Curcumin Solution Research Articles

Abstract B23: Curcumin suppresses the growth and metastasis of prostate cancer cells by downregulation of SKP2.

Abstract Purpose: Prostate Cancer (PCa) is the second leading cause of cancer-related deaths in American men. The morbidity and mortality to PCa are 2.39-fold higher in African American men as compared to Caucasian males. Aberrant overexpression of SKP2 is frequently found in human cancers including prostate cancer, but little is known about pharmacological compounds targeting Skp2 activity. This study investigated inhibitory effects of curcumin (diferuloylmethane) on malignant features of prostate cancer cells in vitro and xenograft mouse models in vivo, and mechanistically on Skp2 level. Design Methods: Prostate cancer cells (PC3) and mouse prostate cancers cells (MPC3) in culture were treated with curcumin solution for indicated periods of time in vitro. Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were used to determine mRNA and protein expression of Skp2 in cancer cells. Cell proliferation, colony formation, and invasion assay were compared between curcumin-treated and control cells. Mouse prostate cancer cells were injected into immunodeficient mice followed with curcumin administration (200mg/kg/day). Tumorigenesis was analyzed in curcumin-treated and control mice after 20 days. Results: Curcumin treatment of PC3 cells resulted in a significant reduction of cell proliferation, soft agar transformation and invasion as compared to controls. Curcumin treatment led to a decrease of Skp2 level through a reduction of Skp2 mRNA and a shortened half-life of Skp2 protein. As expected, p27 protein, a major downstream target of Skp2, was increased upon curcumin treatment, whereas c-Myc protein level was not affected by curcumin treatment in prostate cancer cells. MPC3 cells, administered into immunodeficient mice via tail vein or orthotopic implantation, developed lung metastasis or enlarged prostate tumors, respectively. Importantly, cancer progression was significantly suppressed by curcumin treatment. A reduced level of Skp2 protein and induction of cell senescence were detected in tumors of curcumin-treated mice, but not in tumors of control mice. Conclusion: Our results indicated that curcumin suppresses both the tumor growth in mouse prostates and distant metastasis of prostate cancer cells in lung by inhibiting Skp2 level. Citation Format: Yuanying Gong, Wenfu Lu, Yingqiu Xie, Qing Yang, Robert J. Matusik, Zhenbang Chen. Curcumin suppresses the growth and metastasis of prostate cancer cells by downregulation of SKP2. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B23.

T.P.10 The acute effects of curcumin exposure on skeletal muscle contractile function

Curcumin is a component in the Asian spice turmeric which has demonstrated anti-inflammatory, anti-oxidant and anti-cancer effects in animal models of human disease. It has also been shown to alleviate the dystropathology in mdx mice. However, in vitro studies on isolated sarcoplasmic reticulum (SR) vesicles indicate that curcumin has inhibitory effects on SR function which may adversely affect muscle contraction. The aim of this study was to investigate the specific effects of curcumin on skeletal muscle contractile function. These experiments, conducted on isolated extensor digitorum longus (EDL) muscles from 8week old ARC mice, were approved by the animal ethics committee of the University of Western Australia. Mice were anaesthetized (pentobarbitone, 40mg/kg, IP) and the muscles surgically removed and mounted in an in vitro muscle test system containing mammalian Ringer solution bubbled with carbogen. Measures of contractile function were performed before and after 60min exposure to either 100μM curcumin (dissolved in DMSO) or control solution containing the equivalent DMSO concentration (0.05%). The effect of curcumin on the susceptibility to and recovery from fatigue was also assessed. Curcumin exposure significantly decreased maximum specific force in EDL muscles by 14% compared to control muscles exposed to DMSO alone (curcumin: 19.7±0.7N/cm2, n=6; control: 23.0±1.0N/cm2, n=6, P<0.05). Curcumin had no significant effect on peak twitch force, the time to peak or the 1/2 relaxation time of twitch contractions. The rate of muscle fatigue was significantly reduced after curcumin exposure compared to controls (P<0.01, n=6). This study shows for the first time that (100μM) curcumin exposure significantly affects skeletal muscle contractile function. As the twitch contraction and relaxation times are sensitive to changes in SR function, these results are not consistent with previous findings that curcumin inhibits SR Ca2+ handling in SR vesicles.

