Curcumin In Aqueous Solution Research Articles

Phosphorylated walnut protein isolate as a nanocarrier for enhanced water solubility and stability of curcumin

The low solubility and poor dispersion of alkaline-extracted walnut protein isolate (AWPI) limit its application as a protein-based carrier for the delivery of poorly soluble nutraceuticals, including curcumin. This work investigated the physicochemical characteristics of phosphorylated walnut protein isolate (PWPI) extracted using sodium tripolyphosphate (STP) and evaluated its encapsulation ability. The results of phosphorus determination, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) spectroscopy confirmed the phosphorylation of the extracted PWPI. Circular dichroism (CD) analysis indicated that PWPI contained higher α-helix and lower β-sheet contents than AWPI. The PWPI prepared at pH 9.0 and 11.0 showed significantly improved solubility, similar surface hydrophobicity, and increased surface charges compared to the AWPI. Fluorescence quenching experiments indicated that the binding affinity of curcumin to PWPI was significantly higher than that of AWPI. When bound to PWPI, the solubility of curcumin in aqueous solution was greatly enhanced, with an 8,700-fold increase at a nanocomplex concentration of 10 mg/mL. The complexation of curcumin with PWPI significantly improved the storage stability of curcumin. Additionally, the PWPI-curcumin nanocomplexes showed significantly increased antioxidant capacity. Phosphorylated walnut protein isolate showed greatly improved solubility and strong encapsulation ability, making it a promising nanocarrier for curcumin. This article is protected by copyright. All rights reserved.

Formulation of Glycyrrhizic Acid-based Nanocomplexes for Enhanced Anti-cancer and Anti-inflammatory Effects of Curcumin.

In this study, nanocomplexes composed of glycyrrhizic acid (GA) derived from the root of the licorice plant (Glycyrrhiza glabra) were formulated for the delivery of curcumin (CUR). Sonication of amphiphilic GA solution with hydrophobic CUR resulted in the production of nanosized complexes with a size of 164.8 ± 51.7 nm, which greatly enhanced the solubility of CUR in aqueous solution. A majority of the CURs were released from these GA/ CUR nanocomplexes within 12 h. GA/CUR nanocomplexes exhibited excellent intracellular uptake in human breast cancer cells (Michigan cancer foundation-7/multi-drug resistant cells), indicating enhanced anti-cancer effects compared to that of free CUR. In addition, GA/CUR nanocomplexes demonstrated high intracellular uptake into macrophages (RAW264.7 cells), consequently reducing the release of the pro-inflammatory cytokine tumor necrosis factor-α. Furthermore, GA/CUR nanocomplexes successfully reduced the levels of serum pro-inflammatory cytokines and splenomegaly in a rheumatoid arthritis model.

Preparation, characterization and antioxidant properties of curcumin encapsulated chitosan/lignosulfonate micelles

In this work, chitosan/lignosulfonate composite micelles (CS-LS) were successfully prepared through polyelectrolyte self-assembly. Curcumin was encapsulated in CS-LS to obtain CUR-CS-LS. The results showed that the average diameter of CS-LS and CUR-CS-LS were 239 nm and 286 nm, respectively. The results show that the aromatic rings of lignosulfonate are assembled into the hydrophobic core of micelles through π–π interactions, and chitosan binds outside the hydrophobic core as a hydrophilic shell through electrostatic interactions. Curcumin is encapsulated in the hydrophobic core through hydrophobic interactions. Encapsulation improves the thermal stability and pH stability of curcumin. Compared with free curcumin, the retention efficiency of curcumin in CUR-CS-LS increased by approximately 6.66 and 6.46 times under the same heat treatment and pH conditions, respectively. Encapsulation also increases the antioxidant activity of curcumin in aqueous solution. In addition, the release mechanism of curcumin is diffusion and matrix swelling. These findings explain that CS-LS may be an effective promising delivery system for encapsulating hydrophobic biologically active substances.

