Possibility of Targeting Treatment for Ischemic Heart Disease With Liposome(Ⅱ)

Studies on the isolated rat heart perfusion model have proved that perfusion with high Ca_(2+) (4.5 mmol/L), high K~+ (8.7 mmol/L) or tree radical generating system (FRGS) significantly increases myocardial uptake of liposomes. Intravenous injection of liposomes covalently combined with antibody of rat myocardial cells obviously elevates the target action of liposomes to myocardium. Liposome-carried SOD for treatment of rat myocardial ischemia-repertusion injury is much more effective than simple SOD. The results evidence that the liposome as drug carrier for treatment of ischemic heart diseases shows a broad prospect for its clinical use.     

Synthesis Hexadecyl 3-{4-[2-Hydroxy-3（isopropylamino）propoxy]phenyl}propionate as Potential Ligand for Liposome Targeting to Ischemic Myocardium

Novel hexadecyl 3- { 4-[2-hydroxy-3（isopropylamino）propoxy]phenyl }propionate （HPP）was synthesized and its effect on delivery of liposomes into cultured cardiomyocytes was examined. The structure of HPP was characterized by IH NMR, 1R and MS. The amount of cardiomyocytes uptake of HPP-liposome was 3.9-fold higher than plain-liposome, and the increase was 6.2-fold when hypoxia happens. It indicated that HPP was a potential ligand for liposome targeting to ischemic myocardium.     

Recognition of Biotin－functionalized Liposomes

Functionalized liposomes were prepared by mixing the biotin in the lipid vesicle suspensions. The experiments through immersing streptavidin deposited mica into the biotin modified liposome solution testify the specifically biological binding interaction and extend the function of liposomes as a biosensor or drug carrier.     

The preparation of cationic folic acid and its application in drug delivery system

The cationic folic acid（CFA） was prepared by introducing triethylenetetramine into folic acid with EDCI/NHS and characterized by IR, NMR and mass spectra. It was found that approximately one of two carboxyls in the folic acid molecule was substituted to form CFA. The conversion of γ-carboxyl is found to be 59% higher than 30% of γ-carboxyl. The CFA and doxorubicin hydrochloride can be loaded on the ionic shell of PTX-encapsulated micelle to form CFA loaded binary drug carrier via static interaction in aqueous solutions. The successful loading was demonstrated by zeta potential measurement and the drug load amount（DLA） of CFA was measured by HPLC. In vitro cytotoxicity results revealed the CFA drug carrier showed higher cytotoxicity to cancer cell MDA-MB-321 than the binary drug carrier without CFA and the positive control, while it showed lower cytotoxicity to normal cell HUVEC than the positive control, and similar cytotoxicity with the binary drug carrier without CFA. These results as well as confocal laser scanning microscopy observation indicate the synthesized CFA drug carrier possesses active tumor-targeting property.     

Endogenous nucleotide as drug carrier: base-paired guanosine-5′-monophosphate:pemetrexed vesicles with enhanced anticancer capability

Endogenous substance such as nucleotide as a drug carrier has been proposed as a novel drug delivery system.The nucleotide guanosine-5’-monophosphate(GMP) is used to transport an anticancer drug pemetrexed disodium heptahydrate(PMX) via specific base pairing.The endogenous nature of GMP helps to avoid biocompatibility issues that are generally accompanied with nanocarriers including cytotoxicity,immunogenicity and blood compatibility.Furthermore,the low-molecular weight of the GMP nucleotide carrier significantly boosts the drug loading capacity compared to traditional liposomes and high-molecular weight carriers.Hydrogen-bonding interaction between the carrier and drug realizes the controlled release of loaded drug,and also facilitates large scale manufacture since no additional chemical synthesis is required.More importantly,in vivo experiments reveal that the base-paired GMP:PMX nanovesicles improve the target specificity and pharmacokinetic properties of PMX,and exhibit remarkably enhanced anticancer abilities compared to standalone PMX without any carriers.We envision that this strategy could be extended to other endogenous substances and drugs bearing functional groups capable of specific interaction,and promote the construction of drug delivery systems with inherent biocompatibility,enhanced drug delivery efficacy,and a simplified preparation method.     

