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Energy efficient, facile and cost effective methodology for formation of inclusion complex of resveratrol with hp-β-CD
Abstract
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.
... As shown in Fig. 1B, the characteristic peaks of Res were observed at 1606, 1587, 1384, and 965 cm − 1 , which corresponded to the C-C aromatic double bond stretching, C-C olefinic, C-O stretching and trans olefinic bond, respectively. The feature peak at 3407 cm − 1 was assigned to the vibration of the hydrogen bonded OH groups of HP-β-CD, and some other intense peaks at 1654, 1156, and 1032 cm − 1 were respectively ascribed to the H-O-H bending, C-O and C-O-C stretching [35]. In the spectra of the two solid physical mixtures (HP-β-CD+Res), all characteristic bands of Res and HP-β-CD were clearly observed, suggesting weaker or no interaction between Res and HP-β-CD in a solid physical mixture. ...
... The XRD pattern of HP-β-CD displayed a broad peak, implying an amorphous structure. Clearly, the HP-β-CD+Res solid physical mixture exhibited corresponding characteristic peaks of Res and HP-β-CD, while the diffraction peaks of Res were invisible in the HP-β-CD@Res, further confirming the formation of inclusion complex [35]. The interaction of host-guest complexes was also characterized by 1 H NMR spectroscopy. ...
... As shown in Fig. 1E and F, the chemical shift (δ) of Res wrapped by HP-β-CD moved to the higher field due to the host-guest interaction of HP-β-CD and Res. And the protons inside the HP-β-CD cavity showed the maximum chemical shift change,△δ, which was consistent with the previous report [35]. ...
Hydrogel patch-based stem cell transplantation and microenvironment-regulating drug delivery strategy is promising for the treatment of myocardial infarction (MI). However, the low retention of cells and drugs limits their therapeutic efficacies. Here, we propose a prefixed sponge carpet strategy, that is, aldehyde-dextran sponge (ODS) loading anti-oxidative/autophagy-regulating molecular capsules of 2-hydroxy-β[email protected] (HP-β[email protected]) is first bonded to the rat's heart via capillary removal of interfacial water from the tissue surface, and the subsequent Schiff base reaction between the aldehyde groups on ODS and amino groups on myocardium tissue. Then, an aqueous biocompatible hydrazided hyaluronic acid (HHA) solution encapsulating mesenchymal stem cells (MSCs) is impregnated into the anchored carpet to form [email protected]@HP-β[email protected] hydrogel in situ via click reaction, thus prolonging the in vivo retention time of therapeutic drug and cells. Importantly, the HHA added to outer surface consumes the remaining aldehydes to contribute to nonsticky top surface, avoiding adhesion to other tissues. The embedded HP-β[email protected] molecular capsules with antioxidant and autophagy regulation bioactivities can considerably improve cardiac microenvironment, reduce cardiomyocyte apoptosis, and enhance the survival of transplanted MSCs, thereby promoting cardiac repair by facilitating angiogenesis and reducing cardiac fibrosis.
... But concerted efforts are being made to find an effortless and proficient method which would make the process more cost-effective. A number of complexation studies are available in the literature (Kaur et al. 2015), most common among them is the simple physical stirring using the magnetic stirrer. Although this standard procedure is easy, it needs long hours for the complexation process to complete. ...
... The commercial microwaves are expensive and involve high maintenance cost inflating the overall price of the market product. Lately, the cavitation technique is being explored in this area which is showing promising results (Kaur et al. 2015). It neither requires laborious, endless stirring nor is the use of any toxic solvents required. ...
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.
... Further, the addition of hydroxypropyl group to -CD remarkably enhances its various properties like stability, aqueous solubility and oral bioavailability. It in fact reduces the toxicity compared to -CD [6,7]. The toxicity of cyclodextrin depends on the route and dose of administration. ...
Curcumin was modified with 2-hydroxypropyl-β-cyclodextrin (HPβCD) to enhance its bioavailability. The modified curcumin was loaded into gelatin-carrageenan microparticles to control the drug release behavior. The different analytical techniques like Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy (RS), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) indicated the formation of the samples. The solubility of the modified curcumin was checked visibly and by using UV-VIS spectroscopy & optical microscopy as well. The effect of surfactant on process yield, drug loading & encapsulation efficiency, swelling and drug release from the microparticles was checked. The samples exhibited more swelling and hence drug release was more in basic compared to acidic medium and the percentage increased with increase in time. The modified curcumin, on examining in both breast and lung cancer cell lines, manifested better anticancer activity compared to curcumin as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, clonogenic assay and apoptosis assay. However, the microparticles didn’t reveal better anticancer activities compared to curcumin and modified curcumin. Further, all the prepared samples were found to be non-toxic to human peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs).
... Previous studies have used various kinds of nanocarriers to encapsulate resveratrol, including hydrophobic proteins (Iris et al., 2015), cyclodextrin metal-organic framework/chitosan (CD-MOF/CS) nanocapsules (Qiu et al., 2020). Liposomes (Gambini et al., 2015), alginate-CaCl 2 microspheres (Cho et al., 2014), cyclodextrins (Kaur et al., 2015), Gelatin (Karthikeyan et al., 2015), bovine serum albumin (Guo et al., 2015), silk protein (Lozano et al., 2014), and zein (Penalva et al., 2015). ...
