Solubility In Aqueous Solvents Research Articles

Optimizing Axial and Peripheral Substitutions in Si-Centered Naphthalocyanine Dyes for Enhancing Aqueous Solubility and Photoacoustic Signal Intensity.

Photoacoustic imaging using external contrast agents is emerging as a powerful modality for real-time molecular imaging of deep-seated tumors. There are several chromophores, such as indocyanine green and IRDye800, that can potentially be used for photoacoustic imaging; however, their use is limited due to several drawbacks, particularly photostability. There is, therefore, an urgent need to design agents to enhance contrast in photoacoustic imaging. Naphthalocyanine dyes have been demonstrated for their use as photoacoustic contrast agents; however, their low solubility in aqueous solvents and high aggregation propensity limit their application. In this study, we report the synthesis and characterization of silicon-centered naphthalocyanine dyes with high aqueous solubility and near infra-red (NIR) absorption in the range of 850-920 nm which make them ideal candidates for photoacoustic imaging. A series of Silicon-centered naphthalocyanine dyes were developed with varying axial and peripheral substitutions, all in an attempt to enhance their aqueous solubility and improve photophysical properties. We demonstrate that axial incorporation of charged ammonium mesylate group enhances water solubility. Moreover, the incorporation of peripheral 2-methoxyethoxy groups at the α-position modulates the electronic properties by altering the π-electron delocalization and enhancing photoacoustic signal amplitude. In addition, all the dyes were synthesized to incorporate an N-hydroxysuccinimidyl group to enable further bioconjugation. In summary, we report the synthesis of water-soluble silicon-centered naphthalocyanine dyes with a high photoacoustic signal amplitude that can potentially be used as contrast agents for molecular photoacoustic imaging.

An Approach to Minimize Tumour Proliferation by Reducing the Formation of Components for Cell Membrane

Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated β-cyclodextrin Sodium Salt (SBE-β-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 μM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.

A New Crystalline Ketoprofen Sodium Salt: Solid-State Characterization, Solubility, and Stability

Ketoprofen (KTP) is an Active Pharmaceutical Ingredient (API) that has low solubility in aqueous solvents. The use of KTP salts has attracted attention due to its improvements in terms of solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a crystalline KTP sodium salt (coded as KTP-Na) was successfully obtained and widely characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), solubility and accelerated stability studies. XRD results showed that KTP-Na is not yet reported in the literature. Moreover, FTIR, DSC and TGA were useful for differentiation of KTP-Na from the KTP commercialized form (coded as KTP-R1). The solubility of KTP-Na in water was about 80 times greater than the KTP-R1. However, KTP-Na showed lower physical stability in storage conditions at 40 ± 2°C/ 75% ± 5% RH when compared to KTP-R1, which was shown to be related to a high hygroscopicity of KTP-Na. Therefore, due to its higher solubility, KTP-Na may be a viable alternative for use in solid dosage forms. However, the presence of moisture must be strictly controlled to avoid water absorption and consequent amorphization.

Inclusion Complex of Gedunin-2-Hydroxypropyl-Β-Cyclodextrin Prepared by Kneading and Freeze-Drying Methods: Synthesis and Structural Characterization

Abstract The potential application of gedunin, a pharmacologically active limonoid, is limited in medicine because it has poor aqueous solubility. This study was aimed at preparation and characterization of an inclusion complex of gedunin and 2-hydroxypropyl-β-cyclodextrin (HBD) to increase the solubility in aqueous solvents and thus enhance the possibility of pharmaceutical formulation and oral administration of gedunin. Inclusion complex of gedunin isolated from Entandrophragma angolense heartwood with 2-hydroxypropyl-β-cyclodextrin (HBD) was prepared using freeze-drying and kneading methods. The gedunin-2-hydroxypropyl-β-cyclodextrin complex (GCD) was characterized using elemental analysis, Fourier-transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance (1H-NMR) and X-ray diffraction analysis (XRD). Elemental analysis indicated that gedunin and HBD formed 1:1 stoichiometric inclusion complex. Results of FT-IR indicated that gedunin was stabilized in HBD cavity by intra-molecular hydrogen bonds and van der Waals forces. 1H-NMR revealed that the entire gedunin molecule was not trapped into the core of the HBD. Nevertheless, the fraction trapped may be sufficient to enhance the apparent solubility of gedunin. XRD results showed the formation of new solid crystalline phase. The results obtained by different characterization techniques clearly indicated that both kneading and freeze-drying methods led to inclusion complex formation which may enhance oral administration of gedunin.

