion ratio of Berb with β-CD was further studied by DSC measurement. DSC analysis could be considered as a rapid qualitative and quantitative analytical method in the preparation of cyclodextrins inclusion compounds.
Article
Isothiocyanates (ITCs), the breakdown products of glucosinolates found primarily in species of Brassicaceae (Cruciferae), are potential anti-cancer compounds. This review compiles data on how through different modes of action ITCs and their synthetic counterparts target leukemia.
Article
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 K(1:1) 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.
Article
A thermodynamic study of the inclusion process between 2-chlorobenzophenone (2ClBP) and cyclomaltoheptaose (β-cyclodextrin, β-CD) was performed using UV-vis spectroscopy, reversed-phase liquid chromatography (RP-HPLC), and molecular modeling (PM6). Spectrophotometric measurements in aqueous solutions were performed at different temperatures. The stoichiometry of the complex is 1:1 and its apparent formation constant (K(c)) is 3846M(-1) at 30°C. Temperature dependence of K(c) values revealed that both enthalpy (ΔH°=-10.58kJ/mol) and entropy changes (ΔS°=33.76J/Kmol) are favorable for the inclusion process in an aqueous medium. Encapsulation was also investigated using RP-HPLC (C18 column) with different mobile-phase compositions, to which β-CD was added. The apparent formation constants in MeOH-H(2)O (K(F)) were dependent of the proportion of the mobile phase employed (50:50, 55:45, 60:40 and 65:35, v/v). The K(F) values were 419M(-1) (50% MeOH) and 166M(-1) (65% MeOH) at 30°C. The thermodynamic parameters of the complex in an aqueous MeOH medium indicated that this process is largely driven by enthalpy change (ΔH°=-27.25kJ/mol and ΔS°=-45.12J/Kmol). The results of the study carried out with the PM6 semiempirical method showed that the energetically most favorable structure for the formation of the complex is the 'head up' orientation.
Article
Cyclodextrins (CDs) are able to enhance the solubility, stability and bioavailability of several bioactive hydrophobic compounds by complex formation. They can also be used for removal of undesired components (such as cholesterol, off-flavors or bitter components) present in foods. Although many patents account for the use of cyclodextrins for removal of cholesterol from dairy foods, there is no available information on the effect of water on encapsulation efficiency and on the stability of sterols in CDs. The aim of this work was to study the inclusion properties and the factors affecting the encapsulation and stability of cholesterol in β-cyclodextrin (BCD). The optimum encapsulation conditions (ligand-CD molar ratio, stirring time and temperature), and stability of the complexes as a function of storage time and water content were analyzed. Phase solubility study pointed out the formation of 1:1 stoichiometric complexes between cholesterol and β-cyclodextrin, which was influenced by temperature variations. The process was shown to be exothermic and energetically favored. The presence of cholesterol greatly modified the BCD water sorption curves, being the amount of adsorbed water smaller in the combined systems. The principal 'driving force' for complex formation is the substitution of the high-enthalpy water molecules by an appropriate hydrophobic ligand. The freeze-dried complexes probed to be stable at different storage conditions. The phase solubility and stability data obtained could be essential for selecting the most suitable conditions when CDs are employed either for removing cholesterol or to incorporate functional ingredients (i.e. sitosterol) in the development of innovative food products.
Article
Peripheral blood is the primary source of lymphoid cells for investigation of the human immune system. Its use is facilitated by Ficoll-Hypaque density gradient centrifugation-a simple and rapid method of purifying peripheral blood mononuclear cells (PBMC) that takes advantage of the density differences between mononuclear cells and other elements found in the blood sample. Thus, cells are distributed in the solution in layers based on the differences in their density/size. Additional purification methods can be employed as the mononuclear cell sample can be purified from monocytes by adherence or by exposure to L-leucine methyl ester; these methods are described for both procedures. Cord blood and peripheral blood from infants contain immature cells, including nucleated red cells, which can result in significant contamination of the mononuclear cell layer, and removal of these cells requires additional steps that are described. The isolation procedures presented here can also be applied to cell populations derived from tissues.
Article
1. The corresponding cysteine conjugate was formed when the GSH (reduced glutathione) or cysteinylglycine conjugates of benzyl isothiocyanate were incubated with rat liver or kidney homogenates. When the cysteine conjugate of benzyl isothiocyanate was similarly incubated in the presence of acetyl-CoA, the corresponding N-acetylcysteine conjugate (mercapturic acid) was formed. 2. The non-enzymic reaction of GSH with benzyl isothiocyanate was rapid and was catalysed by rat liver cytosol. 3. The mercapturic acid was excreted in the urine of rats dosed with benzyl isothiocyanate or its GSH, cysteinyl-glycine or cysteine conjugate, and was isolated as the dicyclohexylamine salt. 4. An oral dose of the cysteine conjugate of [14C]benzyl isothiocyanate was rapidly absorbed and excreted by rats and dogs. After 3 days, rats had excreted a mean of 92.4 and 5.6% of the dose in the urine and faeces respectively, and dogs had excreted a mean of 86.3 and 13.2% respectively. 5. After an oral dose of the cystein conjugate of [C]benzyl isothiocyanate, the major 14C-labelled metabolite in rat urine was the corresponding mercapturic acid (62% of the dose), whereas in dog urine it was hippuric acid (40% of the dose). 5. Mercapturic acid biosynthesis may be an important route of metabolism of certain isothiocyanates in some mammalian species.