Resveratrol (RES) loaded Zein‐SHA (low‐molecular‐weight sodium hyaluronate) nanoparticles with average diameter of about 152.13 nm and polydispersity index (PDI) of 0.122, which can be used to encapsulate, protect and deliver resveratrol. By measuring ABTS free radical scavenging ability and iron (III) reducing power, it was determined that encapsulated resveratrol has higher in vitro antioxidant activity than free resveratrol. When tested with murine breast cancer cells 4T1, the encapsulated resveratrol also showed higher antiproliferative activity than free resveratrol, with IC50 values of 14.73 and 17.84 μg/ml, respectively. The colloidal form of resveratrol developed in this research may be particularly suitable for functional foods and beverages, as well as dietary supplements and pharmaceutical products. Resveratrol nanoparticles with zein as carrier were successfully prepared. RES nanoparticles have better in vitro antioxidant activity and antitumor effect than free resveratrol. RES could be a natural compound for development of nutraceutical and cosmeceutical products.
... (30). The high thermal stability of the complexes was proved by the non-isothermal thermogravimetric analysis conducted in our previous work (29). The analysis also gave evidence of the stoichiometric ratio of host: guest to be 1:1 in the formed complexes. ...
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.
... To synthesize the IC, the ultrasonication method was chosen over the conventional methods because of its various benefits such as higher yields, low reaction time, and ease of operation. 18 Moreover, it utilizes the eco-friendly ultrasonic frequencies rather than conventional heating to perform the reaction. Then, the IC, IC-5, was characterized using various techniques such as ultraviolet (UV)−visible spectroscopy, infrared (IR) spectroscopy, 1 H nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC), and the effect of encapsulation on various properties of compound 4 was investigated. ...
For the first time, inclusion has been crafted between a carbohydrate based molecule and β-CD hydrophobic cavity for the asymmetric catalytic applications. This novel D-glucosamine based inclusion compound has been synthesized in high yields using innovative and proficient acoustic cavitation technology and well characterized by using various techniques, such as IR, NMR, UV, TGA, SEM and other spectroscopic techniques. It was observed that the inclusion of D-glucosamine derivative in hydrophobic cavity of β-CD increased its surface area and thermal stability. This catalytic system worked well in water for direct aldol reaction to afford the products in excellent yields with high diastereo- and enantio-selectivities.
... The structure of β -CD comprises a hydrophobic core with a hydrophilic outer surface. Moreover, the addition of hydroxyl propyl (HP) group to β -CD remarkably enhances its properties like stability, solubility and oral bioavailability 8,9 while maintaining bioactivity and diminishes tissue irritation. It is worth mentioning that the HP derivative of β -CD enhances aqueous solubility by more than 27 fold 9 . ...
There is evidence that the structural modification of curcumin (CUR) into its pyrazole form (CP) and the complexation of CUR with hydroxypropyl beta cyclodextrin (HPβCD) both improve curcumin's chemical–physical properties and enhance its biological activities. However, making use of both strategies is scarce. This study aims at modifying CUR structurally with hydrazine hydrate and the complexation of the modified CUR with HPβCD, employing a simple protocol, which has not been reported so far. The physicochemical structural features of the prepared compounds have been probed through UV-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA) and scanning electron microscopy (SEM). The aqueous solubility of the products was enhanced as examined visibly and by UV-Vis spectroscopy and optical microscopy. The cytotoxicity of the samples in A549 lung cancer cell lines was assessed by MTT assay and cell counting through the trypan blue exclusion method. Negligible colony formation was observed as checked by clonogenic assay in the lung cancer cell lines. Besides being toxic to cancer cell lines, the samples were found to be non-toxic to human peripheral blood mononuclear cells (PBMCs), as revealed by MTT assay.
... In the present work, probe sonication, an extremely efficient, economical and time dipping technique capable of forming ICs [10] (reported in our previous work) has been used to form complexes of BITC with β-CD. Furthermore, complexation with modified β-CD and its detailed thermal studies have also been reported. ...
... UV absorption spectroscopy is an effective method to explore the formation of inclusion complexes (Kaur, Uppal, Kaur, Agarwal, & Mehta, 2015). Besides that, this technique is helpful to show and determine the content of guest molecules in the inclusion complexes (Zhou et al., 2016). ...
Amylose (AM) tends to form single helical inclusion complexes with suitable agents. These complexes are considered promising biomaterial carrier since the guest molecules can be released later, leading to many applications, especially in the pharmaceutical industry. Rifampicin (RIF) has long been recognized as an active drug against Mycobacterium tuberculosis, however, the administration of RIF in high dosages can originate unwanted side-effects. Due to the fact that the use of native amylose (AM) in the formation of complexes is limited by their low water solubility, it was acetylated with a medium degree of substitution (DS), allowing solubilizing (0.5 gL⁻¹) acetylated amylose (AMA) in water at neutral pH, in opposition to that observed with native amylose (trace solubility). The resulting acetylated amylose was characterized by means of Fourier Transform Infrared (FT-IR) spectroscopy and Scanning Electron Microscopy (SEM). FT-IR results indicated that the acetylation of anhydroglucose units of amylose corresponds to a low DS, whereas SEM results suggested that the smooth surfaces of amylose granules were changed into rougher surfaces after acetylation. Ultraviolet absorption spectroscopy (UV–vis) analysis confirmed the formation and allowed the quantification of both native (AM-RIF) and acetylated (AMA-RIF) amylose inclusion complexes. Their characterization in solution was performed by dynamic light scattering (DLS) and zeta potential (ZP) measurements. The average size of inclusion complexes as determined by DLS, ranged between 70 and 100 nm. Besides, ZP analysis showed that both complexes are more stable in the presence of RIF. This study may lead to the development of an effective method for the preparation of amylose inclusion complexes, which is beneficial to their further application in drug delivery systems.