Study of dissolution and transfer processes of new bioactive thiazolo[4,5-d]pyrimidine derivatives in modeling biological systems

New thiazolo[4,5-d]pyrimidine derivatives were synthesized as potential antifungal agents. The amorphous nature of the obtained compounds was verified by DSC and PXRD. The kinetic and equilibrium solubilities of the derivatives were studied by the shake-flask method in pharmaceutically relevant solvents: buffer pH 2.0, buffer pH 7.4 and 1-octanol. It has been found that within the temperature range of (293.15–313.15) K the solubility of the compounds does not exceed 5 10-4 mol·L-1 in aqueous solvents and 6 10-2 mol·L-1 in alcohol. The solubility values were correlated by van’t Hoff and modified Apelblat equations. Based on the partition coefficients in the system 1-octanol/ buffer pH 7.4 the lipophilicity of the compounds have been estimated. The thermodynamic functions of dissolution and partition for the compounds studied in the solvents selected were calculated. It has been established that the transfer process of compounds from the aqueous phase to the organic is endothermic and entropy-controlled. The efficiency of the some computer’s programs to predict partition coefficients has been tested using experimental data. It was shown that the in vitro antifungal activity of the studied compounds increases with growth solubility in aqueous solvents.

Investigation of CO2 Solubility in Blends of AMP and HMDA Solvents: Thermodynamic Modeling Based on the Deshmukh-Mather Model

Among the various methods for CO2 removal from the atmosphere, CO2 absorption is considered as the most applicable one. Although several studies have been performed on CO2 absorption by using chemical solvents, there are not many studies on using improved absorbents. Therefore, the aim of this study was to measure the solubility of CO2 in utilized aqueous blends of 2-amino-2-methyl-1-propanol (AMP) and hexamethylenediamine (HMDA). In the present research, the equilibrium set up for measuring CO2 solubility in aqueous solvents was assembled. CO2 solubility experiments were carried out over a various range of CO2 partial pressures (8.44, 25.33, and 42.22 kPa) temperatures (303, 313, and 323 K) and solvent concentration (0.4, 1.8, 2, and 3 M). The results showed that increasing CO2 partial pressure or decreasing the temperature would lead to an increase in CO2 loading. Furthermore, with increasing HMDA concentration, CO2 loading reached a maximum value before it followed a slight decrease. The experimental results were fitted to the thermodynamic Deshmukh Mather model and the required parameters in this model were generated. The results showed that there is a good agreement between theoretical and experimental results of CO2 loading.

Ocular Delivery of Polyphenols: Meeting the Unmet Needs.

Nature has become one of the main sources of exploration for researchers that search for new potential molecules to be used in therapy. Polyphenols are emerging as a class of compounds that have attracted the attention of pharmaceutical and biomedical scientists. Thanks to their structural peculiarities, polyphenolic compounds are characterized as good scavengers of free radical species. This, among other medicinal effects, permits them to interfere with different molecular pathways that are involved in the inflammatory process. Unfortunately, many compounds of this class possess low solubility in aqueous solvents and low stability. Ocular pathologies are spread worldwide. It is estimated that every individual at least once in their lifetime experiences some kind of eye disorder. Oxidative stress or inflammatory processes are the basic etiological mechanisms of many ocular pathologies. A variety of polyphenolic compounds have been proved to be efficient in suppressing some of the indicators of these pathologies in in vitro and in vivo models. Further application of polyphenolic compounds in ocular therapy lacks an adequate formulation approach. Therefore, more emphasis should be put in advanced delivery strategies that will overcome the limits of the delivery site as well as the ones related to the polyphenols in use. This review analyzes different drug delivery strategies that are employed for the formulation of polyphenolic compounds when used to treat ocular pathologies related to oxidative stress and inflammation.

Energy transfer mechanisms in pH-tuned aggregates of curcumin.