Enhanced dissolution performance of curcumin with the use of supersaturatable formulations

The goal of this research was to employ formulation strategies to develop supersaturatable formulations for curcumin, a poorly water-soluble drug to improve the in vitro dissolution performance. Self-emulsifying lipid-based formulations and hydrophilic carrier formulations with polymeric precipitation inhibitors were designed to achieve supersaturation upon dilution. In vitro dissolution of curcumin from each formulation was performed, in addition to assessment of the utility of polymers such as polyvinylpyrrolidone (PVP), hydroxypropyl methyl cellulose (HPMC) as precipitation inhibitors. For the hydrophilic solvent formulation, it was observed that the presence of 10% w/w polymer results in curcumin concentrations almost 100-fold greater compared to the formulation without the polymer. Incorporation of polymer in the SEDDS formulation results in a supersaturated solution of curcumin with concentrations identical to the theoretical starting dose. The high drug concentrations were sustained for 3 h as compared to the self-emulsifying formulation without the polymer. The low dissolution of curcumin in the neat hydrophilic solvent and self-emulsifying formulation is attributed to the uncontrolled precipitation of the drug upon mixing with the dissolution media, which is a result of formation of an unstable supersaturated solution. Upon relative assessment, the rank order in which the polymers inhibited precipitation was PVP-K30 < PVP-K90 < HPMC.

ApoE3 mediated polymeric nanoparticles containing curcumin: Apoptosis induced in vitro anticancer activity against neuroblastoma cells

Curcumin, a natural phytoconstituent, is known to be therapeutically effective in the treatment of various cancers such as, breast cancer, lung cancer, pancreatic cancer, brain cancer, etc. However, low bioavailability and photodegradation of curcumin hampers its overall therapeutic efficacy. Anionic polymerization method was employed for the preparation of apolipoprotein-E3 mediated curcumin loaded poly(butyl)cyanoacrylate nanoparticles (ApoE3-C-PBCA) and characterized for size, zeta potential, entrapment efficiency, photostability, morphology, and in vitro release study. ApoE3-C-PBCA were found to be effective against SH-SY5Y neuroblastoma cells compared to curcumin solution (CSSS) and curcumin loaded PBCA nanoparticles (C-PBCA) from in vitro cell culture investigations. Flow cytometry techniques employed for the detection of anticancer activity revealed enhanced activity of curcumin against SH-SY5Y neuroblastoma cells with ApoE3-C-PBCA compared to CSSS and C-PBCA, and apoptosis being the underlying mechanism. Present study revealed that ApoE3-C-PBCA has tremendous potential to develop into an effective therapeutic treatment modality against brain cancer.

Fabrication and characterization of curcumin‐releasing silk fibroin scaffold

Here, we report the fabrication of a curcumin-releasing porous silk fibroin scaffold by simple mixing of fibroin solution (aqueous) with curcumin solution (organic) followed by freeze-thaw of the mixture. The scaffold has a uniform pore distribution with an average pore size of ~115 μm and a degree of swelling of 2.42% and water uptake capacity of 70.81%. Fibroin showed thermal stability up to ~280°C, whereas encapsulated curcumin disintegrated at ~180°C. Fourier transform infrared, powder X-ray diffraction, and nuclear magnetic resonance studies together with UV-visible and fluorescence spectroscopy investigations revealed the solvent (which was used to dissolve curcumin) induced conformational transition of fibroin from silk-I to silk-II that led to the formation of water-stable structure. Fluorescence spectroscopy data also suggested the presence of hydrophobic domains in fibroin and encapsulation of curcumin in such domains through hydrophobic interactions. Release kinetics and mathematical modeling studies indicated a slow and sustained release profile with diffusion as the predominant mode of release. Further, in vitro anticancer, antioxidant, and antimicrobial assays suggested that the biological activity of encapsulated curcumin remains unaltered. The fabrication process is simple, reproducible, and does not require any sophisticated instruments or toxic crosslinking agents. It is anticipated that the curcumin-loaded fibroin scaffold could be used in soft tissue replacements including localized postsurgical chemotherapy against tumors, dressing material for quick healing of wounds and burns, and other related applications.

