Fabrication,characterization and in vivo evaluation of dexpanthenol sustained-release nanofibers for wound healing

In this study, wound dressings consisting of dexpanthenol (Dex)-loaded electrospun nanofibers were fabricated using polyvinyl alcohol (PVA)/sodium alginate (SA), and chitosan as the core and the shell, respectively. Considering the remarkable properties of chitosan, it was used as a shell against drug release and to improve the thermal stability, and tensile strength of the scaffold. By comparing the thermogravimetric, and tensile strength results of nanofibers with and without shell, it was revealed that the presence of chitosan in the shell side could improve the thermal stability and increased the tensile strength by about three times. The isotherm models of dexpanthenol release from the PVA/SA/Dex-CS scaffold was best described by the Langmuir model. Besides, Fourier transform infrared, scanning electron microscopy, and X-ray diffraction techniques were performed to characterize nanofibers. Furthermore, an in vivo investigation of a wound dressing with dexpanthenol showed better healing compared to the wound dressings without dexpanthenol.     

Evaluation and correlation of electrochemical and mechanical properties of PVA/SA nanofibres

The present study evaluates and correlates the morphology of poly (vinyl alcohol) (PVA) and sodium alginate (SA) nanofibres with their internal structure to determine dielectric and tensile properties for future applications as long-lasting and resistant cell scaffolds. This work generates electrospun nanofibres mixing SA concentration in a PVA solution cross-linked in calcium chloride media. The dielectric properties of the nanofibres that were obtained using electrochemical impedance spectroscopy (EIS) show that at higher amount of SA in the PVA/SA fibres, the cross-linking process occurs at shorter times, indicating the modification of the internal structure of the PVA/SA. The X-ray photoelectron spectra (XPS) demonstrate that the chemical composition of the nanofibres varies depending on the depth profile. The transmission electron microscopy (TEM) proves that the PVA/SA is formed as a core-shell coaxial nanofibre. The tensile testing demonstrates that with a higher SA concentration, the mechanical properties show brittleness.     

交联聚(N-异丙基丙烯酰胺)/(海藻酸钠/聚(N-异丙基丙烯酰胺))半互穿网络水凝胶的制备及其溶胀性能

将线性聚(N-异丙基丙烯酰胺)(PNIPAAm)和海藻酸钠(SA)分子同时引入到PNIPAAm凝胶中,制备了交联聚(N-异丙基丙烯酰胺)/(海藻酸钠/聚(N-异丙基丙烯酰胺))半互穿网络(Cr-PNIPAAm/(SA/PNIPAAm)semi-IPN)水凝胶。在弱碱性条件下(pH=7.4),改变SA与线性PNIPAAm的质量比对Cr-PNIPAAm/(SA/PNIPAAm)semi-IPN水凝胶的溶胀度没有太大的影响。在酸性条件下(pH=1.0),其溶胀度随着SA与线性PNIPAAm质量比的减小而增大。由于亲水性SA与线性PNIPAAm的协同作用,Cr-PNIPAAm/(SA/PNIPAAm)semi-IPN水凝胶的消溶胀速率得到很大提高。     

双极膜技术在电氧化制备3-甲基-2-吡啶甲酰胺中的应用

分别以戊二醛和Fe3+改性壳聚糖和海藻酸钠并分别与柔性链聚乙烯醇(PVA)共混, 制备了Fe-SA-CS-GA/PVA聚合物双极膜. 测定膜的红外光谱, I-V工作曲线, Na+与Cl-透过双极膜的迁移数, 离子交换容量及阴阳两极室中OH-及H+的变化, 并以扫描电镜观察膜表面和界面层形态. IR与接触角分析结果表明, CS经GA/PVA改性后其亲水性能得到显著提高. 将SA-CS/PVA双极膜及Nafion膜应用于电氧化制备3-甲基-2-吡啶甲酰胺. 实验结果表明, 以SA-CS/PVA双极膜为隔膜合成3-甲基-2-吡啶甲酰胺的产率达到49.8%, 高于以Nafion膜为隔膜的产率.与传统的的方法相比, 该方法的反应条件温和且能有效利用能源.     