Curcumin ((1,7-bis-(4-hidroxi-3-metoxifenil)-1,6-heptadieno-3,5-diona)), is a natural yellow-orange polyphenol dye, obtained from Curcuma longa rhizomes, with vast potential in the biotechnology field, such as anti - inflammatory and cancer preventive properties, and a very environmental-sensible structure, mostly resulting in aggregate formations, with low solubility in aqueous solvents and remarkable pH dependence. Hence, it is essential to comprehend its aggregation mechanisms, optical properties and conformational equilibrium to develop curcumin-based drugs and biomaterials for several applications. With the purpose of understand such concepts and its properties, the results presented in this work, obtained through spectroscopic measurements and the Hill's modeling, show a conformational equilibrium, driven by pH, between the enol-enolate and aggregated forms in curcumin, and the respective energy transfer processes between these species. Additionally, the photophysical mechanisms for the energy transfer between aggregated forms, observed with the ellipsometry measurements, showed an "all-or-nothing" character, pointing to a very complex conformation for curcumin aggregates.

In-Situ Gelling Liquid Crystal Mucoadhesive Vehicle for Curcumin Buccal Administration and Its Potential Application in the Treatment of Oral Candidiasis.

The treatments of oral candidiasis involve azole-based antifungals; however, the fungal resistance of these drug compounds has been detected in worldwide. Therefore, the discovery of new molecules from natural sources, such as curcumin, has been reported for the treatment of fungal diseases. However, this drug has poor solubility in aqueous solvents and presents low bioavailability. Thus, the system was designed for a low viscosity precursor of a liquid crystal phase, and saliva leads a phase behaviour increasing the viscosity of system and the residence time in the mucosa and promotes antifungal activity Formulation composed of PPG-5-CETETH-20, oleic acid and water (30, 30, 40% w/w) denominated F. This formulation was diluted with artificial saliva at 10, 20 and 30% (w/v). These formulations were characterized by polarized light microscopy (PLM), mechanical behaviour, oscillatory rheology and performance studies on mucosa. In vitro studies were performed against a standard strain (ATTC 18804) or buccal isolated clinical strains for determinate the minimum inhibitory concentrations (MIC). PLM and Small-Angle X-ray Scattering (SAXS) revealed that formulation F is lamellar mesophase, whereas its dilution with artificial saliva changed the system to anisotropic hexagonal mesophase. Textural profiles show the increasing with the dilution of precursor system. Rheological measurements show that diluted systems exhibit elastic modulus values (G') than viscous modulus (G'') and it indicates more micro-structured system. Mucoadhesive force against excised porcine oesophageal mucosa showed that systems have properties mucoadhesive. Ex vivo retention studies on porcine oesophageal mucosa exhibited an increase of 5-fold and 3-fold in the retention of curcumin from F and F30, respectively. In vitro antifungal assay against Candida albicans revealed that curcumin-loaded systems were more potent against a standard strain (ATTC 18804) and buccal isolated strains compared with a curcumin solution. Hence, the physicochemical characterization, combined with ex vivo and in vitro studies, revealed that formulation designed could form a in situ gelling mucoadhesive with buccal retention of curcumin and the increase of its antifungal activity with great potential in the treatment of oral candidiasis.

Cationic dipyridylamine substituted zinc tetrapyrazinoporphyrazine derivatives for photodynamic therapy

Two kinds of cationic zinc tetrapyrazinoporphyrazine derivatives substituted with ortho- or para- methylpyridinium groups on the peripheral position were synthesized and characterized. The solubility and aggregation behavior of each material were estimated in various solvents, which show different aspect depending on the position of nitrogen on methylpyridinium groups. The fluorescence quantum yield (ΦF) values of both cationic tetrapyrazinoporphyrazines were measured and the singlet oxygen quantum (ΦΔ) yield value were measured by indirect method with DPBF (1,3-diphenylisobenzofuran) in DMSO. Both ΦF and ΦΔ of cationic zinc tetrapyrazinoporphyrazine derivatives exhibited reasonable values for photodynamic therapy application. The cationic zinc tetrapyrazinoporphyrazine derivatives substituted methylpyridinium groups increased solubility in aqueous solvent but also showed the suitable properties as the photosensitizers for photodynamic therapy.