Binding of metal ions to the curcumin mediated methoxy polyethylene glycol thiol conjugated greenly synthesized gold nanoparticles: A fluorescence spectroscopic study

Curcumin, a nontoxic molecule obtained from plant extract, was used to reduce gold salt to produce gold nanoparticles (AuNPs). First time the particles were functionalized with methoxy polyethylene glycol thiol (mPEGT), which acts as a stabilizing agent in such a manner that the methoxy group is pointed toward the aqueous solution to serve as anchor point to many metal ions. The greenly synthesized gold nanoparticles have a size between ∼40 and ∼83 nm. The prepared material was characterized in detail by SEM, XRD, TGA and FT-IR spectroscopy. These AuNPs were found to be fluorescence active similar to free curcumin suggesting that curcumin is conjugated at the surface of AuNPs. Exposure of the mPEGT functionalized AuNPs to different concentrations of metal cations in the range between 0 and 100 μM resulted in the decrease in the fluorescence intensity of the AuNPs unlike free curcumin in aqueous solution. Excited state lifetime measurements further validated quenching mechanism to be static in nature. The binding constant and number of binding sites for such interaction were evaluated. Based on observed bimolecular quenching rate constants, kQ values, the order of association of the metals studied is Pb (II) > Hg (II) >Hg (I) > Cd (II)>Al (III) >Ni (II) >Cu (II) >Na2HAsO4. These interactions between the mPEGT conjugated AuNPs and the metal ions in solution contribute a proof-of-concept that mPEGT functionalized curcumin mediated AuNPs can be used as a simple, cheap and straightforward, on-site detection system for toxic and even essential metal ions in solution.

Characteristics and antitumor activity of polysorbate 80 curcumin micelles preparation by cloud point cooling

Curcumin is a natural bioactive compound with known potential for cancer treatment and prevention. However, a major barrier for clinical application is its poor solubility and bioavailability. Nanotechnology is an effective approach to enhance the bioavailability of insoluble drugs. We explored a novel way to prepare micellar curcumin in the common food additive, polysorbate 80, by utilizing the process of micelle formation that occurs during slow cooling below its cloud point. Curcumin molecules were thus dissolved and encapsulated. Micellar curcumin was stable during storage and was more tolerant to harsh pH conditions than free curcumin. The ~20 nm-sized nanocurcumin micelles showed improved antitumor effect than free curcumin in SUM149 human breast cancer xenografts in mice. This new method overcame the difficulty of dissolving curcumin in aqueous solution of polysorbate 80, and may find application in the production of other functional nutraceuticals.

Insight on the chelation of aluminum(III) and iron(III) by curcumin in aqueous solution

In this work we have studied the complexation of curcumin (HCur, 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) with Al(III) and Fe(III) at 37 °C and in 0.16 M NaCl. The protonation constant of curcumin was also determined to evaluate the competition of the ligand for the metal cations and H+. Speciation profiles obtained by potentiometric titrations show that in aqueous solution a complexation occurs at 1:1 ligand-to-cations ratio. With the aim to define the coordination sites of curcumin with these metal ions a mass spectrometry and UV–Vis spectroscopy characterization was carried out. It was found that aluminum binds to the keto-enol moiety of curcumin, while iron binds to the guaiacol (2-methoxyphenol) one. This unexpected experimental evidence was supported by a thorough computational study.

Synthesis of non-ionic and enzyme-responsive bolaamphiphiles for drug delivery applications

Nanoscale drug delivery systems devised from biocompatible and biodegradable molecules with functional groups which are readily amenable to external stimuli, have become a promising approach to circumvent the pitfalls associated with the hydrophobic drugs concomitant with the amplification of drugs’ action. Taking the cognizance of advantages offered by nanostructures and also in search of amphiphiles with intended biomedical applications, a novel and elite family of amphiphilic system that can self-assemble into enzyme-responsive supramolecular architectures has been synthesized via a chemo-enzymatic approach using an immobilized enzyme (lipase) from Candida antarctica (Novozym 435) and employing biocompatible starting materials, i.e. p-hydroxybenzoic acid, monomethoxypolyethyleneglycol (mPEG), and glycerol. The aggregation behavior of the resulting bolaamphiphiles have been studied using critical aggregation concentration and dynamic light scattering measurements, further supplemented by cryogenic transmission electron microscopic studies. The developed amphiphiles render efficient solubilization of model hydrophobic drugs and dyes, e.g. Nile red, nimodipine, and curcumin in aqueous solution. Moreover, the results demonstrate that a subtle structural modulation of the amphiphilic system alters the transportation behavior of the guest molecule. The investigation of the enzyme-responsive behavior of the synthesized bolaamphiphiles using a hydrolase enzyme, Candida antarctica lipase reveals that amide based nanocarriers disassemble and release the encapsulated cargo on incubation with the enzyme. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay unravels negligible cytotoxicity of the bolaamphiphiles at the tested concentrations, indicating their relevance in the development of nanocarriers for biomedical applications.

