Urinary (1)H-NMR metabonomics study on intervention effects of soya milk in Africans.

Metabonomics is an important tool in understanding the toxicological or therapeutic effects of interventions by analysing metabolic profiles and interpreting complex multi-dimensional spectroscopic/spectrometric data using multivariate data analysis. The objectives of this study were to evaluate the metabolic changes following a short-term 5 day soya milk intervention, and to investigate factors that influence soy-phytoestrogen metabolism focused on Africans based in either UK or Nigeria. (1)H-NMR metabonomics was applied to analyse urine samples collected at four phases I-IV (pre, days 3 and 5, and post) of the soy-intervention from African volunteers (n = 40 in total). Individual proton NMR spectra were visually and statistically assessed using multivariate analyses (MVA): principal component analysis (PCA) and (orthogonal-) partial-least square-discriminant analysis ((O-) PLS-DA). In addition, 22 endogenous metabolites were quantified using a Chenomx NMR suite. The results showed the levels of analysed endogenous metabolites (creatinine adjusted) present ranged from 4 µM to 12 mM with large inter-subject variances in acetate, acetone, lactate and trimethylamine. The MVA results showed high inter-individuality and sampling variances based on PCA score plots, and demonstrated soy metabolism to be significantly influenced by location and gender by both PLS-DA and O-PLS-DA.

Polyacrylonitrile nanofibers prepared using coaxial electrospinning with LiCl solution as sheath fluid.

A modified coaxial electrospinning process including an electrolyte solution as sheath fluid was used for preparing high quality polymer nanofibers. A series of polyacrylonitrile (PAN) nanofibers were fabricated utilizing a coaxial electrospinning containing LiCl in N, N-dimethylacetamide (DMAc) as the sheath fluid. FESEM results demonstrated that the sheath LiCl solutions have a significant influence on the quality of PAN nanofibers. Nanofibers with smaller diameters, smoother surfaces and uniform structures were successfully prepared. The diameters of nanofibers were controlled by adjusting the conductivity of the sheath fluid over a suitable range and this was determined by varying LiCl concentrations. The influence of the effect of LiCl on the formation of PAN fibers is discussed and it is concluded that coaxial electrospinning with electrolyte solutions is a convenient and facile process for achieving high quality polymer nanofibers.

Improving polymer nanofiber quality using a modified co-axial electrospinning process.

Based on a modified coaxial electrospinning process and suitable selection of solvent mixtures as sheath fluid, a new strategy is presented for systematically improving polymer nanofiber quality. A concentric spinneret with an indented inner capillary is designed for the modified coaxial electrospinning. With a solution of 12% w/v PVP K60 in ethanol as the core electrospinning fluid, six solvents are used as sheath fluids to investigate the impact of solvent properties on the resultant PVP nanofiber quality. The PVP nanofiber quality is closely related to solvent physical-chemical properties. High quality PVP nanofibers of average diameter 130 ±10 nm with homogeneous structures and smooth surfaces are created using a solvent mixture of acetone, ethanol and DMAc in the ratio of 3:1:1(v/v/v).

Multicomponent amorphous nanofibers electrospun from hot aqueous solutions of a poorly soluble drug.

PURPOSE: To design and fabricate multicomponent amorphous electrospun nanofibers for synergistically improving the dissolution rate and permeation profiles of poorly water-soluble drugs. METHODS: Nanofibers were designed to be composed of a poorly water soluble drug, helicid, a hydrophilic polymer polyvinylpyrrolidone as filament-forming matrix, sodium dodecyl sulfate as transmembrane enhancer and mannitol as taste masking agent, and were prepared from hot aqueous co-dissolving solutions of them. An elevated temperature electrospinning process was developed to fabricate the composite nanofibers, which were characterized using FESEM, DSC, XRD, ATR-FTIR, in vitro dissolution and permeation tests. RESULTS: The composite nanofibers were homogeneous with smooth surfaces and uniform structure, and the components were combined together in an amorphous state because of the favorable interactions such as hydrogen bonding, electrostatic interaction and hydrophobic interactions among them. In vitro dissolution and permeation tests demonstrated that the composite nanofibers had a dissolution rate over 26-fold faster than that of crude helicid particles and a 10-fold higher permeation rate across sublingual mucosa. CONCLUSIONS: A new type of amorphous material in the form of nanofibers was prepared from hot aqueous solutions of multiple ingredients using an electrospinning process. The amorphous nanofibers were able to improve the dissolution rate and permeation rate of helicid.