Antiplasmodial dihetarylthioethers target the coenzyme A synthesis pathway in Plasmodium falciparum erythrocytic stages

BackgroundMalaria is a widespread infectious disease that threatens a large proportion of the population in tropical and subtropical areas. Given the emerging resistance against the current standard anti-malaria chemotherapeutics, the development of alternative drugs is urgently needed. New anti-malarials representing chemotypes unrelated to currently used drugs have an increased potential for displaying novel mechanisms of action and thus exhibit low risk of cross-resistance against established drugs.ResultsPhenotypic screening of a small library (32 kinase-inhibitor analogs) against Plasmodium falciparum NF54-luc asexual erythrocytic stage parasites identified a diarylthioether structurally unrelated to registered drugs. Hit expansion led to a series in which the most potent congener displayed nanomolar antiparasitic activity (IC50 = 39 nM, 3D7 strain). Structure–activity relationship analysis revealed a thieno[2,3-d]pyrimidine on one side of the thioether linkage as a prerequisite for antiplasmodial activity. Within the series, the oxazole derivative KuWei173 showed high potency (IC50 = 75 nM; 3D7 strain), good solubility in aqueous solvents (1.33 mM), and >100-fold selectivity toward human cell lines. Rescue experiments identified inhibition of the plasmodial coenzyme A synthesis as a possible mode of action for this compound class.ConclusionsThe class of antiplasmodial bishetarylthioethers reported here has been shown to interfere with plasmodial coenzyme A synthesis, a mechanism of action not yet exploited for registered anti-malarial drugs. The oxazole congener KuWei173 displays double-digit nanomolar antiplasmodial activity, selectivity against human cell lines, high drug likeness, and thus represents a promising chemical starting point for further drug development.

Surface Coating Effect on Structural, Optical and Photoluminescence Properties of Eu3+ Doped Yttrium Fluoride Nanoparticles

Europium doped yttrium fluoride (YF3:Eu) nanoparticles(core-NPs) with and without a passive layer of LaF3 coating around the core-NPs were prepared by simple polyol process. The surface of these luminescent core/shell-NPs was additionally functionalized with amorphous silica. The phase purity, crystalinity, shapes and size of the as-prepared core and their respective core/shell-NPs were determined by X-ray diffraction (XRD) pattern and transmission electron microscopy (TEM). The as-prepared core/shell-NPs were successfully grafted with silica layer as verified by Fourier transform infrared spectroscopy (FTIR). As observed from absorption spectra, the energy band gap was decreased after core/shell formation because of increase in grain size of the luminescent-NPs. The core/shell-nanostructure synthesized by this method exhibited a remarkable enhancement than their respective core-NPs. However, the emission intensity was suppressed after silica surface coating because of non-radiative transitions effect. The presence of silanol (Si–OH) groups on their surfaces not only results in high solubility in aqueous solvents, but also allows further conjugation with biomolecules such as antigens, antibodies and oligonucleotides, which pave the way for potential bio-applications of the core/shell/SiO2-NPs.

Impact of surface coating on morphological, optical and photoluminescence properties of YF3:Tb3+ nanoparticles

A simple polyol and sol–gel Stober process were employed for synthesis of YF3:Tb+ (core), YF3:Tb+@LaF3 (core/shell) and YF3:Tb+@LaF3@SiO2 (core/shell/SiO2) nanoparticles (NPs). The phase purity, crystalinity, morphology, optical and photoluminescence properties were investigated and discussed with the help of various analytical techniques including X-ray diffraction pattern, FE-transmission electron microscopy (TEM), FTIR, UV/vis absorption, energy band gap and emission spectra. XRD and FE-TEM studies indicate the formation of core/shell nanostructure and ∼10nm thick amorphous silica surface coating surrounding the core-NPs, which is also confirmed by FTIR spectral results. The surface modifications of core-NPs significantly affect the optical features in the form of energy band gap, which were correlated with particle size of the nanomaterials. The comparative emission spectral results show that after inert layer coating the luminescent core-NPs display stronger emission intensity in respect to core and silica coated core/shell/SiO2-NPs. The solubility character along with colloidal stability was improved after silica surface modification, whereas luminescent intensity was suppressed causing the surface functionalized with high energy silanol (Si-OH) molecules. These novel luminescent nanomaterials with enhanced emission intensity and excellent solubility in aqueous solvents would be potentially useful for fluorescence bioimaging/optical bio-probe etc.