Co-delivery of hydrophilic and hydrophobic drugs by micelles: a new approach using drug conjugated PEG–PCLNanoparticles

Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG–PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by 1H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG–PCL(DOX–mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31 ± 3.32 and 78.15 ± 3.14%, respectively. The results revealed that the micelles formed by the DOX–mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134 nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG–PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.

Influence of clay minerals on curcumin properties: Stability and singlet oxygen generation

Curcumin (CUR) has showed promising photophysical properties regarding to biological and chemical sciences. However, the main barrier for those applications are their low solubility and stability in aqueous solution. The effects of two different clay minerals, the montmorillonite (SWy-2) and the Laponite RD (Lap) nanoclay, on the stabilization of Curcumin were investigated. Their effects were compared with two well-established environments (acidic and neutral aqueous media). CUR/clay hybrids were prepared using a simple and fast method, where CUR solution was added into clay suspensions, to obtain well dispersed hybrids in water. The degradation process of CUR and CUR/clays hybrids was investigated using UV–Vis spectroscopic. For both studied hybrids, the CUR degradation process was suppressed by the presence of the clay particles. Furthermore, the Lap showed a great stabilization effect than SWy-2. This behavior was due to the smaller particle size and higher exfoliation ability of Lap, providing a large surface for CUR adsorption compared to SWy-2. The degradation process of CUR solutions and CUR/clay hybrids was also studied in the presence of light. CUR photodegradation process was faster not only in the aqueous solution but also in the clay suspension compared to those studied in the dark. The presence of clay particles accelerated the photodegradation of CUR due to the products formation in the reactions between CUR and oxygen radicals. Our results showed that the singlet oxygen quantum yield (ΦΔ) of CUR were about 59% higher in the clay suspensions than CUR in aqueous solution. Therefore, the formation of CUR/clay hybrids, in particularly with Lap, suppressed the degradation in absence light of CUR and increased the singlet oxygen generation, which makes this hybrids of CUR/clay a promising material to enlarge the application of CUR in the biological sciences.

Cyanine-Curcumin Assembling Nanoparticles for Near-Infrared Imaging and Photothermal Therapy.

Near-infrared (NIR) imaging and photothermal therapy (PTT) based on the multifunctional cyanine dyes has shown great promise for cancer therapy. However, most of the PTT agents are often limited by low drug loading, short circulation time, and low biocompatibility. Herein, we developed cyanine-curcumin assembling nanoparticles (CCNPs) via a single-step reprecipitation method. IR-780-C4 (Cyc4) was employed as a photothermal and NIR imaging agent. Self-assembly of Cyc4 and curcumin in aqueous solution could be performed in the absence of surfactants or adjuvants, which is a simple and efficient way to fabricate nanomedicine with high drug loading. Formed CCNPs showed monodispersity, good stability in physiological conditions, and lower cytotoxicity. Moreover, CCNPs possess the high loading (70%) of cyanine dyes and a higher photothermal conversion efficacy than free Cyc4, which contribute to a decrease in the application dosage of cyanine dyes in cancer therapy. Importantly, CCNPs exhibited excellent NIR imaging capacity and photothermal tumor ablation under laser irradiation in vitro and in vivo. This work highlights the potential of using self-assembling of drug molecules to develop functional nanoparticles for drug delivery and cancer therapy.

Effect of Vesicle-to-Micelle Transition on the Interactions of Phospholipid/Sodium Cholate Mixed Systems with Curcumin in Aqueous Solution.

The role of vesicle-to-micelle transition has been investigated in the interactions of phospholipid vesicles, phospholipid/sodium cholate (NaC) mixed vesicles, and phospholipid/NaC mixed micelles with curcumin in aqueous solution. The addition of NaC causes phospholipid vesicles to transit into phospholipid/NaC mixed vesicles and phospholipid/NaC mixed micelles. Turbidity measurement reveals that the presence of curcumin increases the NaC concentration for the solubilization of phospholipid vesicles, which indicates that the bound curcumin tends to suppress the vesicle-to-micelle transition. The pyrene polarity index and curcumin fluorescence anisotropy measurements suggest that phospholipid/NaC mixed micelles have a more compact structure than that of phospholipid vesicles and phospholipid/NaC mixed vesicles. Curcumin associated with phospholipid vesicles, phospholipid/NaC mixed vesicles, and phospholipid/NaC mixed micelles often results in higher intensities of absorption and fluorescence than those of free curcumin. However, phospholipid/NaC mixed vesicles lead to the highest values of absorption and fluorescence intensities, binding constant, and radical-scavenging capacity with curcumin. The different structures in the phospholipid bilayer of phospholipid/NaC mixed vesicles and the hydrophobic part of phospholipid/NaC mixed micelles where curcumin located are discussed to explain the interaction behaviors of phospholipid/NaC mixed systems with curcumin.