Article
1. Both after ingestion of benzyl isothiocyanate (BITC), a compound with antibacterial properties, and after consumption of garden cress known to contain BITC, the metabolite N-acetyl-S-(N-benzylthiocarbamoyl)-L-cysteine was identified in the urine of volunteers by comparative chromatography. 2. The chemical structure of the metabolite was confirmed by elemental analysis and by comparison of the i.r. and 1H-n.m.r. spectra with those of the synthetic product. 3. On average 53.7% of the dose of BITC was excreted as this metabolite by the renal route. 4. The metabolite was excreted rapidly, appearing with maximum concentrations some 2-6 h after dosing and being essentially complete 10-12 h after administration.
Article
Substantial quantities of isothiocyanates are released upon consumption of normal amounts of a number of cruciferous vegetables. Some of these naturally occurring isothiocyanates such as phenethyl isothiocyanate (PEITC), benzyl isothiocyanate (BITC) and sulforaphane are effective inhibitors of cancer induction in rodents treated with carcinogens. A large amount of data demonstrate that isothiocyanates act as cancer chemopreventive agents by favorably modifying carcinogen metabolism via inhibition of Phase 1 enzymes and/or induction of Phase 2 enzymes. These effects are quite specific, depending on the structure of the isothiocyanate and carcinogen. One of the most thoroughly studied examples of isothiocyanate inhibition of rodent carcinogenesis is inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis by PEITC. This occurs because PEITC blocks the metabolic activation of NNK, resulting in increased urinary excretion of detoxified metabolites. Similar effects on NNK metabolism have been observed in smokers who consumed watercress, a source of PEITC. On the basis of these observations and knowledge of the carcinogenic constituents of cigarette smoke, a strategy for chemoprevention of lung cancer can be developed.
Article
Inclusion complexation between celecoxib, a specific cyclooxygenase II inhibitor, and beta-cyclodextrin (beta-CD) was studied in solution and solid state. Drug cyclodextrin complexes were prepared by spray drying while physical mixtures were obtained by simple blending. Inclusion complexes were characterized by nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), and polarimetry. Phase solubility analysis was carried out to determine the stability constant. Solubility studies revealed the existence of a 1:1 complex between celecoxib and beta-CD. NMR studies suggested a strong interaction between celecoxib and beta-CD prepared by spray drying. XRD and SEM analysis illustrated that celecoxib existed as an amorphous complexed form in spray-dried complexes. Dissolution studies showed that the celecoxib entrapped in spray-dried complexes dissolved much faster than the uncomplexed drug and physical mixtures. The data obtained suggest that celecoxib forms an inclusion complex with beta-CD in solution and solid state, which was confirmed by various analytical techniques. A shorter t50% of dissolution is found for the formulation prepared by spray drying when compared on a weight basis in a USP II apparatus.
Article
In grapevine (Vitis vinifera L.), defense responses after microbial infection or treatment with elicitors involve accumulation of phytoalexins, oxidative burst, and the synthesis of pathogenesis-related proteins. Oligosaccharide fractions from fungal or algal cell walls efficiently induce the defense responses, but a detailed analysis of the elicitor-plant cell surface interaction at the molecular level is precluded by the lack of chemically pure oligosaccharide elicitors. A grapevine liquid cell culture system was used to examine the properties of cyclodextrins (CDs) as inducers of defense responses. This work shows that the chemically pure heptakis(2,6-di-O-methyl)-betaCD caused a dramatic extracellular accumulation of the phytoalexin resveratrol and changes in peroxidase activity and isoenzymatic pattern. Other modified CDs tested on several grapevine cell lines resulted in different eliciting capacities of CDs and different sensibilities of the cell lines. The spent medium of elicited cultures was shown to disturb Botrytis cinerea growth in a plate assay.
Phase-solubility techniques
  • T Higuchi
  • A Connors
T. Higuchi, A. Connors, Phase-solubility techniques, Adv. Anal. Chem. Instrum. 4 (1965) 117-122.
  • H N Yuan
  • S J Yao
  • L Q Shen
  • J W Mao
H.N. Yuan, S.J. Yao, L.Q. Shen, J.W. Mao, Phase-solubility techniques, Ind. Eng. Chem. Res. 48 (2009) 5070-5078.