In this work, we studied the formation of supramolecular inclusion complexes (pseudopolyrotaxanes) generated by the interactions between L35 Pluronic (PEO-PPO-PEO triblock copolymer) and hydroxyl propyl-modified cyclodextrins (HP-α-CD and HP-β-CD). The structural characteristics of the L35/CD composites were investigated by X-ray diffraction spectroscopy, which highlighted the effective inclusion of the copolymer. The thermodynamic properties of the pseudopolyrotaxanes were determined through density and speed of sound experiments conducted on aqueous mixtures with various L35/CD compositions, while turbidimetric analyses allowed the investigation of the kinetics of the threading process of L35 polymeric chains within the cavity of the cyclodextrins. Both thermodynamic and kinetic features were explored at various temperatures (20, 25, 30 and 35 °C). According to the negative values of the Gibbs free energies, we observed that the formation of the pseudopolyrotaxanes is spontaneous for both cyclodextrins. Specifically, the inclusion process is more favoured for HP-β-CD. This result was supported by the peculiar effects of the cyclodextrins on the interfacial characteristics of the copolymer at the air/water interface. In conclusion, this paper provides an extensive description of L35/HP-α-CD and L35/HP-β-CD complexes that have potential as thermo-sensitive nanocarriers with controlled release properties.
In this study, cyclodextrin metal-organic framework/chitosan (CD-MOF/CS) nanocapsules, which have a hydrophobic core and a hydrophilic shell, were fabricated as delivery systems for bioactive agents. The nanocapsules were prepared by electrostatic deposition of cationic chitosan onto the anionic CD-MOF core. The presence of the CS coating reduced the mean diameter and polydispersity index of the nanocapsules, which was attributed to their ability to inhibit particle aggregation. Moreover, the encapsulation efficiency of resveratrol within the nanocapsules increased appreciably after coating them with chitosan (from 66.5 to 91.3%). The chitosan coating was also shown to increase the antioxidant activity and photostability of the encapsulated resveratrol. Information about the binding interactions of the resveratrol with the nanocapsules was obtained using fluorescence spectroscopy, infrared spectroscopy, and thermal analysis. The new nanocapsules created in this study may have applications for the encapsulation, protection, and delivery of bioactive agents in food, supplement, and pharmaceutical applications.
The inclusion complexes of Phenanthrene with native βCD and ionic liquid modified βCD were prepared and investigated in both solid and solution states. The formation of the inclusion complexes were successfully monitored by FTIR, TGA, DSC, 1D ¹H NMR, 2D NOESY NMR and UV–vis spectroscopy. The results revealed that Phenanthrene formed 1:1 stoichiometry ratio for both host-guest inclusion complexes with an apparent formation constant of 239.7 M⁻¹ for native β-cyclodextrin, which was higher than ionic liquid modified β-cyclodextrin (14.9 M⁻¹). The NMR studies showed that Phenanthrene penetrated into the cavity of both cyclodextrins (CDs) from the more accessible wider side. For βCD, Phenanthrene displayed one mode of binding, i.e., formation of an inclusion complex. Meanwhile, ionic liquid modified β-cyclodextrin demonstrated two modes of binding, i.e. inclusion in the CD cavities and interaction with the outer surface of the CD molecules, mainly near the ionic liquid (IL) group.
An efficient, eco‐friendly and cost‐effective protocol has been developed for the synthesis of vesamicol, benzovesamicol, spirovesamicol, their analogues and drug molecules such as Naftopidil and SR 59230 A. In this reaction, water has played dual role i. e. of i) bifunctional catalyst and ii) reaction medium. Except reactants, no other chemical reagent/promotor is required to afford the products. Reaction follows 100% atom economy and has been found to be highly chemo‐selective. All studied reactions worked well to yield the corresponding products in excellent to near quantitative yields without following the tedious and time consuming column chromatography as purification step. Thus, this protocol provides the vesamicol and other products without generating any chemical waste to the environment. Furthermore, this methodology has been successfully applied for 15 gm scale also.
In this study, the nano and micro-sized cyclodextrin-based metal-organic frameworks (CD-MOFs) were successfully conducted using short-chain starch nanoparticles as seeds through seed-mediated method. The morphology, size, crystal structure, thermal and N2 adsorption properties of CD-MOFs prepared at different time intervals were investigated. The scanning electron microscopy results showed that the size variation from nanometer to millimeter could be controlled by crystal growth time. The CD-MOFs based on short-chain starch nanoparticle had higher crystallinity and N2 uptake, thus indicating that the method of seed-mediated was more facile and efficient than the previous approach. Resveratrol (Res) is a natural polyphenol compound that has anticancer and antimicrobial activities against several pathogens. However, this compound suffers from poor stability. Trans-Res rapidly isomerizes when exposed under ultraviolet or visible light. The results showed that the stability of Res was substantially enhanced by its encapsulation in CD-MOF crystals.
Resveratrol is a naturally occurring therapeutic molecule used for treatment of diseases caused by oxidative stress. This investigation elucidates the advantages of fabrication of size controlled resveratrol inclusion complex. This has been done by encapsulating resveratrol-cyclodextrin inclusion complex in a phospholipid stabilized nanoemulsion formulated by ultrasonication emulsification method. The prepared nanoemulsion has been compared with resveratrol encapsulated nanoemulsion system. The morphology of the resveratrol nanoemulsion and inclusion complex nanoemulsion have been observed using transmission electron microscopy with average size 20.41 ± 3.41 and 24.48 ± 5.70 nm respectively. The nanoemulsion showed good loading and release efficiency. The radical diminishing potential of resveratrol and its inclusion complex has been compared in nanoemulsion. The effect of UV irradiation (365 nm) on resveratrol in different solvent systems (ethanol, water and nanoemulsion) indicated that nanoemulsion prevents degradation of resveratrol. Efforts have also been made to explore the interactions between bovine serum albumin and resveratrol in nanoemulsion.