m(SA-CS)BM串联电解槽双成对电解制备乙醛酸

分别用戊二醛和二价锡离子改性壳聚糖(CS)和海藻酸钠(SA),制备改性海藻酸钠/亮聚糖双极膜[m(SA-CS)BM].将其作为双阴阳极电解槽的隔膜,应用于双成对电合成乙醛酸体系.在电场的作用下,双极膜中水电离后生成的H+透过Msa阳离子膜进入阴极室,以补充草酸电还原生成乙醛酸过程中H+的消耗;OH-透过Mcs阴离子膜进入阳极室,与乙二醛电氧化生成乙醛酸过程中产生的H+结合生成H2O,以增大正向反应的速度.在电流密度为30mA/cm2,20℃下电解,双阴极室的电流效率分别可达86.94%和82.81%,双阳极室的电流效率可达81.99%和78.62%,电解电压稳定在3.0V左右.     

A study on the characterization and stability of rhenium(III) chloride-incorporated liposomes

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications through passive targeting tumor sites by enhancing permeability and retention effect. Radiolabeled liposomes have potential applications in radiotherapy and diagnostic imaging. However, the physico-chemical instability of liposomes during manufacturing and storage limits their extensive application. Therefore, considerable numbers of studies have been made on the stability of liposomes over the last few years in order to overcome this problem. In this study, we attempted to prepare polymer-coated liposomes using water-soluble chitosan in order to enhance the stability of rhenium(III) chloride-incorporated liposomes. They were characterized by an electrophoretic light-scattering spectrophotometer, Fourier transform infrared spectroscopy (FT-IR), UV–Vis spectrometer, and phase-contrast microscopy. The chitosan-coated liposomes are spherical and the particle size is about 800–850 nm. Incorporation of chitosan into the liposome bilayer decreased rhenium(III) chloride release from the liposome due to an increased rigidity of the liposome membrane structure. Chitosan-coated liposomes showed a higher stability compared with the stability of non-coated liposomes. The release characteristics of rhenium(III) chloride encapsulated in the liposome were taken as a measure of stability of the liposome membrane.     

Evaluation of single-point equations to determine intrinsic viscosity of sodium alginate and chitosan with high deacetylation degree

A viscometric study of two polyelectrolytes, chitosan (CH, with 94% deacetylation degree, in a solute-mixture of acetic acid (0.1 mol L⁻¹) and sodium chloride (0.2 mol L⁻¹) and sodium alginate (SA, with 62% M-units, in sodium chloride (0.1 mol L⁻¹), was performed at 25 °C. Five different equations were applied to calculate intrinsic viscosity [η]: Huggins, Kraemer and Schulz-Blaschke (SB) by graphical extrapolation; Solomon-Ciuta, Deb-Chanterjee and again SB, by faster single-point determination. Viscometric constants were calculated employing graphical extrapolation equations. Average molar mass (‾M_v) values were determined by applying the Mark-Houwink-Sakurada equation. For the samples analyzed, Huggins equation was the most suitable to calculate [η] and‾M_v by graphical extrapolation for chitosan, while Schulz-Blaschke and Solomon-Ciuta were adequate for single-point determinations of sodium alginate. Viscometric constants indicated that the aqueous mixture of acetic acid and sodium chloride is a poor solvent for chitosan, while sodium alginate is well solvated by aqueous sodium chloride.     

Caco-2细胞模型用于毒害污染物转运与吸收研究*

Caco-2 细胞来源于人类结肠癌细胞,其单层细胞模型常用于体外模拟肠道上皮细胞转运与吸收外源性物质的研究,并被广泛地应用于毒理学研究等方面。本文简要介绍了Caco-2 单层细胞模型的培养、细胞特性及常用功能指标;详细综述了环境毒害污染物在Caco-2细胞中转运与吸收机制以及污染物细胞毒性对其转运与吸收的影响,并对Caco-2 单层细胞模型在环境毒害污染物的人体健康风险评估中的应用进行了展望。     

Studies on Intestinal Transport of Ginsenoside Compatibility with Veratrum nigrum via Caco-2 Cell Monolayer Model Coupled with UPLC-ESI-MS Method