Binding and stabilization of curcumin by mixed chitosan–surfactant systems: A spectroscopic study

Abstract The effect of the biopolymer chitosan, in presence of a cationic surfactant, viz., cetyl trimethyl ammonium bromide (CTAB) and a non-ionic surfactant, viz., polyoxyethylene (20) sorbitan monooleate (TW80) on the solubility and spectroscopic properties of the bioactive compound curcumin has been studied at physiological pH (7.4) condition. Based on the solvent and medium sensitive absorption and fluorescence properties of curcumin, the apparent binding constants of curcumin to chitosan, chitosan–CTAB and chitosan–Tween-80 systems have been estimated. From the fluorescence quenching by potassium iodide and acrylamide of the chitosan entrapped curcumin solutions, it has been found that curcumin is non-uniformly distributed in the colloidal chitosan solution. Curcumin is located mostly inside the hydrophobic interior of chitosan while a small fraction resides in the cationic centres of chitosan. The stability provided to curcumin by chitosan alone and in the presence of CTAB and TW80 has been investigated by spectrophotometric analysis of the kinetics of degradation of curcumin. It has been observed that the reaction rate constants were decreased in various systems in the order: chiotsan-TW80 > chitosan–CTAB > chitosan. The interaction of curcumin with chitosan has been found to be exothermic and driven by hydrophobic interactions, hydrogen bond formation, and electrostatic interactions.

Preparation of Curcumin-Loaded Liposomes and Evaluation of Their Skin Permeation and Pharmacodynamics

This study aimed to investigate the in vitro skin permeation and in vivo antineoplastic effect of curcumin by using liposomes as the transdermal drug-delivery system. Soybean phospholipids (SPC), egg yolk phospholipids (EPC), and hydrogenated soybean phospholipids (HSPC) were selected for the preparation of different kinds of phospholipids composed of curcumin-loaded liposomes: C-SPC-L (curcumin-loaded SPC liposomes), C-EPC-L (curcumin-loaded EPC liposomes), and C-HSPC-L (curcumin-loaded HSPC liposomes). The physical properties of different lipsomes were investigated as follows: photon correlation spectroscopy revealed that the average particle sizes of the three types of curcumin-loaded liposomes were 82.37 ± 2.19 nm (C-SPC-L), 83.13 ± 4.89 nm (C-EPC-L), and 92.42 ± 4.56 nm (C-HSPC-L), respectively. The encapsulation efficiency values were found to be 82.32 ± 3.91%, 81.59 ± 2.38%, and 80.77 ± 4.12%, respectively. An in vitro skin penetration study indicated that C-SPC-L most significantly promoted drug permeation and deposition followed by C-EPC-L, C-HSPC-L, and curcumin solution. Moreover, C-SPC-L displayed the greatest ability of all loaded liposomes to inhibit the growth of B16BL6 melanoma cells. Therefore, the C-SPC-L were chosen for further pharmacodynamic evaluation. A significant effect on antimelanoma activity was observed with C-SPC-L, as compared to treatment with curcumin solution in vivo. These results suggest that C-SPC-L would be a promising transdermal carrier for curcumin in cancer treatment.

Photoinactivation of Staphylococcus epidermidis biofilms and suspensions by the hydrophobic photosensitizer curcumin – Effect of selected nanocarrier: Studies on curcumin and curcuminoides XLVII

Solubilization and stabilization from rapid degradation by the use of nanocarriers are necessary to exploit curcumin’s phototoxic potential towards pathogenic bacteria. However, maintenance of the phototoxicity requires a careful selection of type and amount of nanocarrier. The phototoxicity of an aqueous supersaturated curcumin solution without nanocarrier was compared to that of curcumin solubilized in polyethylene glycol 400 (PEG 400), Pluronic® F 127 (F 127) and hydroxypropyl-γ-cyclodextrin (HPγCD) on Staphylococcus (S.) epidermidis biofilms and suspensions. The nanocarriers stabilized the hydrophobic photosensitizer (PS) towards physical precipitation and hydrolytic degradation; however, photobleaching was pronounced (46–100% degradation) after irradiation with a dose of ∼9J/cm2 blue light depending on selected nanocarrier. Complete inactivation of S. epidermidis in suspension was achieved after exposure of ∼5J/cm2 combined with curcumin in 20% PEG 400 and 0.5% HPγCD and less than 1J/cm2 light in case of a supersaturated curcumin solution. Curcumin in 1.5% F 127 induced phototoxicity towards bacterial biofilms; however, it was not phototoxic towards planktonic S. epidermidis. All curcumin preparations investigated demonstrated significant and similar phototoxicity towards biofilms (13–29% bacterial survival). A ∼9J/cm2 light dose was not sufficient to eradicate S. epidermidis biofilm completely under the current conditions.