Ester prodrug-loaded electrospun cellulose acetate fiber mats as transdermal drug delivery systems.

Cellulose acetate (CA) fibers loaded with the ester prodrugs of naproxen, including methyl ester, ethyl ester and isopropyl ester, were prepared through electrospinning using acetone/N,N-dimethylacetamide(DMAc)/ethanol (4:1:1, v/v/v) as solvent. The chemical and morphological characterizations of the medicated fibers were investigated by means of SEM, DSC, XRD and FTIR, as well as the studies of the drug release properties. The results indicated that the morphology and diameter of the fibers were influenced by the concentration of spinning solution, applied voltage, electrospun solvent and the surfactants. The average diameters of the fibers ranged between 100 and 500 nm for three prodrugs. There was good compatibility between CA and three prodrugs in the blended fibers, respectively. In vitro release indicated that constant drug release from the fiber was observed over 6 days. The prodrugs were successfully encapsulated into the fibers, and this system was stable in terms of effectiveness in release.

Dissolution improvement of electrospun nanofiber-based solid dispersions for acetaminophen.

The objective of the present investigation was to prepare novel solid dispersions (SDs) of poorly water-soluble drugs with special microstructural characteristics using electrospinning process. With the hydrophilic polymer polyvinylpyrrolidone as the filament-forming polymer and acetaminophen (APAP) as the poorly water-soluble drug model, SDs having a continuous web structure, and in the form of non-woven nanofiber membranes, were successfully prepared. The electrospun nanofiber-based SDs were compared with those prepared from three traditional SD processes such as freeze-drying, vacuum drying, and heating drying. The surface morphologies, the drug physical status, and the drug-polymer interactions were investigated by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction, and attenuated total reflectance Fourier transform infrared. In vitro dissolution tests demonstrated that the electrospun nanofibers released 93.8% of the APAP content in the first 2 minutes and that the dissolution rates of APAP from the different SDs had the following order: electrospun membrane > vacuum-dried membrane approximately freeze-dried membrane > heat-dried membrane. Electrospun nanofiber-based SDs showed markedly better dissolution-improving effects than the other SDs, mainly due to their huge surface area, high porosity resulting from web structure, and the more homogeneous distribution of APAP in the nanofiber matrix.

Arachidonic and docosahexaenoic acid deficits in preterm neonatal mononuclear cell membranes. Implications for the immune response at birth.

Preterm neonates are more susceptible to infection than term neonates. Arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) are biologically active components of cell membrane phospholipids. Arachidonic acid is a substrate for the synthesis of eicosanoids, potent regulators of immune function. Preterm babies may have a deficiency of arachidonic acid and docosahexaenoic acid, but the impact of this deficit on maturation of the immune system is unknown. To address this we explored links between placental provision of fatty acids to cord blood mononuclear cell (CBMC) membranes using gas chromatography (GC), and maturation of the immune response with gestational age by analysing lymphocyte subsets by flow cytometry. This is the first study to examine the lipid profile of the phosphatidylcholine (PC) and phosphatidylethanolamine (PE) fractions of CBMC membranes from preterm neonates. The long chain polyunsaturated fatty acid (LCPUFA) composition of CBMC membranes was dominated by arachidonic acid in both PE (34%) and PC (15%) fractions in healthy term neonates (> or =37 weeks, n=9), whilst in healthy preterm neonates (<37 weeks, n=10) the level of arachidonic acid was significantly lower at 28.8% and 12.5% respectively (p<0.05). Preterm neonates (<37 weeks, n=23) also had significantly lower absolute numbers of CD4+ (p<0.05) leukocytes and CD4+ (p<0.01) and CD8+ (p<0.05) naïve T-cells than term (> or =37 weeks, n=24) neonates that correlated with gestational age (p<0.01-0.05).

