A novel bioavailable curcumin-galactomannan complex modulates the genes responsible for the development of chronic diseases in mice: A RNA sequence analysis.

BACKGROUND: Chronic diseases or non-communicable diseases are a major burden worldwide due to the lack of highly efficacious treatment modalities and the serious side effects associated with the available therapies. PURPOSE/STUDY DESIGN: A novel self-emulsifying formulation of curcumin with fenugreek galactomannan hydrogel scaffold as a water-dispersible non-covalent curcumin-galactomannan molecular complex (curcumagalactomannosides, CGM) has shown better bioavailability than curcumin and can be used for the prevention and treatment of chronic diseases. However, the exact potential of this formulation has not been studied, which would pave the way for its use for the prevention and treatment of multiple chronic diseases. METHODS: The whole transcriptome analysis (RNAseq) was used to identify differentially expressed genes (DEGs) in the liver tissues of mice treated with LPS to investigate the potential of CGM on the prevention and treatment of chronic diseases. Expression analysis using DESeq2 package, GO, and pathway analysis of the differentially expressed transcripts was performed using UniProtKB and KEGG-KAAS server. RESULTS: The results showed that 559 genes differentially expressed between the liver tissue of control mice and CGM treated mice (100 mg/kg b.wt. for 14 days), with adjusted p-value below 0.05, of which 318 genes were significantly upregulated and 241 were downregulated. Further analysis showed that 33 genes which were upregulated (log2FC > 8) in the disease conditions were significantly downregulated, and 32 genes which were downregulated (log2FC < -8) in the disease conditions were significantly upregulated after the treatment with CGM. CONCLUSION: Overall, our study showed CGM has high potential in the prevention and treatment of multiple chronic diseases.

Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant. Two gas generating agent (s) incorporated were sodium bicarbonate and citric acid. All compendial pre and post-compression tests results were in the acceptable limits. FTIR analysis confirmed drug-polymer compatibility. The in-vitro drug release in simulated conditions i.e., 0.1 N HCl for 12 h revealed orderly increase in total floating time, i.e., less than 6 h for F1 over 12 h for F9. Formulations F1 to F4 were not capable to retard drug release up to 12 h, whereas F5-F7 for 12 h, while F8 and F9 for more than 12 h. Data fitting in various kinetic models showed that drug release best fit in first order kinetic model and F9 in zero order. Based on results data, F7 was the best among all.

Research progress in galactomannan-based nanomaterials: Synthesis and application.

Galactomannans are naturally occurring biocompatible and biodegradable nonionic polysaccharides comprised of mannose and galactose residues. They are under investigation for the design of various drug delivery carriers such as matrix tablets, microparticles, nanoparticles/nanocomposites, polymeric micelles, hydrogels, as well as pharmaceutical excipients. Amongst galactomannans, guar gum, locust bean gum, and fenugreek gum are the biomaterials mostly investigated for their potential utility as nanocarriers for various purposes, either in their native or modified forms. The galactomannan-based nanomaterials have been fabricated by adopting various strategies. These galactomannan nanomaterials have been tested for oral vaccination, oral insulin delivery, cancer cell & macrophage targeting, controlled drug delivery, heavy metal extraction and wound dressing applications. The galactomannan has attracted the attention of researchers as reducing agents for the green synthesis of metal nanoparticles as well. These nanometals have shown improved antimicrobial, antioxidant and anticancer activities. In vitro toxicity of the nanomaterials is also assessed in some instances. Others such as cassia gum, tara gum, Delonix, Leucaena leucocephala, Punica granatum galactomannans are amongst the least studied materials for biological applications. This review describes various strategies adopted for the synthesis of galactomannan-based nanomaterials, their properties and applications, especially in the field of drug delivery.

Influence of the reducing-end anomeric configuration of the Man9 epitope on DC-SIGN recognition.

High-mannose (Man9GlcNAc2) is the main carbohydrate unit present in viral envelope glycoproteins such as gp120 of HIV and the GP1 of Ebola virus. This oligosaccharide comprises the Man9 epitope conjugated to two terminal N-acetylglucosamines by otherwise rarely-encountered ß-mannose glycosidic bond. Formation of this challenging linkage is the bottleneck of the few synthetic approaches described to prepare high mannose. Herein, we report the synthesis of the Man9 epitope with both alpha and beta configurations at the reducing end, and subsequent evaluation of the impact of this configuration on binding to natural receptor of high-mannose, DC-SIGN. Using fluorescence polarization assays, we demonstrate that both anomers bind to DC-SIGN with comparable affinity. These relevant results therefore indicate that the more synthetically-accesible Man9 alpha epitope may be deployed as ligand for DC-SIGN in both in vitro and in vivo biological assays.