The formation of an inclusion complex between 1,2-dihydroxyanthraquinones (1,2-DHAQ) and β-cyclodextrin (β-CD) has been studied by UV-visible, fluorescence spectroscopy and electrochemical methods. The stoichiometric ratio of the inclusion complex was found to be 1 : 1 and the binding constant was evaluated using the Benesi-Hildebrand equation. The peak currents (Ipa and Ipc) change drastically with increasing β-CD concentration and the peak potentials (Epa and Epc) shifted. A mechanism is proposed to explain the inclusion process. A stable solid inclusion complex was prepared using a co-precipitation method and it is characterized by FT-IR, XRD, DSC, SEM, and (1)H NMR that confirmed the formation of the inclusion complex. The β-CD and 1,2-DHAQ inclusion complex obtained by molecular docking studies is in good correlation with the results obtained through experimental methods using PatchDock and FireDock servers. The virtual study of the energetically favorable complex was carried out by PM3 calculations and molecular orbital energy studies suggest that orientation A is more favourable than orientation B.
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.
Amino pyrazole belongs to anti-inflammatory class, and is characterized by a low solubility in water. (In order to increase its solubility in water, inclusion complex of amino pyrazole with β-CD was obtained.) The inclusion complex obtained between AMP and β-cyclodextrin, was characterized by FT-IR, (1)H NMR, (1)H-(1)H NOESY, (13)C NMR, DEPT, XHCOR, spectra, through TG analysis, DTA, DSC and Scanning Electron Microscopy (SEM). The stoichiometry of inclusion complex is 1:1 (guest-host) and K stability is 1.1×10(4)M(-1).
Resveratrol has attracted interest as a wine constituent that may reduce heart disease. Published data on the molar absorptivity and chemical stability of cis- and trans-resveratrol have varied greatly. Accurate values for UV absorbance for trans-resveratrol [UV λmax (EtOH) nm (ε) 308 (30 000)] and cis-resveratrol [UV λmax (EtOH) nm (ε) 288 (12 600)] were determined and are used to improve chromatographic quantitation methods. Trials conducted under a variety of commonly encountered laboratory conditions show that trans-resveratrol is stable for months, except in high-pH buffers, when protected from light. cis-Resveratrol was stable only near pH neutrality when completely protected from light. Keywords: Antioxidant; phenolic; wine; grape; stilbene; isomer; UV spectroscopy; absorptivity
Resveratrol, which occurs in two isomeric forms, trans and cis, is a phytoalexin with numerous pharmacological activities, such as anti-cancer, an-tiviral, neuroprotective and anti-aging. Red wine is the main source of the com-pound and an easy way of including resveratrol in the human diet. In this study, the most popular commercial Serbian wines (red, white and rosé-type) were ana-lyzed for their content of trans-and cis-resveratrol. The analysis was perfor-med by HPLC with a UV detector. Prior to the injection, phenolic compounds were extracted onto a LiChrolut RP18 bonded silica cartridge. The concen-tration of trans-resveratrol ranged from 0.11 to 1.69 mg L -1 and cis-resveratrol from 0.12 to 1.49 mg L -1 .
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.
Cancer is the second leading cause of death in the United States. Despite the estimated 565,650 deaths in 2008 of Americans as a result of cancer, it is mostly a preventable disease. Simply by modification of diet, maintenance of optimum body weight, and regular physical activity, 30% to 40% of all instances of cancer could be prevented. Modification of diet alone by increasing vegetable and fruit intake could prevent 20% or more of all cases of cancer and may potentially prevent approximately 200,000 cancer-related deaths annually. Because of their safety, low toxicity, antioxidant properties, and general acceptance as dietary supplements, fruits, vegetables, and other dietary elements (phytochemicals and minerals) are being investigated for the prevention of cancer. Extensive research over the past several decades has identified numerous dietary and botanical natural compounds that have chemopreventive potential. In this review, we discuss promising natural chemopreventive compounds, their molecular targets, and their mechanisms, which may help the further design and conduct of preclinical and clinical trials.
Resveratrol is a highly polyphenolic substance which possesses extensive physiological activities. However, its application is limited by light instability and poor aqueous solubility. In this paper, resveratrol nanodispersion with high light stability and water dissolution rate was prepared by a combination of antisolvent precipitation in the presence of nontoxic polymer and spray-drying. The active ingredients of the unprocessed raw resveratrol decreased 80 wt% when exposed to sun light directly, while that of the resveratrol nanodispersion only reduced 14 wt% at the same condition. The resveratrol nanodispersion dissolved completely in less than 45 min, while raw resveratrol didn't dissolve completely after 120 min. Meanwhile, resveratrol nanodispersion exhibited better antioxidant activity compared to that of raw resveratrol when added in artificial intestinal juice. This study is helpful to promote the application of resveratrol and provides a routine for enhancing stability and water solubility of photosensitive lipophilic materials.
Awareness of the role that nutraceuticals play in the treatment and prevention of disease has led to an explosion of research in this exciting arena that seems to overflow into the food, cosmetic, nutraceutical, and pharmaceutical industries. Nutrients, supplements and herbal compounds have shown promise as either alternatives to modern medicine or complementary tools in the treatment and prevention of disease. This review provides a brief outlay of the advantages and challenges of nutraceutical delivery via dermatological, oral and ophthalmic routes. Emphasis is directed towards nutraceutical formulation strategies adopted to overcome physicochemical challenges and instability of natural bioactives in order to improve their delivery and bioavailability to the body. This paper highlights how novel techniques have achieved products with greater commercial viability and efficacy than their conventional counterparts. Importance of multicomponent products where individual bioactives potency is not subdued by each other has been marked. Ultimately it is the adoption and merging of the different formulation technologies and prudent scientific validation that will dictate the future success of nutraceuticals. This is especially pertinent in a market where an informed consumer demands an innovative all-in-one product that does not compromise in its results.