Sulfated beta-glucan derived from oat bran with potent anti-HIV activity.

China is a major producer of oats; the annual harvested area of 350,000 ha yields approximately 465,000 tons, giving an average yield of 1.33 tons/ha. The bran is not used for animal feed as it is of poor digestibility and low nutritive content and is considered a waste byproduct. Therefore, it is advantageous to produce a value-added product from the bran. We extracted the native polysaccharide, a linear (1-3)-, (1-4)-linked beta-glucan (OBG) from the oat bran and synthesized a sulfated derivative OBGS containing 36.5% sulfate. OBGS had potent activity against a primary isolate of human immunodeficiency virus (HIV-1) in peripheral blood mononuclear cells at a concentration (EC(50)=5.98 x 10(-4) microM) approximately 15,000 times below its cytotoxic concentration. OBGS was also active postinfection (EC(50)=5.3 x 10(-4) microM) and protected pretreated peripheral mononuclear cells (EC(50)=5.2 x 10(-2) microM) washed free of the compounds prior to infection. Thus, OBGS has potential as a vaginal microbicide and is the first such report for oat bran derived sulfated beta-glucan.

Removal of Cu2+ from aqueous solution by adsorption onto a novel activated nylon-based membrane.

A novel activated nylon-based membrane was prepared and applied as an adsorbent for the removal of Cu2+ from aqueous solutions. It involved three stages: (i) deposition of a chitosan layer that functionalized the nylon membrane, (ii) cross-linking with epichlorohydrin to stabilize the polymer layer and enabling grafting, and (iii) iminodiacetic acid grafting. SEM and EDX techniques were used to characterize the composition of the membranes. Dynamic adsorption experiments on membranes were carried out at various pH values, contact times, adsorption dosages and initial metal concentrations to determine optimum membrane adsorption properties. The adsorption isotherm relating to Cu2+ fitted the Langmuir equation and an adsorption equilibrium constant and adsorption capacity of 2.345x10(-3)mg/ml and 10.794mg/g were determined, respectively. The experimental data was analyzed using two adsorption kinetic models, pseudo-first-order and pseudo-second-order with the latter system providing the best fit. Finally complete regeneration of the activated nylon membrane was possible using 100mmol/l Na2EDTA.

Pharmacokinetics and bioavailability of gentiopicroside from decoctions of Gentianae and Longdan Xiegan Tang after oral administration in rats--comparison with gentiopicroside alone.

The pharmacokinetics and bioavailability of gentiopicroside (GPS), an active component of the Gentian plant species, from orally administered decoctions of Gentianae (DG), or in combination with other plants in the prescription of Longdan Xiegan Tang (LXT), was compared in rats with oral administration of GPS alone, using doses adjusted to deliver equivalent amounts of GPS (150 mg/kg). Changes in plasma levels of GPS following oral administration of GPS or DG could be fitted to a one compartment open model with elimination half times (T(1/2)Ke) of 3.35+/-0.76 h and 6.21+/-3.07 h, respectively. Kinetics of plasma GPS following oral administration of LXT could be fitted to a two compartments open model with an elimination half time (T((1/2)beta)) of 3.83+/-1.54 h. The bioavailability of GPS from DG was markedly better, and that from LXT markedly worse, compared with GPS alone, as judged by the area under concentration-time curve (AUC) values of 70.0+/-13.9 microgh/ml (DG), 32.7+/-12.9 microgh/ml (GPS) and 19.1+/-5.9 microgh/ml (LXT). The study demonstrates the marked variability in pharmacokinetics and bioavailability of an active component from different herbal preparations.