Synthesis of quaternised guar gum using Taguchi L(16) orthogonal array.

Quaternised polysaccharides have diverse applications due to introduction of quaternary ammonium groups in the biopolymer. In the present study, quaternization of guar gum was carried out by adopting the Taguchi's approach of robust design of experiments for optimizing the levels of the factors to obtain quaternized guar gum with higher DS. The methodology employed far less number of experiments than the classical method which necessitates higher number of chemical reactions to achieve the required derivatisation. The application of Taguchi's L16 (45) orthogonal array resulted in DS of 0.49. The optimized experimental levels were 3.24 mol/AGU of NaOH and 2.04 mol/AGU of CHPTAC for 2 h at 30 °C keeping the gum: liquor ratio 1:20. The study established that Taguchi methodology provided a statistically sound and green approach for optimization of reaction conditions. The modified products were characterised by FTIR, 1H-NMR, 13C-NMR, DEPT-135, HSQC and HMBC spectroscopic methods.

Guar gum cinnamate ouzo nanoparticles for bacterial contact killing in water environment.

Herein we report the synthesis of newer guar gum cinnamate esters (GGC) following a Hofmeister cation guided homogeneous phase reaction. High degree of substitution (DS) guar gum cinnamate was obtained using, cinnamic acid halide reactant at a 1:3 M ratio. The biopolymer was fully characterized in FT-IR,13C NMR, XRD and thermal analysis. Nanoparticles were further developed in a facile ouzo solvent diffusion technique. SEM studies confirmed quasi spherical shape of the nanoparticles (GGCN) with an average size of 200 nm. Nanoparticles GGCN, expressed antibacterial activity against water borne gram negative and gram positive bacteria. The MIC was recorded at 300 µg mL-1against Escherichia coli and 500 µg mL-1against Staphylococcus aureus. Bacterial contact killing was confirmed from the bacterial morphology studies in SEM. Thus, nanoparticles from GGC may be employed for bacterial killing and water decontamination.

Konjac glucomannan/polyvinyl alcohol nanofibers with enhanced skin healing properties by improving fibrinogen adsorption.

Skin tissue engineering aims to develop the effective healing strategy to repair the wound by optimizing skin scaffold materials. During the skin wound healing process, fibrin plays an important role due to the specific blood coagulation effect. In this study, the outstanding fibrin capability of konjac glucomannan (KGM) is demonstrated by the molecular dynamics simulation and confirmed by the protein adsorption experiments. A series of konjac glucomannan/polyvinyl alcohol (KGM/PVA) composites with different ratio are fabricated and their role in enhancing the skin repair is tested by in vitro cell culture and in vivo study. The Eads (adsorption energy) between fibrin and KGM is about 30% larger than that between fibrin and PVA. The fibrinogen adsorption rates of PVA and KGM/PVA (5:5) composites can reach about 20% and 60%, respectively. The results show the blood adsorption capacity of KGM/PVA (5:5) composite can reach about 13 g/g. After 7 days of cell culture, the optical density values of 3T3 fibroblasts on KGM/PVA (5:5) composite could reach 0.8. The mechanical properties of the composites are also verified to meet the practical needs. Thus, we propose a potential wound dressing material strategy based on the materials design and the intrinsic properties of KGM.

Sonication-assisted synthesis of a new heterostructured schiff base ligand Silver-Guar gum encapsulated nanocomposite as a visible light photocatalyst.

A heterostructured Schiff base ligand (Benzildiethylenetriamine)-Silver-Guar gum encapsulated nanocomposites was intended to prepare by simple sonication assisted reflux method. Appropriate composition of purified guar gum, Schiff base ligand and silver nitrate were used for the synthesis. The synthesised nanocomposites were characterised by photoluminescence spectrum, UV-vis diffuse reflectance spectrophotometer, Fourier transform infra-red spectroscopy, X-ray diffractometer, scanning electron microscopy and transmission electron microscopy. The crystalline peaks of XRD and FTIR reveals that Schiff base ligand and guar gum forms metal-organic matrix. Morphology studies have confirmed the organic framework structure and metallic silver nanoparticles are embedded on the organic framework. The efficiency of nanocomposites depends on adsorption capacity and silver nanoparticles that are encapsulated thereby increasing the visible light absorption through surface plasma resonance. The nanocomposite was proved to be highly selective in hydrogenation reaction which favoured the formation of aniline from nitrobenzene as single product with short reaction time and 90% conversion.