The inclusion complex of picoplatin with γ-cyclodextrin (γ-CD) was prepared and characterised by different analytical methods, including NMR, FTIR, TGA, phase solubility as well as SEM. All of these approaches indicated that picoplatin was able to form an inclusion complex with γ-CD, and that the picoplatin/γ-CD inclusion compounds exhibited different spectroscopic features and properties from free picoplatin. The stoichiometry of the complex was 1:1; the pyridine group of picoplatin was deeply inserted into the cavity of γ-CD and the amine platinum group of picoplatin was near the narrower rim of γ-CD. The calculated apparent stability constant of the complex was 10,318M(-1). Moreover, the water solubility of picoplatin was significantly improved, according to phase-solubility studies. The complex maintained its anticancer activity, as shown by an in vitro cell-survival assay on A549 and MCF-7 cancer cell lines. All of these results showed that inclusion complexation may be a promising strategy to design a novel formulation of picoplatin as an anticancer therapy.
2,4-Dinitrophenol (2,4-DNP), 2,4-dinitroaniline (2,4-DNA), 2,6-dinitroaniline (2,6-DNA) and 2,6-dinitrobenzoic acid (2,6-DNB) has appeared for the UV absorption bands in different wavelength region below 400nm, a combination of these dinitro aromatic compounds gave the broad absorption spectra within the UV region. The absorption intensities have been increased by preparation of the inclusion complex of dinitro compounds with β-cyclodextrin (β-CD). Prepared inclusion complexes are used to improve the UV protection properties of the ball point pen ink against photo degradation. The formation of solid inclusion complexes was characterized by FT-IR, and (1)H NMR spectroscopy. The UV protecting properties of these inclusion complexes were calculated their sun protection factor (SPF) is also discussed. The stability of the ballpoint pen ink has been confirmed by UV-Visible spectroscopic method.
Curcumin (Cur) is a hydrophobic polyphenol with diverse pharmacological effects, especially for cancer treatment. However, its weak water solubility and stability was the major obstacle for the formulation research of Cur. The complexation of Cur and hydroxypropyl-β-cyclodextrin (HP-β-CD) were done by grinding. The increasing solubility of Cur was achieved due to complexation and the photochemical stability of Cur was improved. The inclusion of Cur could happen when two ends of Cur were embedded into the cavity of the HP-β-CD rings. The in-situ hydrogels (ISGs) of Cur and its inclusion complexes were prepared using poloxamers 407 and 188 as the matrix. The extent of drug's in-vitro release from the ISGs depended on the dissolution of drugs. Both of the ISGs had transdermal effect and cytotoxicity on B16-F10 cells. However, the effects of the ISGs containing Cur inclusion complexes were much higher than those of Cur ISGs because of the improved Cur solubility in the former. The cytotoxicity of Cur on melanoma cells was related to blocking of cellular proliferation in the G2/M stage followed by cellular apoptosis. The ISGs of Cur inclusion complexes are a promising formulation for melanoma treatment.
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.
The formation of host–guest inclusion complex of 2,4-dinitroaniline (2,4-DNA) with nano-hydrophobic cavity of β-cyclodextrin (β-CD) in solution phase were studied by UV–visible spectrophotometer and electrochemical method (Cyclic Voltammetry, CV). The prototropic behaviors of 2,4-DNA with and without β-CD was studied by spectrophotometrically. The binding constant of the inclusion complex at 303 K was calculated using Benesi–Hildebrand plot and thermodynamic parameter (ΔG) were also calculated. The inclusion complex formation between β-CD and 2,4-DNA was confirmed by 1H NMR, 2D ROESY NMR, FT-IR, XRD and SEM analysis. The 2,4-DNA:β-CD inclusion complex was obtained by molecular docking studies and it was good correlation with the results obtained through experimental methods.
β-Cyclodextrin (β-CD), which is widely used to increase the stability, solubility, and bioavailability of guests, can form host-guest inclusion complexes with a wide variety of organic molecules. In this study the β-CD/soybean lecithin inclusion complex was prepared. The effect of reaction parameters such as reaction temperature, reaction time and the molar ratio of β-CD/soybean lecithin on inclusion ratio were studied. The inclusion ratio of the product prepared under the optimal conditions of β-CD/soybean lecithin molar ratio 2:1, reaction temperature 60°C reaction time 2h was 40.2%. The results of UV-vis, DSC, XRD and FT-IR spectrum indicated the formation of inclusion complex. The thermal stability experiment indicated that the thermal stability of soybean lecithin in inclusion complex was significantly improved compared with free soybean lecithin.
Plants possess a wide range of molecules capable of improve healing: fibre, vitamins, phytosterols, and further sulphur-containing compounds, carotenoids, organic acid anions and polyphenolics. However, they require an adequate level of protection from the environmental conditions to prevent losing their structural integrity and bioactivity. Cyclodextrins are cyclic oligosaccharides arising from the degradation of starch, which can be a viable option as encapsulation technique. Cyclodextrins are inexpensive, friendly to humans, and also capable of improving the biological, chemical and physical properties of bioactive molecules. Therefore, the aim of this review is to highlight the use of cyclodextrins as encapsulating agents for bioactive plant molecules in the pharmaceutical field.
The inclusion complexation behavior, characterization and binding ability of sulfadimethoxine (SDMO) with α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD) have been investigated both in solution and solid state by means of absorption, fluorescence, time-resolved fluorescence, (1)H NMR, FT-IR, DSC, SEM, TEM, XRD and molecular modeling methods. The spectral shifts revealed that the part of pyrimidine and aniline rings of SDMO are entrapped in the CD cavity. The stoichiometric ratio and association constant were determined by Benesi-Hildebrand plots and spectroscopic studies respectively. FT-IR spectroscopy was used to compare inclusion systems with physical mixtures, and demonstrated the complex formation in the solid state. The morphology and size of the nanoparticles of SDMO/CD complexes in aqueous solution were observed by TEM. The DSC analysis showed that the thermal stability of SDMO was enhanced in the presence of CD. Investigations of energetic and thermodynamic properties by PM3 method confirmed the stability of the inclusion complexes.