The Caco-2 cells have been recognized as effective tools to be applied to imitating the drug absorption in human intestine for the transport of drug. Herein, Caco-2 cell monolayer model was used to study the transport of the ginsenoside compatibility with Veratrum nigrum in different proportions. A specific high performance liquid chromatography-electrospray ionization-mass spectrometry(HPLC-ESI-MS) method was developed for the semiquantitative determination of ginsenoside in intestinal transport with Dioscin as an internal standard. For the Caco-2 model constructed, two influencing factors were investigated, including time and concentration. The results suggest that the absorption of ginsenoside Re, Rg1, Rb1, Rc, Rb2 and Rd are time- and concentration-dependent and the excretions of Rb1, Rc, Rb2 and Rd have a relatronship with some transport proteins. The bioavailability of the ginsenosides has reduced compared to the single Panax ginseng extract when compatibility with a certain amount of Veratrum nigrum.     

New polysaccharide-g-polyacrylonitrile copolymers: synthesis and thermal characterization

Various natural and modified polysaccharides (i.e. arabic gum, tragacanth gum, xanthan gum, sodium alginate, chitosan, sodium carboxymethyl cellulose, hydroxyethyl cellulose, methyl cellulose) were modified using ceric-initiated graft polymerization of acrylonitrile under inert atmosphere. Grafting was confirmed using spectral (FT-IR) proofs. The grafting parameters were determined by conventional methods. Thermal characteristics of the homopolymer-free copolymers were studied using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) under nitrogen atmosphere. The major thermal transitions as well as the activation energy of the major decomposition stages were investigated. The polyacrylonitrile (PAN)-grafted polysaccharides were recognized to be thermally stable more than the corresponding non-grafted substrates, although they begin to decompose at relatively lower temperatures than the non-grafted counterparts. Copyright © 2003 John Wiley & Sons, Ltd.     

Qualitative and Quantitative Analysis of Drug Interactions: Fritillary Mediating the Transport of Alkaloids in Caco-2 Cells by P-Glycoprotein

Ultra performance liquid chromatographic-electrospray ionization-mass spectrometry（UPLC-ESI-MS） was used to investigate the potential interaction between selected ingredients of Aconitum and fritillary. The efflux ratios of 14-benzoylmesaconine（BM）, 14-benzoylaconine（BC）, 14-benzoylhypaconine（BH）, mesaconitine（MA）, aco- nitine（AC） and hypaconitine（HA） was 11.16, 12.53, 11.69, 12.8, 11.03 and 6.15, respectively, and the secretion of them was inhibited by Veraparnil, which means they are the substrates of permeability-glycoprotein（P-gp）. The transport of Aconitum alkaloids extract through a Caco-2 cell monolayer was determined in the absence and presence of fritillary extract. And the fritillary extract increased the absorption of Aconitum alkaloids. Peimine（PE） and peimi- nine（PEN） in fritillary increased the absorption of pure Aconitum alkaloids. The transport of digoxin was respectively enhanced by PE and PEN, which means they are the inhibitors of P-gp. PEN showed more effective inhibition than PE at the same concentration. The in vitro data suggest that the compounds such as fritillary present in alkaloids were able to inhibit the P-gp activity and lead modifying the transport of alkaloids.     

Morphologic evolution of Au nanocrystals grown in ionic liquid by plasma reduction

By AFM we report the successful modulation of shell structure (morphology and shell thickness) of microcapsules through tailoring molecular substituents of chitosan. The shell thickness of hollow (HPCS/SA)(n) (n=5, 7, 9) capsules is more than 3 times that of the (QACS/SA)(n) (n=5, 7, 9) capsules, due to less charges carried by the neutral -NH(2) substituent group and the induced coily conformation in HPCS, while more charges carried by the positively charged -N(CH(3))(3)(+) substituent and the induced extended conformation in QACS (HPCS: hydroxyl propyl chitosan; QACS: quaternary ammonium chitosan; SA: sodium alginate). The ultrathin shells of microcapsules assembled in this work by the layer-by-layer (LbL) self-assembly technique rather than the traditional method of mixing CS, SA and CaCl(2) enable the thickness modulation characterization by AFM on the atomic scale. These microcapsules with tunable shell thickness provide important guidance for potential drug delivery and sustained release.     