Automated solution-phase syntheses of alpha 1 → 2, 1 → 3 type rhamnans and rhamnan sulfate fragments.

Rhamnan and rhamnan sulfate are naturally occurring carbohydrates that have important biological functions and possible therapeutic applications, but studies are limited to the microheterogeneous mixtures from natural sources. This work reports the first synthesis of any sulfated rhamnan fragments and successful automation of the process with a recently developed automated solution-phase approach using N-iodosuccinimide/trimethylsilyl triflate (NIS/TMSOTf) promotor and levulinoyl ester deprotection conditions. The automated solution-phase activation/deprotection approach was initially able to create alpha 1 → 2, 1 → 3 type rhamnan di- and trisaccharide in moderate yields. Once these targets were achieved, a process to use SO3•pyridine complex in DMF for sulfation compatible with an automated solution-phase liquid handling system was developed and successfully applied to carbohydrate sulfation to create two rhamnan sulfate fragments with differing monosulfation patterns.

Sonochemical synthesis of gum guar biopolymer stabilized copper oxide on exfoliated graphite: Application for enhanced electrochemical detection of H2O2 in milk and pharmaceutical samples.

A novel and cost-effective synthesis of biopolymer-based organic and inorganic composite materials have received substantial attention in a broad range application including electroanalysis of small molecules. In this perspective, we report the synthesis of gum guar (guar) biopolymer stabilized cupric oxide decorated on exfoliated graphite (GR-guar/CuO) composite. Different physicochemical characterization methods were used to confirm the successful exfoliation of graphite and formation of the GR-guar/CuO composite. A simple sonochemical method has been used for the preparation of guar stabilized exfoliated graphite (GR-guar). The flower-like CuO on GR-guar and guar stabilized CuO (CuO-guar) composites were synthesized using a hydrothermal method. Cyclic voltammetric studies revealed that the GR-guar/CuO composite modified screen-printed carbon electrode (SPCE) had enhanced electro-reduction ability towards H2O2 than GR-guar and pristine graphite/CuO-guar modified SPCEs. Under optimized experimental conditions, the GR-guar/CuO composite modified electrode detects H2O2 in the response ranges from 0.02 to 1296.6 µM. The sensor shows a lower detection limit of 5.8 nM with high sensitivity. The as-prepared GR-guar/CuO composite sensor is highly reproducible and had excellent selectivity and practicality towards the detection of H2O2. Consequently, the fabricated sensor can be used for the accurate detection of H2O2 in real samples.

Characterization and in vitro evaluation of chitosan/konjac glucomannan bilayer film as a wound dressing.

A novel bilayer film of chitosan and konjac glucomannan were prepared by the two-step casting technique. Blend films were also prepared to investigate the interactions between the two polymers in the interfacial region of the bilayer structure. Scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis showed that, unlike in the blends, the physicochemical properties of each biopolymer were preserved in the bilayer film. Differential scanning calorimetry and thermogravimetric analysis also indicated a good thermostability and miscibility for both polymers, probably due to strong hydrogen bonds between their polymer chains. Biological, mechanical and water vapor transmission tests showed a high biocompatibility, low cytotoxicity, and suitable mechanical and barrier properties of the bilayer films for wound dressing applications.

Stability of cationic and amphoteric derivatives of mannan from the yeast Candida albicans.

Infection with Candida albicans can prove lethal in immuno-compromised patients. It is imperative to develop a vaccine against this common organism. The amphoteric derivatives of the mannan component of the Candida cell wall may present a prospective target for the development of such a vaccine; however, the radical processing by antigen-presenting cells of the immune system is not fully understood. In this work a set of tailor-made cationic and amphoteric derivatives of three different degrees of quaternization (DSQ 0.14-0.38) has been prepared by chemical modification of ultrasonically-treated mannan and three carboxymethylated mannan derivatives (DSCM 0.13-0.32). These were exposed to free-radical attack by OH, generated in situ by the Fenton reaction. Potential changes in composition, DSQ, and molar mass distribution due to free-radical degradation were monitored by elemental analysis, NMR and FTIR spectroscopies, and size exclusion chromatography. A protective effect of quaternization against OH degradation was found. Non-isothermal thermogravimetric analysis found that the thermal stability of this mannan was also improved by chemical modification.

Synthesis and characterization of biopolymer based hybrid hydrogel nanocomposite and study of their electrochemical efficacy.