Lipase-catalyzed synthesis of novel galactosylated cholesterol

In an organic phase system,an enzymes lipase was used as a catalyst to synthesize galactosylated cholesterol,(5-cholesten-3b-yl)[(4-O-β-D-galactopyranosyl)D-glucitol-6]sebacate(CHS-SE-LA),which contains galactose residues.Its chemical structure was characterized by ESI-MS,and NMR.For HepG2 cells,the cellular fluorescence intensities of liposomes modified with CHS-SE-LA(GAL-FL) were as much as 2.6-fold(p 0.01) control liposomes(FL).Moreover,the presence of excess galactose significantly inhibited the uptake of GAL-FL suggesting ASGPR mediated uptake.In conclusion,the novel galactosylated ligand CHS-SE-LA was synthesized by lipase-catalyzation and revealed a great potential as drug carrier materials for hepatocyte-selective targeting.     

Chemical-looping gasification of biomass in a 10 kW_(th) interconnected fluidized bed reactor using Fe_2O_3/Al_2O_3 oxygen carrier

Abstract:The aim of this research is to design and operate a 10 kW hot chemical-looping gasification(CLG)unit using Fe2O3/Al2O3as an oxygen carrier and saw dust as a fuel.The effect of the operation temperature on gas composition in the air reactor and the fuel reactor,and the carbon conversion of biomass to CO2and CO in the fuel reactor have been experimentally studied.A total60 h run has been obtained with the same batch of oxygen carrier of iron oxide supported with alumina.The results show that CO and H2concentrations are increased with increasing temperature in the fuel reactor.It is also found that with increasing fuel reactor temperature,both the amount of residual char in the fuel reactor and CO2concentration of the exit gas from the air reactor are degreased.Carbon conversion rate and gasification efficiency are increased by increasing temperature and H2production at 870℃reaches the highest rate.Scanning electron microscopy(SEM),X-ray diffraction(XRD)and BET-surface area tests have been used to characterize fresh and reacted oxygen carrier particles.The results display that the oxygen carrier activity is not declined and the specific surface area of the oxygen carrier particles is not decreased significantly.     

Electronic Properties of Armchair Graphene Nanoribbons with Oxygen-terminated Edges: A Density Functional Study

Armchair graphene nanoribbons with different proportions of edge oxygen atoms are analyzed in this study using the crystal orbital method,which is based on density functional theory.Although buckled edges are present,all the nanoribbons are energetically favorable.Unlike the adjacent edge oxygen atoms,the isolated edge oxygen atoms cause semiconductor-metal transitions by introducing edge states.For graphene nanoribbons with all oxygen atoms on the edges,band gap and carrier mobility vary with ribbon width.Furthermore,this behavior is different from that of hydrogen-passivated graphene nanoribbons because of different effective widths,which are pictorially presented with crystal orbitals.The carrier mobilities are as 18%~65% magnitude as those of hydrogen-passivated nanoribbons and are of the order of 103 cm2·V-1·s-1.     

Preparation and characterization of m PEG grafted chitosan micelles as 5-fluorouracil carriers for effective anti-tumor activity

The objective of this study was to investigate the potential of methoxy polyethylene glycol（m PEG）grafted chitosan（m PEG-g-CS） to be used as a drug carrier. m PEG-g-CS was successfully synthesized by one-step method with formaldehyde. The substitution degree of m PEG on chitosan was calculated by elemental analysis and was found to be（3.23 0.25）%. m PEG-g-CS self-assembled micelles were prepared by ultrasonic method with the controlled size of 178.5–195.1 nm and spherical morphology. Stable dispersion of the micelles was formed with the zeta potential of 2.3–30.2 m V. 5-Fluorouracil（5-FU）, an anticancer chemotherapy drug, was used as a model drug to evaluate the efficiency of the new drug delivery carrier. The loading efficiency of 5-FU was（4.01 0.03）%, and the drug-loaded m PEG-g-CS self-assembled micelle showed a controlled-release effect. In summary, the m PEG-g-CS self-assembled micelle is proved to be a promising carrier with controlled particle size and controlled-release effect. Therefore, it has great potential for the application as 5-FU carriers for effective anti-tumor activity.     