Pharmacokinetic behavior of gentiopicroside from decoction of Radix Gentianae, Gentiana macrophylla after oral administration in rats: a pharmacokinetic comaprison with gentiopicroside after oral and intravenous administration alone.

The pharmacokinetics in rats of gentiopicroside (GPS) from orally administered decoctions of Radix Gentianae (DRG) and Gentiana macrophlla (DGM) were compared with that of GPS alone administered at 150 mg/kg orally and 30 mg/kg intravenously. The metabolic profile of GPS after intravenous injection could be fitted to two-compartment model whereas oral administration decoctions DRG or DGM, or GPS alone, could all be fitted to a one-compartment model. After oral administration of GPS alone, GPS was absorbed quickly and reached a maximum plasma concentration (Cmax) value, 5.78 +/- 2.24 microg/mL within 0.75 +/- 0.62 h. The plasma level of GPS declined with a T1/2ke, 3.35 +/- 0.76 h. After oral administration of decoctions DRG and DGM, GPS was absorbed and reached significantly higher maximum concentrations of 10.53 +/- 3.20 microg/mL (p < 0.01) and 7.43 +/- 1.64 microg/mL (p < 0.05) at later time points 1.60 +/- 0.76 (p < 0.01) and 2.08 +/- 0.74 h (p < 0.05), for DRG and DGM respectively, compared with oral GPS alone. Significantly larger AUC values were found for decoctions of GPS (83.49 +/- 20.8 microgxh/mL for DRG and 59.43 +/- 12.9 microgxh/mL for DGM) compared with oral GPS alone (32.67 +/- 12.9 microgxh/mL). The results demonstrate that the bioavailability of GPS was markedly improved when administered as a decoction than as purified GPS. The decoction from Radix Gentianae provided 2.5 times better bioavailability and that from Gentiana macrophlla 1.8 times higher. The study confirms the importance of careful pharmacokinetic analysis in the characterization of herbal medicines when applied for future clinical applications.

Preparation and characterization of a novel sodium alginate incorporated self-assembled Fmoc-FF composite hydrogel.

Dipeptides and their derivatives have attracted tremendous attention owning to their excellent abilities of self-assemble assembling into various structures which have great potentials for applications in biology and/or nanotechnology. In the present study, we dedicate to fabricate a rigid and structure controllable Fmoc-FF/SA composite hydrogel. We found that the modified dipeptide, fluorenyl-9-methoxycarbonyl (Fmoc)-diphenylalanine (Phe-Phe) can self-assemble into rigid hydrogels with structures of nanowires, layered thin films or honeycombs as the change of sodium alginate (SA) concentration. Meanwhile, CD-spectroscopy demonstrated that SA appeared to control the process, but it did not change the arrangement of the Fmoc-FF peptide. Our results demonstrated that the formed hydrogel showed physical and chemical stability as well as possessing good biocompatibility. Rheological measurements showed that the addition of SA could improve the stability of the hydrogel. Cell viability assay revealed that the Fmoc-FF and Fmoc-FF/SA hydrogels are both beneficial for cell proliferation in-vitro. Our results indicated that the fabricated Fmoc-FF/SA composite hydrogels could be used in tissue engineering and drug delivery in the future.

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation.

In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections. Reduced blood sugar levels were seen in the microsphere treatment groups, with the results being similar to those obtained with conventional injections between 10 and 25days after the commencement of treatment. After 5 and 30days of treatment, the microspheres seem a little slower to act than the injections. The pathology of the rats' spleen, heart, kidney and lungs was probed after the 30-day treatment period, and the results indicated that the microspheres were safe and had beneficial effects on the liver, reducing the occurrence of fatty deposits seen in untreated diabetic rats. Moreover, in terms of liver, renal and cardiac functions, and blood lipid and antioxidant levels, the microspheres were as effective as the injections. The expression of several proteases linked to the metabolism of aliphatic acids and homocysteine was promoted by the microsphere formulations. Inflammatory markers in the microsphere treatment groups were somewhat higher than the injection group, however. The liraglutide/PLGA microspheres prepared in this work are overall shown to be efficacious in a rat model of diabetes, and we thus believe they have strong potential for clinical use.