A highly competent material, based on poly lactic acid (PLLA) grafted hydroxypropyl guar gum (HPG-g-PLLA) and polypyrrole/carboxylated multiwalled carbon nanotube (PPy/C-MWCNT) composite of various binary composition and copolymer of one of these nanocomposites have been synthesized successfully by in-situ polymerization. The environmentally affable nanocomposites have been characterized by spectroscopy, microscopy and thermogravimetry. Cytotoxicity of bio-nanocomposite has been inquired by cell viability study, which reveals its eco-friendly nature. The electrochemical properties of the biomaterials have been appraised by cyclic voltammetric studies. The PPy/C-MWCNT composite having 1 wt% C-MWCNT appears as the optimum composition from electrochemical studies. The hydrogel nanocomposite (HPG-g-PLLA5/0.5) copolymer behaves as a super ordinate material than pure PPy and PPy/C-MWCNT in every aspect of electrochemical properties like current density, stability, processibility and reversibility. Moreover the hydrogel nanocomposite, making electrode fabrication more simple and binder-free, nullifies all the interfacial complications arising from binders as well.

In Vitro Synthesis and Crystallization of ß-1,4-Mannan.

In vitro polymerization of ß-mannans is a challenging reaction due to the steric hindrance confered by the configuration of mannosyl residues and the thermodynamic instability of the ß-anomer. Whatever the approach used to date-whether chemical, or enzymatic with glycosynthases and mannosyltransferases-pure ß-1,4-mannans have never been synthesized in vitro. This has limited attempts to investigate their role in the production of plant and algal cell walls, in which they are highly abundant. It has also impeded the exploitation of their properties as biosourced materials. In this paper, we demonstrate that TM1225, a thermoactive glycoside phosphorylase from the hyperthermophile species Thermotoga maritima, is a powerful biocatalytic tool for the ecofriendly synthesis of pure ß-1,4-mannan. The recombinant production of this enzyme and its biochemical characterization allowed us to prove that it catalyzes the reversible phosphorolysis of ß-1,4-mannosides, and determine its role in the metabolism of the algal mannans on which T. maritima feeds in submarine sediments. Furthermore, after optimizing the reaction conditions, we exploited the synthetic ability of TM1225 to produce ß-1,4-mannan in vitro. At 60 °C and from d-mannose 1-phosphate and mannohexaose, the enzyme synthesized mannoside chains with a degree of polymerization up to 16, which precipitated into lamellar single crystals. The X-ray powder diffraction and base-plane electron diffraction patterns of the lamellar crystals unambiguously show that the synthesized product belongs to the mannan I family previously observed in planta in pure linear mannans, such as those of the ivory nut. The in vitro formation of these mannan I crystals is likely determined by the high reaction temperature and the narrow chain length distribution of the insoluble chains.

The synthesis of a new macromolecule for the sentinel node detection: 99mTc-gly-mannosyl-dextran.

OBJECTIVE: We aimed to design and synthesize a new macromolecule for sentinel node detection to improve the imaging quality and avoid possible adverse effect. BACKGROUND: The imaging of sentinel lymph node has been an important field in the nuclear medicine. A lot of imaging agents have been developed, including Tc-sulfer colloid, Tc-labeled dextrans and the latest Tc-DTPA-mannosyl-dextran. With the technology advanced, the imaging ability of the agents has been better and better. However, there are still some drawbacks. MATERIALS AND METHODS: The new macromolecule agent was based on the dextran macromolecule backbone. Then the gly-gly-gly and mannose molecules were conjugated onto the backbone proportionally by targeting two different reaction sites. Once the new macromolecule was labelled with Tc, its imaging ability was tested by single-photon emission computed tomography scanning with Tc-sulfur colloid as the comparison. RESULTS: The average numbers of gly-gyl-gyl and mannosyl groups on the dextran backbone are determined to be ∼1: 2 per dextran. The average molecular diameter and molecular weight are measured to be 5.4±0.7 nm and 10 324 g/mol, respectively. The macromolecule is labelled by Tc with 93.2±2.4% radiochemical yield. The lymphatic imaging by single-photon emission computed tomography with the labeled compound showed no worse imaging ability but cost less time than the commercially available Tc-sulfur colloid. CONCLUSION: A new macromolecule imaging agent for sentinel node detection has been synthesized with better imaging ability and less imaging time cost.

Synthesis and structure characterization of sulfated galactomannan from fenugreek gum.