Modulation of stability and functionality of a phyto-antioxidant by weakly interacting metal ions: curcumin in aqueous solution

Metal exchange process in metallo–curcumin leading to duality in action: enhancement of both aqueous stability and anti-oxidant property.

The Sensitive Fluorimetric Method for the Determination of Curcumin Using the Enhancement of Mixing Micelle

It is found that the fluorescence of curcumin is greatly enhanced by La3+ in the prescence of sodium dodecyl benzene sulfonate (SDBS). Based on this, a sensitive fluorimetric method for the determination of curcumin in aqueous solution is proposed. In the HOAc-NaOAc buffer, the fluorescence intensity of curcumin is proportional to the concentration of curcumin in the range of 0.0074-7.4μg·mL-1 and the detection limit is 3.66ng·mL-1. The actual samples are satisfactorily determined.

Interactions of cationic trimeric, gemini and monomeric surfactants with trianionic curcumin in aqueous solution

Interactions of trianionic curcumin (Cur(3-)) with a series of cationic surfactants, monomeric surfactant dodecyl trimethylammonium bromide (DTAB), dimeric surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (12-6-12) and trimeric surfactant tri(dodecyldimethylammonioacetoxy)diethyltriamine trichloride (DTAD), have been investigated in aqueous solution of pH 13.0. Surface tension and spectral measurements indicate that the cationic surfactants display a similar surfactant concentration dependent interaction process with Cur(3-), involving three interaction stages. At first the three cationic surfactants electrostatically bind on Cur(3-) to form the surfactant-Cur(3-) complex. Then the bound and unbound cationic surfactants with Cur(3-) aggregate into surfactant-Cur(3-) mixed micelles through hydrophobic interactions above the critical micelle concentration of the surfactants (CMCC) in the presence of Cur(3-). Finally excess unbound surfactants self-assemble into micelles like those without Cur(3-). For all the three surfactants, the addition of Cur(3-) only decreases the critical micelle concentration of 12-6-12 but does not affect the critical micelle concentration of DTAB and DTAD. As the oligomeric degree of surfactants increases, the intermolecular interaction of the cationic surfactants with Cur(3-) increases and the surfactant amount needed for Cur(3-) encapsulation decreases. Compared with 12-6-12, either the weaker interaction of DTAB with Cur(3-) or stronger interaction of DTAD with Cur(3-) limits the stability or solubility of Cur(3-) in surfactant micelles. Therefore, gemini surfactant 12-6-12 is the best choice to effectively suppress Cur(3-) degradation at very low concentrations. Isothermal titration microcalorimetry, surface tension and (1)H NMR results reveal that 12-6-12 and Cur(3-) form a (12-6-12)2-Cur(3-) complex and start to form micelles at extremely decreased concentrations, where either 12-6-12 or Cur(3-) works as a bridge linkage and the resultant structure exhibits the characteristics of oligomeric surfactants.

Curcumin Loaded Nano Globules for Solubility Enhancement: Preparation, Characterization and Ex Vivo Release Study

Curcumin in spite of being an effective chemotherapeutic agent against different type of cancer, suffer from the problem of low systemic bioavailability due to low aqueous solubility, extensive intestinal metabolism and first-pass metabolism when administered via the oral route. The aim of present investigation was to evaluate the potential of nano globules based nanoemulsion formulation for the solubility enhancement of curcumin. The nano globules based formulation was developed using Labrafac Lipophile WL 1349, Unitop FFT 40, PEG 400 and distilled water as an oil, surfactant, co-surfactant and aqueous phase respectively using aqueous titration method. Furthermore, different formulations were subjected to physical stability and consequently evaluated for ex vivo permeation using small intestine. The optimized formulation had small average globule diameter of 58 nm with zeta potential of -32 mv which indicated long-term dispersion stability. The globules were spherical in shape as observed by Transmission electron microscopy. During ex vivo study, the release of curcumin from nanoemulsion was 96.21% and 98.1% in 6 h and 12 h respectively whereas CU suspension was release up to 28.2% at the end of 12 h. This indicated the enhancement of solubility of curcumin in aqueous solution which is the rate limiting step in the absorption of curcumin in the intestine.