The aim of this study was to improve the water solubility of barbigerone by complexing it with hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexation behavior, characterization and interactions of barbigerone with HP-β-CD were investigated in both solution and the solid state by means of UV/VIS, (1)H NMR, FT-IR, PXRD, SEM. All the characterization information demonstrated the formation of barbigerone-HP-β-CD (bar-HP-β-CD) inclusion complex, and the bar-HP-β-CD inclusion compounds exhibited different spectroscopic features and properties from barbigerone. The results demonstrated that the water solubility of barbigerone was notably increased in the presence of HP-β-CD. Furthermore, preliminary in vitro cytotoxicity assay showed that bar-HP-β-CD still maintain the anticancer activity of barbigerone. These results suggest that HP-β-CD will be potentially useful in the delivery of water-insoluble anticancer agents such as barbigerone.
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.
Interaction between bovine serum albumin (BSA) and resveratrol (RES) included by β-cyclodextrin (β-CD) in Tris–HCl aqueous buffer solutions (pH 7.4) has been investigated by isothermal titration calorimetry (ITC) combined with ultraviolet, fluorescence and circular dichroism spectra analyses. The results indicate that there are two classes of ligand binding sites. The first class of binding is mainly driven by enthalpy, while the second one is driven by both enthalpy and entropy. The secondary structure of BSA in the aqueous system was slightly changed with addition of the drug. Thermodynamic parameters, i.e., equilibrium constants, standard enthalpy changes and the entropy effects for the binding process of RES with BSA were calculated based on the calorimetric data. In fact, due to the poor solubility of RES in aqueous buffer medium, these parameters could not be determined by the employed experimental method without the existence of the CD.
The formation of resveratrol–cyclodextrin inclusion complexes in aqueous solutions has been characterized using the hydroperoxidase activity of lipoxygenase as the enzymatic system. The addition of cyclodextrins to the reaction medium had an inhibitory effect on resveratrol oxidation by lipoxygenase due to the complexation of phytoalexin into the cyclodextrin cavity, which is in equilibrium with free cyclodextrins and free resveratrol, the only effective substrate for lipoxygenase. This inhibitory effect depends on the complexation constant Kc between resveratrol and the type of cyclodextrins used. In the present work β- and G2-β-cyclodextrins were used and their Kc were calculated by nonlinear regression of the inhibition curves obtained in the presence of cyclodextrins. The values obtained were 4317 and 5130M−1 for β- and G2-β-cyclodextrin, respectively, values which were checked and confirmed by the “cyclodextrin assay”.
The study describes an improved version of the reverse-phase-HPLC method. To determine free resveratrol isomers, the method uses isocratic elution and electrochemical detection with the use of a glassy working electrode at a potential of 0.75 V. The effects of important factors – such as the isomerization of standard resveratrol solution in diffused daylight and its dependence on temperature or resveratrol isomerization in wine samples – were investigated. The equilibrium between trans- and cis-isomer was achieved after a 5-h exposure to the daily diffused light and it was not significantly influenced by the temperature (30–60 °C). Linearity was obtained in the concentration range from 0.01 to 10 mgl−1. The detection limit (S/N=3) was 3 μgl−1 for trans-resveratrol and 15 μgl−1 for cis-resveratrol. The trans- and cis-resveratrol were determined in selected Czech red and white wines and in the extract from Vitis vinifera plant. The concentration of trans-resveratrol ranged from 0.7 to 11 mgl−1, that of cis-resveratrol from 0.6 to 5.1 mgl−1.
Cyclodextrins (CYDs) are cyclic non-reducing oligosaccharides built up from six, seven or eight glucopyranose units (α-, β- or γ-CYD, respectively). Many drugs are able to form an inclusion complex with CYDs, being trapped entirely or at least partially into their slightly apolar cavities. Complexes of CYDs and salbutamol were obtained in both the liquid and solid state. The influence of both temperature and CYD concentration on complex solubility was studied using the method of Higuchi and Connors (Adv. Anal. Chem., 4 (1965) 117–212). This is based on monitoring changes in the solubility of substrate (salbutamol) on the addition of complexing agents (α-, β-, Me-β- and γ-CYD). The rate of increase in substrate solubility with CYD concentration varied with the type of CYD used (Me-β->β-⪢γ->α-CYD). As salbutamol is water soluble and an AL type diagram is obtained, the solid complex was prepared by freeze-drying (lyophilization). In order to confirm solid complex formation, differential scanning calorimetry (DSC) was used. When guest molecules are incorporated in the CYD cavity, their melting, boiling or sublimation points usually shift to a different temperature or disappear within the temperature range where the CYD is decomposed. The thermograms obtained showed an endothermic peak for the freeze-dried salbutamol and for the physical mixture (salbutamol and β-CYD both freeze-dried) which was eliminated for the inclusion complex.
Thermal effects of inclusion processes of α-, β-, γ- and Mβ-cyclodextrin with resveratrol (RES) in aqueous solutions were determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity at the temperature of 298.15K. Standard enthalpy changes, stoichiometry and equilibrium constants of the inclusion complexes were derived from the direct calorimetric data utilizing nonlinear simulation. The thermodynamic parameters were discussed in the light of weak interactions between the host and the guest molecules combining with UV spectral message. The results indicate that all of the complexes formed in the aqueous solutions are in 1:1 stoichiometry. The binding processes of α-, β- and Mβ-cyclodextrin with the guest are mainly driven by enthalpy, while that of γ-cyclodextrin with the drug is driven by both enthalpy and entropy.