Efficacy of Rhizophora mangle aqueous bark extract (RMABE) in the treatment of aphthous ulcers: a pilot study.

OBJECTIVE: Rhizophora mangle aqueous bark extract (RMABE) (CIKRON-H), has been used as antiseptic and skin wound healing promoter. The present study was a randomised, single-blinded, placebo control trial conducted to asses the efficacy of RMABE in treating oral aphthous ulcers. RESEARCH DESIGN AND METHODS: Patients (n = 32) with aphthous ulcers were randomised to received placebo solution or RMABE topically, once a day, from Monday to Friday, until they healed. The efficacy of the treatment was evaluated by physician clinical observations (time to heal, change in condition), the quality of the patient's life and the tolerability through recording adverse effects. RESULTS: No demographic differences were noted between the two groups at base-line. Seven days after treatment, 12 of the 17 patients in the RMABE group (71%) were completely healed of their aphthous ulcers, with repaired mucosa and no symptoms of ulcers, compared with one in 15 patients in the placebo group (7%) (p < 0.0001). The time taken for the signs and symptoms of ulcers to diminish was also higher in the placebo than in RMABE-treatment group (erythema: placebo 10.54 +/- 1.24, RMABE 4.94 +/- 0.72 days, p = 0.0003; ardour: placebo 7.00 +/- 0.76, RMABE 2.93 +/- 0.49 days, p = 0.0001; and pain: placebo 7.43 +/- 1.21, RMABE 2.92 +/- 0.23 days, p = 0.0011). No subject showed any sign of adverse effects. CONCLUSIONS: These observations demonstrate that the R. mangle aqueous bark extract reduced the time to repair mucosal tissue, erythema, ardour and pain persistence. There was no evidence any adverse effects. This is the first time that the R. mangle extract has been reported to have mouth mucosa healing properties.

Fabrication of glycopolymer/MWCNTs composite nanofibers and its enzyme immobilization applications.

Glycopolymer (poly(AN-co-OVSEG))/MWCNTs (multiwalled carbon nanotubes) composite nanofibers are fabricated using a facile approach combining enzymatic synthesis, radical polymerization and electrospinning. The structure of the glycopolymer was confirmed by FT-IR and (1)H NMR. Poly(AN-co-OVSEG)/MWCNTs composite nanofibers were prepared using electrospinning and characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The hydrophilic properties of the composite nanofibers surfaces were increased since the contact angle of poly(AN-co-OVSEG)/MWCNTs composite was reduced from 65.5° to 37° compared to (PAN). As an enzymatic model catalase (CAT) was loaded (ca. 55.0mg/g) to the poly(AN-co-OVSEG)/MWCNTs nanofibers. The optimum temperature for poly(AN-co-OVSEG)/MWCNTs nanofibers increased from 25°C to 45°C compared to free CAT. The covalently immobilized enzymes conjugate exhibited 60% activity at 60°C, while the free enzyme was entirely inactivity after 5min heat treatment. The immobilized CAT retained 70% of its initial activity after 5 cycles of decomposition of hydrogen peroxide.

Fabrication and aggregation of thermoresponsive glucose-functionalized double hydrophilic copolymers.

Novel double-hydrophilic thermosensitive statistical glycopolymers, poly(N-isopropylacrylamide-co-6-O-vinyladipoyl-D-glucose), were fabricated using a chemoenzymatic process and free radical copolymerization. The structures of the glycopolymers were confirmed by (1)H and (13)C NMR, and their molar mass distributions determined by gel permeation chromatography. UV-vis spectroscopy data showed that the polymers exhibited reproducible temperature-responsive behavior. The self-assembly and critical aggregation concentration was verified by fluorescence spectroscopy with pyrene acting as a hydrophobic probe. Measurements by laser light scattering and transmission electron microscopy revealed that the glycopolymers were able to self-assemble into aggregates with varying particle sizes and morphologies in aqueous solutions.