The photo- and electrophysical properties of curcumin in aqueous solution

An investigation of the photo- and electrophysical properties of curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) revealed well-defined color changes upon the addition of Hg(2+) or OH(-). Curcumin exhibited high selectivity for Hg(2+) ions, as compared with Cu(2+), Fe(2+), Fe(3+), Zn(2+), Na(+) and Ni(2+) ions in DMSO/H(2)O (5:1, v/v) which was attributed to the formation of a 4:1 Hg(2+)-curcumin coordination complex. Spectral responses at lambda(max)=434nm revealed that curcumin can function as a NOR logic gate with OH(-) and Hg(2+) as input variables. The electrochromic properties of curcumin were studied using an ITO/curcumin-Bu(4)NClO(4)/ITO cell. The electrochromic cell colored red at 3V, but changed to yellow in open-circuit condition.

Fluorescence enhancement effect for the determination of curcumin with yttrium(III)—curcumin—sodium dodecyl benzene sulfonate system

It is found that the fluorescence of curcumin is greatly enhanced by yttrium(III) (Y 3+) in the presence of sodium dodecyl benzene sulfonate. Based on this, a sensitive fluorimetric method for the determination of curcumin in aqueous solution is proposed. In the potassium hydrogen phthalate (KHP) buffer, the fluorescence intensity of curcumin is proportional to the concentration of curcumin in the range of 7.37×10 −4–0.18, 0.18–2.95 μg mL −1 and the detection limit is 0.1583 ng mL −1. The actual samples are satisfactorily determined. In addition, the interaction mechanism is also studied.

The Sensitive Fluorimetric Method for the Determination of Curcumin Using the Enhancement of Mixed Micelle

Curcumin (C21H20O6) is a natural antioxidant, which is considered to be a very useful compound in health matters, and is employed in the treatment of cardiovascular and arthritic illnesses. It is found that the fluorescence of curcumin is greatly enhanced by mixed micelle of sodium dodecyl benzene sulfonate (SDBS) and cetyltrimethylammonium bromide (CTAB) surfactants. Based on this, a sensitive fluorimetric method for the determination of curcumin in aqueous solution is proposed. In the HOAc-NaOAc buffer, the fluorescence intensity of curcumin is proportional to the concentration of curcumin in the range of 0.00020-0.74 microg/mL and the detection limit is 0.017 ng/mL. The synthetic and actual samples are satisfactorily determined. In addition, the interaction mechanism is also studied.

Determination of acidity constants of curcumin in aqueous solution and apparent rate constant of its decomposition

The stability of curcumin (H 3Cur) in aqueous media is improved when the systems in which it is present are at high pH values (higher than 11.7), fitting a model describable by a pseudo-zero order with a rate constant k′ for the disappearance of the Cur 3− species of 1.39 (10 −9) M min −1. There were three acidity constants measured for the curcumin as follows: p K A3=10.51±0.01 corresponding to the equilibrium HCur 2−=Cur 3−+H +, a p K A2=9.88±0.02 corresponding to the equilibrium H 2Cur −=HCur −2+H +. These p K A values were attributed to the hydrogen of the phenol part of the curcumin, while the p K A1=8.38±0.04 corresponds to the equilibrium H 3Cur=H 2Cur −+H + and is attributed the acetylacetone type group. Formation of quinoid structures play an important role in the tautomeric forms of the curcumin in aqueous media, which makes the experimental values differ from the theoretically calculated ones, depending on the conditions adopted in the study.

Inhibition of lipoxygenase 1 by phosphatidylcholine micelles-bound curcumin.

Curcumin (diferuloyl methane) from rhizomes of Curcuma longa L. binds to phosphatidylcholine (PC) micelles. The binding of curcumin with PC micelles was followed by fluorescence measurements. Curcumin emits at 490 nm with an excitation wavelength of 451 nm after binding to PC-mixed micelles stabilized with deoxycholate. Curcumin in aqueous solution does not inhibit dioxygenation of fatty acids by Lipoxygenase 1 (LOX1). But, when bound to PC micelles, it inhibits the oxidation of fatty acids. The present study has shown that 8.6 microM of curcumin bound to the PC micelles is required for 50% inhibition of linoleic acid peroxidation. Lineweaver-Burk plot analysis has indicated that curcumin is a competitive inhibitor of LOX1 with Ki of 1.7 microM for linoleic and 4.3 microM for arachidonic acids, respectively. Based on spectroscopic measurements, we conclude that the inhibition of LOX1 activity by curcumin can be due to binding to active center iron and curcumin after binding to the PC micelles acts as an inhibitor of LOX1.