Intensification of the Flotation Treatment of Water with Natural Polyelectrolytes

The influence of natural polyelectrolytes, sodium alginate and chitosan, on the efficiency of water treatment by flotation to remove fish oil was elucidated by studying the kinetics of formation of adsorption layers at the aqueous polyelectrolyte solution-air and aqueous polyelectrolyte solution-fish oil interfaces. The stability of fish oil emulsions stabilized by sodium alginate and chitosan was studied.     

Janus hydrogel with dual antibacterial and angiogenesis functions for enhanced diabetic wound healing

Anti-infection and neovascularization at the wound site are two vital factors that accelerate diabetic wound healing. However, for a wound healing dressing, the two functions need to work at different sites(inner and outer), giving big challenges for dressing design. In this study, we fabricated a novel sodium alginate/chitosan(SA/CS) Janus hydrogel dressing by the assembly of SA hydrogel loaded with silver nanoparticles(Ag NPs) and CS hydrogel impregnated with L-arginine loaded sodium alginate ...     

海藻酸-壳聚糖-海藻酸离子取代凝胶改性研究

羧甲基壳聚糖;微胶囊;海藻酸-壳聚糖-海藻酸离子取代凝胶改性研究     

Preparation of antimicrobial sodium alginate with chito-oligosaccharide side chains

To provide sodium alginate (SA) with an antimicrobial property, we introduced chito-oligosaccharide (COS) via chemical bonding in a two-step procedure. We reacted COS with N-methylol acrylamide (NMA) with N-methylol groups to prepare acrylamidomethyl chito-oligosaccharide (COS–NMA). SA with COS side chains (SA–COS) was produced through a subsequent reaction of SA with COS–NMA. The chemical structure of SA–COS was confirmed by IR spectroscopy and ¹H NMR spectroscopy. With a two-step method, we successfully prevented insoluble-complex formation due to electrostatic attraction between chitosan and alginate. SA–COS showed excellent antimicrobial activity, with the growth of microorganisms completely suppressed by a small amount of COS (1.8 wt %). © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1810–1816, 2001     

Increasing the throughput and productivity of Caco-2 cell permeability assays using liquid chromatography-mass spectrometry: application to resveratrol absorption and metabolism

The Caco-2 cell monolayer permeability assay has become a standard model of human intestinal absorption and transport. This paper reviews recent progress in increasing the throughput of Caco-2 cell monolayer assays and in expanding the scope of this assay to include modeling intestinal drug metabolism. The state-of-the-art in Caco-2 cell monolayer permeability assays combines multi-well plates fitted with semi-permeable inserts on which Caco-2 cells have been cultured with liquid chromatography-mass spectrometry (LC-MS) or LC-tandem mass spectrometry (LC-MS-MS) for the quantitative analysis of test compounds and the identification of their intestinal metabolites. After reviewing the progress in increasing the throughput of Caco-2 cell monolayer assays for both modeling human intestinal permeability or transport and the metabolism of xenobiotic compounds, we demonstrate the application of LC-MS and LC-MS-MS to the measurement of resveratrol permeability and metabolism in the Caco-2 model. trans-Resveratrol (trans-3,5,4'-trihydroxystilbene) is a polyphenolic compound occurring in grapes, peanuts and other food sources, that is under investigation as a cancer chemoprevention agent. The apparent permeability coefficient for apical (AP) to basolateral (BL) movement of resveratrol was 2.0 x 10(-5)cm/sec. Resveratrol was not a substrate for P-glycoprotein or the multi-drug resistance associated proteins (MRP). No phase I metabolites were observed, but the phase II conjugates resveratrol-3-glucuronide and resveratrol-3-sulfate was identified based on LC-MS and LC-MS-MS analysis and comparison with synthetic standards. Although these data indicate that resveratrol diffuses rapidly across the intestinal epithelium, extensive phase II metabolism during absorption might reduce resveratrol bioavailability.     