Layer by layer surface engineering of poly (lactide-co-glycolide) nanoparticles: A versatile tool for nanoparticle engineering for targeted drug delivery

Recent work regarding the Layer by Layer (LbL) engineering of poly(lactide-co-glycolide) nanoparticles (PLGA NPs) is reviewed here.The LbL engineering of PLGA NPs is applied as a means of generating advanced drug delivery devices with tailored recognition,protection,cargo and release properties.LbL in combination with covalent chemistry is used to attach PEG and folic acid to control cell uptake and direct it towards cancer cells.LbL coatings composed of chitosan and alginate show low protein interactions and can be used as an alternative to Pegylation.The assembly on top of LbL coatings of lipid layers composed of variable percentages of 1,2-dioleoyl-sn-glycero-3-choline (DOPC) and 1,2-dioleoyl-sn-glycero-3-phosphoL-serine (DOPS) increases NP uptake and directs the NPs towards the endoplasmic reticulum.The antibody anti-TNF-α is encapsulated forming a complex with alginate that is assembled LbL on top of PLGA NPs.The antibody is released in cell culture following first order kinetics.The release kinetics of encapsulated molecules inside PLGA NPs are studied when the PLGA NPs are coated via LbL with different polyelectrolytes.The intracellular release of encapsulated Doxorubicin is studied in the HepG2 cell line by means of Fluorescence Lifetime Imaging.     

ROLE OF Na~+-Ca~(2+) EXCHANGE SYSTEM IN THE PATHOGENESIS OF MYOCARDIAL ISCHEMIA-REPERFUSION DAMAGE

Results from a systematic experiment on isolated perfused rat heart and isolated myc-cytes of adult rat showed that the mechanism of calcium influx during myocardial ischemia-reperfusion is due to the development of intracellular sodium overload during ischemic pe-riod, on reperfusion, the high intracellular Na~+ content activated the reverse direction ofNa~+-Ca~(2+) exchange over myocardial sarcolemma (SL), thus a large quantity of extracellularCa~(2+) fluxed over the SL to the intracellular space, forming a condition of intracellular Ca~(2+)overload, which leads to irreversible damage of the myocardium.     

Histology and antitumor activity study of PTX-loaded micelle,a fluorescent drug delivery system prepared by PEG-TPP

We synthesized PEG-TPP as carrier to encapsulate paclitaxel(PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size(152.1 ±1.2 nm) which is beneficial for enhanced permeability and retention(EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTXloaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles(especially IC50= 0.123 ± 0.035 mmol/L of micelles and 0.298 ± 0.067 mmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.     

In vitro TRANSFORMATION OF RAT ESOPHAGEAL EPITHELIAL CELLS BY FUSARIN C

Fusarin C (FC) is a mutagenic and carcinogenic mycotoxin which was isolated from Fu-sarium moniliforme culture extracts. The Fusarium moniliforme is one of most prevalent fungi found on corn in Linxian, a high risk area for esophageal cancer. This paper reports, for the first time, the malignant transformation of rat esophageal epithelial cells induced by FC. The transformed cells showed several characteristics of transformation. Colonies were formed after seeding these transformed cells either into selective medium free of epidermal growth factor (EGF) and serum, or on semi-solid agar; there was an increase in chromosome number; the expression of c-myc and v-erb-B oncogenes was enhanced in the cells; and squamous cell carcinomas arose after inoculating the cells into nude mice. The results demonstrated transforming effect of FC on rat esophageal epithelial cells, and indicate that the abnormal expression of some oncogenes could serve as a hew property of transformed cells.     