Electrospun nanofibers in drug delivery: recent developments and perspectives.

In this review article, some key challenges in drug delivery are first introduced and methods that have been applied in attempts to solve them enumerated. Particularly intractable problems are highlighted: these include issues of solubility, targeting and drug degradation. The technique of electrospinning is subsequently introduced, and the influence of processing parameters on the fibers produced discussed. The potential of electrospun nanofibers in drug delivery is then explored, with examples given from the recent literature to illustrate how fibers can be used to overcome hurdles in drug solubility, degradation and targeting. Future perspectives and challenges are also considered.

A systematic study of captopril-loaded polyester fiber mats prepared by electrospinning.

In this study, drug-loaded nanofibers were prepared by electrospinning captopril (CPL) with aliphatic biodegradable polyesters. Poly(L-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA), and poly(lactic-co-ε-caprolactone) (PLCL) were used as filament-forming matrix polymers, and the concentration of CPL in each fiber type was varied. Scanning electron microscopy indicated that the morphology and diameters of the fibers were influenced by the concentration of polymer in the spinning solution and the drug loading. CPL was found to be distributed in the polymer fibers in an amorphous manner using differential scanning calorimetry and X-ray diffraction. FTIR indicated that hydrogen bonding existed between the drug molecules and the carrier polymers. In vitro dissolution tests showed that drug release from the fibers was highly dependent on the release medium, temperature, and on the polymer used. A range of kinetic models were fitted to the drug-release data obtained, and indicated that release was diffusion controlled in all cases. The different polymer fibers have application in diverse areas of drug delivery, for instance as sub-lingual or sustained release systems. Furthermore, by combining different CPL-loaded fibers, it would be possible to produce a bespoke formulation with tailored drug-release properties.

Time-engineeringed biphasic drug release by electrospun nanofiber meshes.

A drug-loaded nanofiber mesh which could achieve time-engineeringed biphasic release was fabricated through sequential electrospinning. The drug to polymer ratio of each single mesh was allocated and designed before the tri-layered meshes were created. The resultant meshes had the following construction: (i) the first drug-loaded mesh (top side), (ii) the second drug-loaded mesh (second side), and (iii) the third drug-loaded mesh (bottom side). The drug release speed and duration were controlled by designing morphological features of the electrospun meshes such as the fiber diameter and mesh thickness. An in vitro release experiment revealed that the tri-layered construction with distinct morphological features of each component mesh can provide biphasic drug release. The time-engineeringed dual release system using the multilayered electrospun nanofiber meshes was proved to be a useful formulation when achieving controlled drug release at different times.

Antitumor activity of Dioscorea bulbifera L. rhizome in vivo.

Antitumor activities of water extract (fraction A), ethanol extract (fraction B), ethyl acetate extract (fraction C), non-ethyl acetate extract (fraction D) and compound diosbulbin B isolated from Dioscorea bulbifera L. (DB) were investigated in vivo in this present study. The results showed that fractions B and C both decreased tumor weight in S180 and H22 tumor cells bearing mice, while fractions A and D had no such effect. Furthermore, fraction C altered the weight of spleen and thymus, and the amounts of total leukocytes, lymphocytes and neutrophils in tumor-bearing mice. Further results showed that compound diosbulbin B demonstrated anti-tumor effects in the dose-dependent manner at the dosage of 2 to 16 mg/kg without significant toxicity in vivo. Furthermore, on the basis of chemical analysis of the above extracts by high-performance liquid chromatography (HPLC) with a diode array detector (DAD), diosbulbin B was found to be the major antitumor bioactive component of DB. These results suggest that DB has potential anti-tumor effects which may be related to influencing the immune system for the first time, and the compound diosbulbin B is the major antitumor component of DB.