Pulmonary Administration of a Water-Soluble Curcumin Complex Reduces Severity of Acute Lung Injury

Local or systemic inflammation can result in acute lung injury (ALI), and is associated with capillary leakage, reduced lung compliance, and hypoxemia. Curcumin, a plant-derived polyphenolic compound, exhibits potent anti-inflammatory properties, but its poor solubility and limited oral bioavailability reduce its therapeutic potential. A novel curcumin formulation (CDC) was developed by complexing the compound with hydroxypropyl-γ-cyclodextrin (CD). This results in greatly enhanced water solubility and stability that facilitate direct pulmonary delivery. In vitro studies demonstrated that CDC increased curcumin's association with and transport across Calu-3 human airway epithelial cell monolayers, compared with uncomplexed curcumin solubilized using DMSO or ethanol. Importantly, Calu-3 cell monolayer integrity was preserved after CDC exposure, whereas it was disrupted by equivalent uncomplexed curcumin solutions. We then tested whether direct delivery of CDC to the lung would reduce severity of ALI in a murine model. Fluorescence microscopic examination revealed an association of curcumin with cells throughout the lung. The administration of CDC after LPS attenuated multiple markers of inflammation and injury, including pulmonary edema and neutrophils in bronchoalveolar lavage fluid and lung tissue. CDC also reduced oxidant stress in the lungs and activation of the proinflammatory transcription factor NF-κB. These results demonstrate the efficacy of CDC in a murine model of lung inflammation and injury, and support the feasibility of developing a lung-targeted, curcumin-based therapy for the treatment of patients with ALI.

Preparation and in vivo pharmacokinetics of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles

Background:Curcumin (CUR) has been linked with antioxidant, anti-inflammatory, antimicrobial, anti amyloid, and antitumor effects, but its application is limited because of its low aqueous solubility and poor oral bioavailability.Methods:To improve its bioavailability and water solubility, we synthesized two series of poly (ε-Caprolactone)-poly (ethylene glycol)-poly (ε-Caprolactone) triblock copolymers by ring-opening polymerization of poly (ethylene glycol) and ε-Caprolactone, with stannous 2-ethylhexanoate as the catalyst. Structure of the copolymers was characterized by proton nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, and gel permeation chromatography. The nanoparticles (NPs) were prepared using a probe-type ultrasonic emulsion and solvent evaporation method. To obtain an optimal delivery system, we explored the effect of the length of the copolymers’ hydrophilic and hydrophobic chains on the encapsulation of hydrophobic CUR, performing entrapment efficiency and drug loading evaluations, as well as studying the particle distribution and in vitro release using the direct dispersion method. Finally, study of the in vivo pharmacokinetics of the CUR-loaded NPs was also carried out on selected copolymers in comparison with CUR solution formulations.Results:CUR was encapsulated with 94.3% and 95.5% efficiency in biodegradable nanoparticulate formulations based on NP43 and NP63, respectively. Dynamic laser light scattering and transmission electron microscopy indicated a particle diameter of 55.6 nm and 62.4 nm for NP43 and NP63, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry analysis of the NPs showed that CUR was encapsulated into the NPs. The in vitro release experiments showed that NP63 controlled the release of CUR more effectively, with only 55% of CUR released after 96 hours. In comparison with the free-drug solution in vivo, encapsulation of the CUR in NP63 increased mean residence time from 0.169 to 40.148 hours and the area under the concentration–time curve 4.178-fold.Conclusion:CUR was effectively entrapped by the prepared NPs, which could improve the solubility of CUR and prolong its retention in the systemic circulation.

Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route

In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

Binding of Curcumin to Senile Plaques and Cerebral Amyloid Angiopathy in the Aged Brain of Various Animals and to Neurofibrillary Tangles in Alzheimer's Brain

The binding of curcumin to senile plaques (SPs) and cerebral amyloid angiopathy (CAA) was examined in the aged brain of various animal species and a human patient with Alzheimer's disease (AD), together with its binding to neurofibrillary tangles (NFTs). Brain sections were immunostained with anti-amyloid β protein 1-42 (Aβ42) and anti-amyloid β protein 1-40 (Aβ40) antibodies. These sections were also stained with alkaline Congo red, periodic acid-methenamine silver (PAM), and curcumin (0.009% curcumin solution) with or without formic acid pretreatment. The sections from the AD brain were also immunostained for anti-paired helical filament-tau (PHF-tau), and were stained with Gallyas silver for NFTs. Some SPs in the AD, monkey, dog, bear, and amyloid precursor protein transgenic mouse (APP Tg-mouse) brains contained congophilic materials, and were intensely positive for curcumin. In addition, curcumin labeled some diffuse SPs negative for Congo red in the AD, monkey, bear, and APP Tg-mouse brains. In all animals, CAA was intensely positive for both Congo red and curcumin. The specific curcumin staining activity was lost by formic acid pretreatment. In the AD brain, NFTs positive for PHF-tau and Gallyas silver were moderately stained with curcumin. These findings indicate that curcumin specifically binds to the aggregated Aβ molecules in various animals, and further to phosphorylated tau protein, probably according to its conformational nature.

Physical characterization and cellular uptake of propylene glycol liposomes in vitro

In order to facilitate the intracellular delivery of therapeutic agents, a new type of liposomes–propylene glycol liposomes (PGL) were prepared, and their cell translocation capability in vitro was examined. PGL was composed of hydrogenated egg yolk lecithin, cholesterol, Tween 80 and propylene glycol. With curcumin as a model drug, characterization of loaded PGL were measured including surface morphology, particle size, elasticity, encapsulation efficiency of curcumin and physical stability. Using curcumin-loaded conventional liposomes as the control, the cell uptake capacity of loaded PGL was evaluated by detection the concentration of curcumin in cytoplasm. Compared with conventional liposomes, PGL exhibited such advantages as high encapsulation efficiency (92.74% ± 3.44%), small particle size (182.4 ± 89.2 nm), high deformability (Elasticity index = 48.6) and high stability both at normal temperature (about 25°C) and low temperature at 4°C. From cell experiment in vitro, PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution. Little toxic effect on cellular viability was observed by methyl tetrazolium assay. In conclusion, PGL might be developed as a promising intracellular delivery carrier for therapeutic agents.

Lung-targeted delivery system of curcumin loaded gelatin microspheres

The purpose of the study is to design and evaluate curcumin loaded gelatin microspheres (C-GMS) for effective drug delivery to the lung. C-GMS was prepared by the emulsification-linkage technique and the formulation was optimized by orthogonal design. The mean encapsulation efficiency and drug loading of the optimal C-GMS were 75.5 ± 3.82 % and 6.15 ± 0.44%, respectively. The C-GMS presented a spherical shape and smooth surface with a mean particle diameter of 18.9 μm. The in vitro drug release behavior of C-GMS followed the first-order kinetics. The tissue distribution showed that the drug concentrations at lung tissue for the C-GMS suspension were significantly higher than those for the curcumin solution, and the Ce for lung was 36.19. Histopathological studies proved C-GMS was efficient and safe to be used as a passive targeted drug delivery system to the lung. Hence, C-GMS has a great potential for the targeted delivery of curcumin to the lung.

Effect of curcumin on the expression of high mobility group box 1 and apoptotic neurons in hippocampus after global cerebral ischemia reperfusion in rats