Sulfated derivatives of the galactomannan family have multiple biological activities. In the present study, sulfated galactomannan from fenugreek gum (SFG) were prepared by chlorosulfuric acid/pyridine (CSA/Py) method. In order to acquire the derivatives with the highest degree of substitution (DS), the experiment optimum conditions of the sulfation were determined by Box-Behnken design (BBD). The quadratic regression model analysis confirmed that reaction time was the most significant parameter for the impact of DS. Under the selected conditions, maximum DS was obtained as 0.490. Results of FT-IR and X-ray photoelectron spectroscopy (XPS) indicated the present of SO3- group. In 13C NMR spectroscopy, the original C-6 peaks did not disappear completely and the newly peaks appeared at δ 63.2 and 64.0 illustrating the incomplete substitution were predominantly on C-6 position. After sulfation, size exclusion chromatography combined with multi-angle laser light scattering (SEC-MALLS) detected all the weight average molecular mass (MW) of sulfated derivatives decrease rapidly. The introduction of the electrostatic interaction of negatively charged SO3- groups and the decrease in MW could have a significant effect on its biological activity.

Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery.

Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.

Synthetic polymannose as a drug carrier: synthesis, toxicity and anti-fungal activity of polymannose-amphotericin B conjugates.

Polymannose (PM) having a weight-average molar mass (Mw) of 30-53 kDa was synthesized by the polycondensation of mannose using phosphorous acid as the catalyst and characterized by various techniques such as NMR, IR, GPC and polarimetry. 2D NMR results confirmed the presence of (1 â†’ 6)-linked α-D-mannose residues as backbone with O-3 and O-2 substituted linear or branched chains in PM. Amphotericin B (AmB) was conjugated to periodate-oxidized PM through Schiff's linkages at 20 wt% concentration. The AmB-PM conjugates were highly soluble in phosphate buffered saline (180-250 mg/mL), exhibited negligible hemolytic potential to human erythrocytes even at a concentration of 200 µg/mL (equivalent to ~40 µg/mL AmB) and were non-toxic to human embryonic kidney (HEK293T) cells even at a concentration of 250 µg/mL (equivalent to ~50 µg/mL AmB). The minimum inhibitory concentration of the AmB-PM conjugates against C. albicans, C. parapsilosis and C. neoformans was in the range of 0.5-1.0 µg/mL. Mannose receptors are widely expressed on myeloid cells such as macrophages, neutrophils, and dendritic cells. Therefore, apart from treating fungal infections, AmB-PM conjugates also may have therapeutic potential for the treatment of macrophage-associated diseases such as leishmaniasis where mannose receptors are overexpressed.

Novel mouse monoclonal antibodies specifically recognize Aspergillus fumigatus galactomannan.

A panel of specific monoclonal antibodies (mAbs) against synthetic pentasaccharide ß-D-Galf-(1→5)-[ß-D-Galf-(1→5)]3-α-D-Manp, structurally related to Aspergillus fumigatus galactomannan, was generated using mice immunized with synthetic pentasaccharide-BSA conjugate and by hybridoma technology. Two selected mAbs, 7B8 and 8G4, could bind with the initial pentasaccharide with affinity constants of approximately 5.3 nM and 6.4 nM, respectively, based on surface plasmon resonance-based biosensor assay. The glycoarray, built from a series of synthetic oligosaccharide derivatives representing different galactomannan fragments, demonstrated that mAb 8G4 could effectively recognize the parental pentasaccharide while mAb 7B8 recognizes its constituting trisaccharide parts. Immunofluorescence studies showed that both 7B8 and 8G4 could stain A. fumigatus cells in culture efficiently, but not the mutant strain lacking galactomannan. In addition, confocal microscopy demonstrated that Candida albicans, Bifidobacterium longum, Lactobacillus plantarum, and numerous gram-positive and gram-negative bacteria were not labeled by mAbs 7B8 and 8G4. The generated mAbs can be considered promising for the development of a new specific enzyme-linked assay for detection of A. fumigatus, which is highly demanded for medical and environmental controls.

Carboxymethyl konjac glucomannan - crosslinked chitosan sponges for wound dressing.

In this paper, carboxymethyl konjac glucomannan (CMKGM) was obtained by carboxyl modification of konjac glucomannan. Then CMKGM and chitosan (CS) were crosslinked and freeze-dried to prepare CMKGM/CS composite sponges with different proportions. The structure and micromorphology of CMKGM/CS sponges were investigated by FTIR spectroscopy and SEM. The SEM results showed that the pore structure of the composite sponge gradually increased with the increase of CMKGM content. To assess the applicability of CMKGM/CS composite sponges as wound dressing, the swelling behavior, water vapor transmission rate (WVTR), biocompatibility (cytotoxicity and hemolysis) were analyzed. The results indicated that CMKGM/CS composite sponges possessed high swelling ratio, proper WVTR and good biocompatibility, which might accelerate tissue regeneration. Meanwhile, in vivo experiments demonstrated that CMKGM/CS composite sponges could effectively heal full-layer wound of skin defects of male ICR mice.