Sulforaphane (SF) is an anticancer agent present naturally in widely consumed cruciferous vegetables, and it can easily be decomposed by heat, oxygen and alkaline conditions. In order to enhance stability of SF, the inclusion complex of SF with hydroxypropyl-β-cyclodextrin (HP-β-CD) was prepared successfully using co-precipitation method and the inclusion ratio was found to be 1:1. The results showed that the stability of the inclusion complex against heat, oxygen and alkaline conditions was greatly enhanced compared with that of SF. Furthermore, FTIR, 1H NMR and UV/visible spectroscopy were performed to prove the formation of the inclusion complex SF/HP-β-CD. Therefore, it is a very effective method to maintain the anticancer and antioxidant function of SF by preparing the inclusion complex SF/HP-β-CD.
The U.S. Congress, in the Dietary Supplement Health and Education Act (DSHEA) established a framework for regulation of dietary supplements by the U.S. Food and Drug Administration. For dietary supplements, the FDA regulates labeling to limit health claims, but is not empowered to insist on rigorous studies establishing safety before marketing (as would be required for drugs or food additives). This creates a substantial potential risk to the health of the public, and serious adverse effects have been reported from some dietary supplements that are currently being marketed. The author recommends that a new category of dietary supplements, called "nutraceuticals," be established for supplements to be administered at doses that exceed normal human exposure to these agents in foods. Regulations should require that these nutraceuticals be judged safe before they are marketed.
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.
An inclusion complex of β-cyclodextrin with carvedilol was prepared by using a convenient new method of microwave irradiation. Phase-solubility studies demonstrated the ability of β-cyclodextrins to complex with carvedilol and increase drug solubility. The structure of inclusion complex was determined by fluorescence spectroscopy and 1H NMR, 13C NMR measurements in solution. The solid inclusion was characterised by infrared spectroscopy, differential scanning calorimetry (DSC) and element analysis. These experimental results confirmed the existence of 1:2 inclusion complex of carvedilol with β-cyclodextrin, the formation constant of complex was determined by the fluorescence method. Molecular modeling predicted the energy-minimized structure of the complex.
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.
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.
P4VPy(DBSA)x complexes (x = 0.25, 0.50, 0.75, or 1.00 DBSA/P4VPy repeat units) are able to form inclusion complexes with three cyclodextrins (CDs). The complexes were characterized by XRD, XPS, 13C CP/MAS NMR, 1H NMR, DSC, and TGA. A columnar structure with poor order is established in all the inclusion complexes. XPS studies show that the interaction between DBSA and P4VPy is affected by inclusion complexation when the DBSA content is high (x ≥ 0.5), resulting in the expulsion of some DBSA ions from the polymer chain and reprotonation. TGA shows that the initial decomposition temperatures of the inclusion complexes are lower than those of the CDs and the pristine complexes, a result different from that of the linear chain polymer−cyclodextrin ICs. DSC measurements indicate that the inclusion of the side chains within CDs makes the P4VPy main chain much stiffer, thereby raising the glass transition temperature. 1H NMR measurements also suggest that interactions between CDs and the side chains of P4VPy(DBSA)x complexes are present even in DMSO solution. However, the mesomorphic layer structures of P4VPy(DBSA)x complexes are destroyed upon the formation of inclusion complexes with CDs.
The slightly water-soluble cancer chemopreventive polyphenol resveratrol (Res) and its inclusions with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-CD) have been investigated. The stoichiometric ratios and stability constants have been determined by phase-solubility measurements. In all cases 1:1 complexes are formed. The inclusion ability of HP-CD is larger than that of β-CD. The antioxidant activity of the Res complexes has been determined by the scavenging of the stable radical DPPH. The scavenging capacity of the two complexes increases with increasing concentration of cyclodextrins. Res/HP-CD complex shows a higher scavenging capacity than Res/β-CD complex. The antioxidant activity of Res in free form has little difference with Res in complexed form at the same concentration.
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.
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 >1.0mg/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.
Copyright © 2007 Elsevier Ltd. All rights reserved.
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.
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.
Liposoluble vitamins (A, D, E, and K) and carotenoids have many benefits on health. They are provided mainly by foods. At pharmacological doses, they can also be used to treat skin diseases, several types of cancer or decrease oxidative stress. These molecules are sensitive to oxidation, thus encapsulation might constitute an appropriate mean to preserve their properties during storage and enhance their physiological potencies. Formulation processes have been adapted for sensitive molecule, limiting their exposure to high temperature, light or oxygen. Each administration pathway, oral, systemic, topical, transdermal and local, requires different particle sizes and release profile. Encapsulation can lead to greater efficiency allowing smaller administration doses thus diminishing potential hypervitaminosis syndrome appearance and side effects. Carrier formulation can be based on vitamin dissolution in lipid media and its stabilization by surfactant mixture, on its entrapment in a matrix or molecular system. Suitability of each type of carrier will be discussed for each pathway.
Differential scanning calorimetry (DSC) combined with a curve-fitting program was utilized to quantitatively determine the polymorphic composition of famotidine in the compacts prepared by different compression treatments. Two types of famotidine compacts (compact I or II) were prepared by compressing a conical shape or a flattened shape of powder bed of famotidine form B. The compact I was constructed by a transparent region in the center with an opaque region surrounded outside, but the compact II was formed by a whole opaque region only. A drilled disc sample was prepared and then directly determined by DSC analysis. The Raman spectral results clearly indicate that all the compacts whether in any region before DSC determination were only of famotidine form B and independent of compression pressure applied. Under DSC determination, however, the curve-fitted relative compositions of form B in the drilled disc I sample were gradually reduced to 23-24% with the increase of compression pressure, whereas the curve-fitted relative composition of form A was slowly increased up to 76-77%. A transitional phase of famotidine form B (form B*) in the transparent region of the compact I after applying >150 kg/cm(2) of compression pressure was easily detected, and then transformed to famotidine form A under DSC heating process. But this transitional phase and polymorphic transformation of famotidine could not be detected by other spectroscopic methods. This suggests that the DSC heating system was a preferred method not only to quantitatively analyze the polymorphic transformation of famotidine but also to find a newly transitional phase of famotidine in the compressed compact.