To explore the effects of curcumin on the expression of high mobility group box 1 (HMGB1) and apoptotic neurons in hippocampus after global cerebral ischemia/reperfusion in SD rats. A total of 192 male SD rats were randomly divided into 4 groups: sham group (SH), ischemia-reperfusion group (IR), curcumin group (Cur) and solvent control group (SC). Bilateral vertebrate arteries were electrocauterized and bilateral common carotid arteries liberated in 3 ischemic groups. Isasteric curcumin solutions (200 mg/kg) or menstruum were injected intraperitoneally at 1 hour pre-ischemia in Cur and SC groups. The rats in each group were ligated for 15 minutes and then decapitated at 1, 3, 5 and 7 d post-reperfusion respectively. Cell morphology was observed on hematoxylin & eosin-stained slides. Apoptotic neurons were detected in CA1 region by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Western blot was used to make a semi-determination of HMGB1 expression. At each time point, the number of apoptotic neurons was much more in IR and SC groups than that in SH group (P < 0.05). And the number of apoptotic neurons at 1, 3, 5, 7 d post-reperfusion was only 41%, 57%, 65% and 70% in Cur group respectively (P < 0.05). The expressional level of HMGB1 in IR and SC groups was significantly lower at 1d post-reperfusion (0.685 ± 0.050; 0.695 ± 0.053 vs 0.977 ± 0.063, P < 0.05). And it was significantly higher at 3, 5, 7 d post-reperfusion in IR and SC groups than that in SH groups (1.360 ± 0.045/1.353 ± 0.045; 1.342 ± 0.046/1.338 ± 0.047; 1.319 ± 0.052/1.322 ± 0.035 vs 0.992 ± 0.031; 0.978 ± 0.090; 0.992 ± 0.075, P < 0.05). The level at 1 d post-reperfusion (0.842 ± 0.063) in Cur group was significantly higher than that in IR and SC groups but lower than that in SH group. And it was lower at 3, 5, 7 d post-reperfusion (1.125 ± 0.023, 1.098 ± 0.073, 1.087 ± 0.089) than those in IR and SC groups (P < 0.05). There was no significant difference of HMGB1expression level between IR and SC groups. The expression level of HMGB1 in hippocampus is significantly reduced at 1 d post-reperfusion. Then it significantly increases and a high level is maintained until 7 d after global cerebral ischemia/reperfusion. Curcumin can reduce hippocampal neuronal apoptosis and injury. Such an effect may be due to an inhibition of the synthesis and release of HMGB1.

Study binding of Al–curcumin complex to ds-DNA, monitoring by multispectroscopic and voltammetric techniques

In this work a complex of Al 3+ with curcumin ([Al(curcumin) (EtOH) 2](NO 3) 2) was synthesized and characterized by UV–vis, FT-IR, elemental analysis and spectrophotometric titration techniques. The mole ratio plot revealed a 1:1 complex between Al 3+ and curcumin in solution. For binding studies of this complex to calf thymus-DNA various methods such as: UV–vis, fluorescence, circular dichroism (CD), FT-IR spectroscopy and cyclic voltammetry were used. The intrinsic binding constant of ACC with DNA at 25 °C was calculated by UV–vis and cyclic voltammetry as 2.1 × 10 4 and 2.6 × 10 4, respectively. The thermodynamic studies showed that the reaction is enthalpy and entropy favored. The CD results showed that only the Δ-ACC interacts with DNA and the Δ-ACC form has not any tendency to interact with DNA, also the pure curcumin has not any stereoselective interaction with CT-DNA. Fluorimetric studies showed that fluorescence enhancement was initiated by a static process in the ground state. The cyclic voltammetry showed that ACC interact with DNA with a binding site size of 2. From the FT-IR we concluded that the Δ-ACC interacts with DNA via partial electrostatic and minor groove binding. In comparison with previous works it was concluded that curcumin significantly reduced the affinity of Al 3+ to the DNA.

Study on Spectroscopic and Dyeing Characteristics of Curcumin on Poly(lactic acid) and Poly(ethylene terephthalate) Fabrics

This research aimed to study the use of curcumin as a natural dye for dyeing poly(lactic acid) and poly(ethylene terephthalate) fabrics. The study found that curcumin was dyeable on PLA and PET, providing a brilliant yellow color on the fabric. Curcumin could build up very well on PLA, while lower build up was on PET. At the same applied concentration, higher color yield was observed on the dyed PLA fabric. To achieve the same visual color yield, a significantly lower concentration of curcumin was required for PLA as compared with PET. The color shade of curcumin-dyed PLA differed from the PET analogue. A bathochromic shift of the K/S curve was found when the substrate was changed from PLA to PET. The influence of polymer media on the spectroscopic properties of curcumin could be elucidated by measuring absorbance properties of curcumin in ethyl acetate and methyl benzoate, being representatives of PLA and PET, respectively. At the same concentration, curcumin solution in ethyl acetate exhibited higher absorbance than that in methyl benzoate, corresponding to the deeper shade obtained when dyed on PLA as compared with PET. Bathochromic shift of absorbance curve was also observed when the solvent was changed from ethyl acetate to methyl benzoate.