Preparation and pharmaceutical evaluation of liposomes entrapping salicylic acid/gamma-cyclodextrin conjugate

To evaluate the potential use of a drug/cyclodextrin (CyD) conjugate for efficient entrapment in liposomes and prolonged residence of a drug in tissues, we synthesized a salicylic acid (SA) conjugate bound covalently with gamma-cyclodextrin (SA/gamma-CyD conjugate), a model drug/CyD conjugate, and then liposomes entrapping the conjugate (conjugate-in-liposome) were prepared by a freezing-thawing method. The chemical and physicochemical properties of the SA/gamma-CyD conjugate in solution and solid state were investigated and then the physicochemical properties of conjugate-in-liposome, in vitro cellular uptake/release and in vivo disposition of SA/gamma-CyD conjugate after intravenous administration of aqueous suspension containing conjugate-in-liposome in rats, were evaluated, comparing with those of the liposome-entrapped SA alone (SA-in-liposome) or the liposome-entrapped noncovalent SA/gamma-CyD complex (complex-in-liposome). As a result, it was found that the conjugate was amorphous powder and the release of SA from the conjugate in phosphate-buffered saline (PBS) was tolerated to chemical and enzymatic degradation. Meanwhile, the particle sizes and stability of these liposomes were almost identical, and the entrapment ratio of SA/gamma-CyD conjugate in liposomes was higher than those of SA alone and SA/gamma-CyD complex. The cellular uptake of these liposomes was almost equivalent, but the release of SA/gamma-CyD conjugate from RAW264.7 cells was markedly slower, compared with that of SA from cells following cellular uptake of the SA-in-liposome and complex-in-liposome. The disposition of SA or SA/gamma-CyD conjugate following intravenous administration of aqueous suspensions containing each liposome system in rats was comparable, but the residence time of the conjugate in tissues significantly prolonged, compared with that of the SA-in-liposome and complex-in-liposome systems. These results suggest the potential use of SA/gamma-CyD conjugate for efficient entrapment in liposomes as well as of liposomes containing SA/gamma-CyD conjugates for prolonged residence of drugs in tissues.     

海藻酸钙-壳聚糖微胶囊组成对BSA通透性能影响的研究

对海藻酸钙-壳聚糖微胶囊的牛血清白蛋白(BSA)双向通透性能进行了定量和定性的初步研究, 并初步考察了微胶囊的组成成分及海藻酸钠、壳聚糖的溶液浓度对BSA通透性能的影响. 结果表明海藻酸钙-壳聚糖微胶囊在pH 1.5～2.0时通透性减弱, pH 6.8时通透性增强, 且海藻酸钙微胶囊通透性大于海藻酸钙-壳聚糖微胶囊; 海藻酸钙-壳聚糖微胶囊中壳聚糖浓度越小, 通透性越好; 海藻酸钠浓度的影响不显著.     

Determination of in vitro permeability of drug candidates through a caco-2 cell monolayer by liquid chromatography/tandem mass spectrometry

Studying the permeability of compounds across a Caco-2 cell monolayer is an established in vitro model to screen for oral absorption and to evaluate the mechanism of transport. This assay can also be used to evaluate compounds as potential P-glycoprotein substrates and/or inhibitors. The traditional methods of sample analysis (high-performance liquid chromatography (HPLC) with a UV or fluorescence detector) limit the throughput and sensitivity of this assay. Data are presented here describing the use of liquid chromatography/tandem mass spectrometry (LC/MS/MS) for the analysis of samples derived from the Caco-2 cell studies. During the analysis an automatic switching valve was used to divert the flow from the HPLC column to waste for the first minute, preventing the early eluting salts from entering and contaminating the LC/MS interface. This approach allows the rapid and accurate determination of drug transport across the Caco-2 cell monolayer. The high sensitivity and specificity of LC/MS/MS make this technique an ideal candidate for the low concentration and high throughput routine analysis of Caco-2 cell solutions, especially if multiple compounds are administered and analyzed simultaneously. Thus, the use of LC/MS/MS will increase the value of the Caco-2 cell assay as an in vitro screening tool.