The discovery of thousands of new marine natural products over the past two decades has been spurred by findings of potent bioactivity. In recent years it has become apparent that many such compounds have affinities for certain cellular receptors in the mammalian cell, functional properties that may also play a part in the largely unknown roles of these compounds in their respective parent organisms. Our work in marine natural products has led to the discovery of compounds with significant activity in several assays with importance in understanding fundamental cellular processes and treatment of human disease states. We present recent work on the isolation of new bioactive compounds from marine invertebrates with profound activity on mammalian and non-mammalian receptors.
Designer foods provide benefits for both consumers and the food-processing industry, and represent a significant opportunity for biotechnology companies. But are they also blurring the definition of a drug?
About 30% of the worldwide sales of drugs are based on natural products. Though recombinant proteins and peptides account for increasing sales rates, the superiority of low-molecular mass compounds in human diseases therapy remains undisputed mainly due to more favorable compliance and bioavailability properties. In the past, new therapeutic approaches often derived from natural products. Numerous examples from medicine impressively demonstrate the innovative potential of natural compounds and their impact on progress in drug discovery and development. However, natural products are currently undergoing a phase of reduced attention in drug discovery because of the enormous effort which is necessary to isolate the active principles and to elucidate their structures. To meet the demand of several hundred thousands of test samples that have to be submitted to high-throughput screening (HTS) new strategies in natural product chemistry are necessary in order to compete successfully with combinatorial chemistry. Today, pharmaceutical companies have to spend approximately US $350 million to develop a new drug. Currently, approaches to improve and accelerate the joint drug discovery and development process are expected to arise mainly from innovation in drug target elucidation and lead finding. Breakthroughs in molecular biology, cell biology, and genetic engineering in the 1980 s gave access to understanding diseases on the molecular or on the gene level. Subsequently, constructing novel target directed screening assay systems of promising therapeutic significance, automation, and miniaturization resulted in HTS approaches changing the industrial drug discovery process drastically. Furthermore, elucidation of the human genome will provide access to a dramatically increased number of new potential drug targets that have to be evaluated for drug discovery. HTS enables the testing of an increasing number of samples. Therefore, new concepts to generate large compound collections with improved structural diversity are desirable.
The supramolecular interaction of curcumin and beta-cyclodextrin (beta-CD) has been studied by spectrophotometry. The mechanism of the inclusion was studied and discussed based on the variations of pK(a), absorption intensity, and infrared spectrograms. The results show that beta-CD reacts with curcumin to form a 2:1 host-guest complex with an apparent formation constant of 5.53 x 10(5) mol(-2) x L2. Based on the enhancement of the absorbance of curcumin produced through complex formation, a spectrophotometric method for the determination of curcumin in bulk aqueous solution in the presence of beta-CD was developed. The linear relationship between the absorbance and curcumin concentration was obtained in the range of 0-15 microg/mL, with a correlation coefficient (r) of 0.9991. The detection limit was 0.076 microg/mL. The proposed method was used to determine the curcumin in curry and mustard with satisfactory results.
Norfloxacin is a special compound. Its hydrate form seems to be more soluble in water than in the anhydrate form. To investigate the hydration behavior of norfloxacin, the moisture-sorption analysis of anhydrous norfloxacin in different humidities was determined by using differential scanning calorimetry and thermogravimetric analysis. The contents of free water and bound water in the moisture-equilibrated norfloxacin were estimated quantitatively by using a curve-fitting program. Fourier transform infrared microspectroscopy with or without thermal analyzer was used to examine the structural change and dehydration process of norfloxacin in different humidities. The result indicates that the water content sorbed to anhydrous norfloxacin changed lightly below 51% relative humidity (RH) but increased markedly beyond 51% RH. The content of free water in the moisture-equilibrated norfloxacin was nearly to zero below 55% RH, but increased dramatically in high humidity. The content of bound water also enhanced gradually with the external humidity and reached to a constant of one unit after > 75% RH. When norfloxacin anhydrate transformed to its hydrate, the infrared peak intensity at 1732 and 1253 cm(-1) assigned to the C=O and C-O groups of carboxylic acid decreased gradually with the increase of water content, but the infrared peak intensity at 1584 and 1339 cm(-1) corresponding to asymmetric and symmetric carboxylates increased. Furthermore, the peak at 2553 cm(-1) assigned to the NH(+)(2) also appeared clearly and shifted from 2558 cm(-1) in higher water content and humidity. The main functional groups of norfloxacin changed from COOH to COO(-) and NH to NH(+)(2), attributable to the proton transfer from COOH group to NH group. This suggests that the hydration can induce the interaction between norfloxacin molecules from hydrogen bonding to ionic bonding by a proton-transfer process in the solid state.
Cyclodextrin complexes of the natural compound curcumin were prepared in order to improve the water solubility and the hydrolytic and photochemical stability of the compound. Complex formation resulted in an increase in water solubility at pH 5 by a factor of at least 10(4). The hydrolytic stability of curcumin under alkaline conditions was strongly improved by complex formation, while the photodecomposition rate was increased compared to a curcumin solution in organic solvents. The cavity size and the charge and bulkiness of the cyclodextrin side-chains influenced the stability constant for complexation and the degradation rate of the curcumin molecule.