Exercise Training and Antioxidants

We have investigated the cardioprotective effects of exercise training and/or curcumin on lead acetate-induced myocardial damage. Forty rats were randomly divided into 5 groups: (1) lead acetate, (2) curcumin, (3) endurance training, (4) training + curcumin, (5) sham groups. The rats in groups 3 and 4 experienced the treadmill running of 15 to 22 m/min for 25 to 64 minutes, 5 times a week for 8 weeks. Groups 1 to 4 received lead acetate (20 mg/kg), the sham group received curcumin solvent (ethyl oleat), and the curcumin and training + curcumin groups received curcumin solution (30 mg/kg) intraperitoneally. Lead administration resulted in significant increases in high-sensitivity C-reactive protein (hs-CRP), creatine kinase-MB (CK-MB), malondialdehyde (MDA), and low-density lipoprotein (LDL), and significantly decreased glutathione peroxidase (GPx), Total Antioxidant Capacity (TAC), and high-density lipoprotein (HDL) levels. Treadmill running and\or curcumin supplementation resulted in a significant decrease in hs-CRP, CK-MB, MDA, and LDL levels and significantly increased GPx, TAC, and HDL levels. These results suggest a lifestyle-induced cardioprotective potential in ameliorating lead-induced cardiotoxicity.

Curcumin-loaded PLGA-PEG-PLGA triblock copolymeric micelles: Preparation, pharmacokinetics and distribution in vivo

The aim of this study was to assess the potential of new copolymeric micelles to modify the pharmacokenetics and tissue distribution of Curcumin (CUR), a hydrophobic drug. In the present study, a poly (d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PLGA-PEG-PLGA) copolymer was synthesized and characterized by (1)H NMR, gel permeation chromatography and FTIR analysis. The CUR-loaded PLGA-PEG-PLGA micelles were prepared by dialysis method and the physicochemical parameters of the micelles such as zeta potential, size distribution and drug encapsulation were characterized. The pharmacokinetics and biodistribution of CUR-loaded micelles in vivo were evaluated. The results showed that the zeta potential of CUR-loaded micelles was about -0.71mV and the average size was 26.29nm. CUR was encapsulated into PLGA-PEG-PLGA micelles with loading capacity of 6.4±0.02% and entrapment efficiency of 70±0.34%. The plasma AUC((0-)(∞)), t(1/2α), t(1/2β) and MRT of CUR micelles were increased by 1.31, 2.48, 4.54 and 2.67 fold compared to the CUR solution, respectively. The biodistribution study in mice showed that the micelles decreased drug uptake by liver and spleen and enhanced drug distribution in lung and brain. These results suggested that PLGA-PEG-PLGA micelles would be a potential carrier for CUR.

Preparation and characterization of intravenously injectable curcumin nanosuspension

The interest in nanosuspensions by the pharmaceutical industry is increasing given several nanosuspension products currently on the market for poorly soluble drugs. In this study, a novel dosage form for curcumin (CUR), CUR nanosuspension (CUR-NS), was successfully prepared by high pressure homogenization to improve CUR’s cytotoxicity, as well as improve its application via intravenous injection. Characterization of the CUR-NS was evaluated by morphology, size, zeta potential, solubility, dissolution rate, and crystal state of drug. The nanoparticles for CUR-NS presented a sphere-like shape under transmission electron microscopy with an average diameter of 250.6 nm and the zeta potential of CUR-NS was −27.92 mV. Solubility and dissolution rate of CUR in the form of CUR-NS were significantly increased due to the small particle size and the crystalline state of CUR was preserved to increase its stability against degradation. Superior cytotoxicity in Hela and MCF-7 cells was obtained for CUR-NS compared with CUR solution. The safety evaluation showed that, compared with the CUR solution, CUR-NS provided less local irritation and phlebitis risks, lower rate of erythrocyte hemolysis. These findings suggest that CUR-NS may represent a promising new drug formulation for intravenous administration in the treatment of certain cancers.