Enhanced Neuroprotection of Acetyl-11-Keto-β-Boswellic Acid (AKBA)-Loaded O-Carboxymethyl Chitosan Nanoparticles Through Antioxidant and Anti-Inflammatory Pathways.

Acetyl-11-keto-β-boswellic acid (AKBA), a main active constituent from Boswellia serrata resin, is a novel candidate for therapy of cerebral ischemia-reperfusion (I/R) injury. Nevertheless, its poor solubility in aqueous solvent, bioavailability, and rapid clearance limit its curative efficacy. To enhance its potency, in our study, AKBA-loaded o-carboxymethyl chitosan nanoparticle (AKBA-NP) delivery system was synthesized. The transmission electron microscopy and transmission electron microscope images of AKBA-NPs suggested that particle size was 132 ± 18nm, and particles were spherical in shape with smooth morphology. In pharmacokinetics study, AKBA-NPs apparently increases the area under the curve of plasma concentration-time and prolonged half-life compared with AKBA. The tissue distribution study confirmed that AKBA-NPs had a better brain delivery efficacy in comparison with AKBA. The results from our pharmacodynamic studies showed that AKBA-NPs possess better neuroprotection compared with AKBA in primary neurons with oxygen-glucose deprivation (OGD) model and in animals with middle cerebral artery occlusion (MCAO) model. Additionally, AKBA-NPs modulate antioxidant and anti-inflammatory pathways more effectively than AKBA by increasing nuclear erythroid 2-related factor 2 and heme oxygenase-1 expression, and by decreasing nuclear factor-kappa B and 5-lipoxygenase expression. Collectively, our results suggest that AKBA-NPs serve as a potent delivery vehicle for AKBA in cerebral ischemic therapy.

A curcumin-loaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis.

Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis.

HPLC analysis and extraction method of SN-38 in brain tumor model after injected by polymeric drug delivery system.

SN-38 is a highly potent anticancer drug but its poor solubility in aqueous solvent and adverse side effects limit clinical applications. To overcome these limitations, SN-38-loaded-injectable drug delivery depots have been intratumorally administered in xenograft tumor model in nude mice. The extraction and high performance liquid chromatography (HPLC) were performed in order to determine the amount of SN-38 inside tumors. SN-38 was extracted from tumors using DMSO. HPLC analysis was validated and resulted in linearity over the concentration range from 0.03 to 150 µg/mL (r(2) ≥ 0.998). Lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were 0.308 µg/mL and 1.02 µg/mL, respectively. The extraction efficiency (% recovery) of SN-38 in porcine tissues was similar to that of tumors which provided more than 90% recovery in all concentrations. Moreover, the variability of precision and accuracy within and between-day were less than 15%. Therefore, this extraction and HPLC protocol was applied to determine the amount of SN-38 in tumors. Results show higher remaining amount of SN-38 in tumor from SN-38-loaded polymeric depots than that of SN-38 solution. These results reveal that SN-38-loaded polymeric depots can prevent the leakage of free-drug out of tumors and can sustain higher level of SN-38 inside tumor. Thus, the therapeutic efficacy can be elevated by SN-38-loaded polymeric depots.

Superior sensing performance of multi-walled carbon nanotube-based electrodes to detect unconjugated bilirubin

The direct electrochemical behaviour of bilirubin in the physio-pathological concentration range and at physiological pH was investigated by cyclic voltammetry. Nanostructured electrodes with a thin film of multi-walled carbon nanotubes exhibited a higher sensing performance than bare electrodes. The detection limit obtained with nanostructured electrodes (4.2±0.1μM) allows the detection of both normal and pathological levels of bilirubin. Due to its sparse solubility in aqueous solvents, in human fluids bilirubin is found in the form of soluble complex with albumin. Therefore, the nanostructured-sensor response was studied in presence of different concentrations of this protein. A signal weakening was observed with increasing concentrations of albumin due to the decrease of free bilirubin. Finally, bilirubin detection was tested at concentrations typical of newborn jaundice (200–500μM) and in the presence of normal albumin levels. A detection limit of 9.4±0.3μM was identified. Since this value is below the minimum critical bilirubin concentration for newborns, our sensor, modified with a thin film of carbon nanotubes, could potentially be used for bilirubin detection in cases of newborn jaundice.

Chemoprevention of azoxymethane-initiated colon cancer in rat by using a novel polymeric nanocarrier–curcumin

Curcumin is a potential natural anticancer drug with limited bioavailability due to the lack of solubility in aqueous solvents. The present study is designed to investigate the preventive effects of polymeric nanocarrier–curcumin (PNCC) on colon carcinogenesis in an azoxymethane-induced rat tumor. Forty rats were divided into control, curcumin- and PNCC-treated groups. Animals received azoxymethane (AOM) as a carcinogenic agent (15mg/kg, s.c.) weekly for two consecutive weeks. They were given curcumin 0.2% and PNCC two weeks before till 14 weeks after the last injection of AOM. In the end, post euthanasia, the entire gastrointestinal tract was scrutinized for tumors, and the rest of the body for metastatic deposits. Tumor number, size and location were characterized. The histopathological and immunohistochemistry examinations were also performed on colon tissue. In vivo, curcumin nanoparticles inhibited colon cancer growth in animal model. The tumors incidence and number decreased by nanocurcumin comparison with control. Furthermore, the nuclear/cytoplasmic ratio, epithelial stratification, nuclear dispolarity, goblet depletion, structural abnormality, and the expression of Beta-catenin and Bcl-2 proteins were reduced in PNCC compared to others groups (P<0.05). In addition, Bax protein expression was significantly increased in PNCC in comparison with control and curcumin-treated groups (P<0.001). The present study demonstrated the potential anticancer effects of PNCC in a typical animal model. The results provide evidence that nanopolymeric curcumin exerts a significant chemopreventive effect on AOM-initiated colon cancer through cell proliferation inhibition and apoptosis induction. More investigations are needed to confirm its safety for human use.

Profiling of integral membrane proteins and their post translational modifications using high-resolution mass spectrometry

Integral membrane proteins pose challenges to traditional proteomics approaches due to unique physicochemical properties including hydrophobic transmembrane domains that limit solubility in aqueous solvents. A well resolved intact protein molecular mass profile defines a protein’s native covalent state including post-translational modifications, and is thus a vital measurement toward full structure determination. Both soluble loop regions and transmembrane regions potentially contain post-translational modifications that must be characterized if the covalent primary structure of a membrane protein is to be defined. This goal has been achieved using electrospray-ionization mass spectrometry (ESI-MS) with low-resolution mass analyzers for intact protein profiling, and high-resolution instruments for top-down experiments, toward complete covalent primary structure information. In top-down, the intact protein profile is supplemented by gas-phase fragmentation of the intact protein, including its transmembrane regions, using collisionally activated and/or electron-capture dissociation (CAD/ECD) to yield sequence-dependent high-resolution MS information. Dedicated liquid chromatography systems with aqueous/organic solvent mixtures were developed allowing us to demonstrate that polytopic integral membrane proteins are amenable to ESI-MS analysis, including top-down measurements. Covalent post-translational modifications are localized regardless of their position in transmembrane domains. Top-down measurements provide a more detail oriented high-resolution description of post-transcriptional and post-translational diversity for enhanced understanding beyond genomic translation.

RETRACTED: Cyclodextrin-complexed curcumin exhibits anti-inflammatory and antiproliferative activities superior to those of curcumin through higher cellular uptake

Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with multiple beneficial activities, but its optimum potential is limited by poor bioavailability, in part due to the lack of solubility in aqueous solvents. To overcome the solubility problem, we have recently developed a novel cyclodextrin complex of curcumin (CDC) and examined here this compound for anti-inflammatory and antiproliferative effects. Using the electrophoretic mobility shift assay, we found that CDC was more active than free curcumin in inhibiting TNF-induced activation of the inflammatory transcription factor NF-kappaB and in suppressing gene products regulated by NF-kappaB, including those involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). CDC was also more active than free curcumin in inducing the death receptors DR4 and DR5. Annexin V staining, cleavage of caspase-3 and PARP, and DNA fragmentation showed that CDC was more potent than free curcumin in inducing apoptosis of leukemic cells. Antiproliferative assays also demonstrated that CDC was more active than free curcumin in suppressing proliferation of various cancer cell lines. The cyclodextrin vehicle had no effect in these assays. Compared with free curcumin, CDC had a greater cellular uptake and longer half-life in the cells. Overall we demonstrated that CDC had superior attributes compared with free curcumin for cellular uptake and for antiproliferative and anti-inflammatory activities.