Fabrication and Characterization of Diatomite-supported Activated Carbon Functional Ceramic

Using porous diatomite ceramic as carrier and phenolic resin as carbon precursor, the activated carbon functional ceramic with the activated carbon fixed into porous ceramic was prepared by the impregnation load phenolic resin, carbonization and activation isolated air. The influences of impregnation, curing, carbonization, activation etc. on the material property were discussed. The iodine value, SEM, elemental analyzer, BET and spectrum analysis chart were used to characterize the microstructures and performance of material at different conditions. The results showed that the excellent comprehensive property of activated carbon functional ceramic was gained when it adsorbed phenolic resin in 4 h under vacuum condition at curing temperature of 150 ℃ for 0.5 h and carbonization temperature of 600 ℃ for 1.0 h, and then put into 25wt% KOH for 4.0 h at activation temperature of 700 ℃ for 1.5 h. The iodine value is 176.9 mg/g, the specific surface area can reach 86.3 m2/g and the yield of carbonization is 50.48%.     

Ricinus communis agglutinin I functionalisation of poly(methyl methacrylate) (PMMA) as a substrate for microfluidic device

We report a functionalisation strategy which is able to generate Ricinus communis agglutinin I (RCA 120) modified PMMA microfluidic device for binding and culturing living cells. The functionalisation is achieved by standard amine-aldehyde (Schiff base) reaction through the cross-linker, glutaraldehyde. To prove the ability of the RCA 120 modified PMMA surface, the PC 12 cell line (rat pheochromocytoma cells) has been captured and cultured by the microfluidic device. In the presence of tunicamycin, the dose/time-dependence on decreasing of binding affinity of RCA 120 modified device with PC 12 cell is also observed. The experimental results demonstrate that the lectin-functionalized microfluidic device can be employed as efficient cell culturing platform, and has a great promise of being used as a powerful tool for monitoring the interaction of drug with living cell.     

结合催化气化过程的高效直接碳固体氧化物燃料电池(英文)

This study explores strategies to develop highly efficient direct carbon fuel cells(DCFCs) by com-bining a solid-oxide fuel cell(SOFC) with a catalyst-aided carbon-gasification process. This system employs Cu/CeO 2 composites as both anodic electrodes and carbon additives in a cell of the type: carbon|Cu-CeO 2/YSZ/Ag|air. The study investigates the impact on in situ carbon-gasification and DCFC performance characteristics of catalyst addition and variation in the carrier gas used(inert He versus reactive CO2). The results indicate that cell performance is significantly improved by infusing the catalyst into the carbon feedstock and by employing CO2 as the carrier gas. At 800 ℃, the maxi-mum power output is enhanced by approximately 40% and 230% for carbon/CO2 and car-bon/catalyst/CO2 systems, respectively, compared with that of the carbon/He configuration. The increase observed when employing the catalyst and CO2 as the carrier gas can be primarily at-tributed to the pronounced effect of the catalyst on carbon-gasification through the re-verse-Boudouard reaction, and the subsequent in situ electro-oxidation of CO at the anode three-phase boundary.     

IMMUNOSUPPRESSIVE ACTION OF QINGHAOSU

Qinghaosu (青蒿素), isolated and purified from the Chinese herb Artemisia annua Linn(黄花蒿), and identified as a sesquiterpene with a peroxide bridge and lactone structure,is a highly potent and non-toxic new antimalaria drug. This paper reports the immunosup-pressive action of its water soluble derivative (hemisuccinate Na, QHS). The remarkable sup-pression by QHS of the in vitro ~3HTdR incorporation by mitogen-stimulated mouse spleencells and human peripheral lymphocytes, as well as the spontaneous incorporation by mousethymocytes and blood cells from some leukemia patients is presented and its characteristics aredescribed. The in vivo effect as shown by quantitative PFC is studied and the differencebetween the present in vitro and in vivo effects is investigated. The possible mechanism ofinhibition and discrepancy in effects are discussed.     

可聚合脂质体的研究 Ⅱ．含桐酸脂质体的稳定性和穿透能力的研究

he stability of mixed liposomes containing β-eleostearic acid (β-ESA>and dimyristoylphosphatidylcholine (DMPC) have been studied by measuring therelease of trapped 5(6)-carboxyfluorescein (5(6)-CF) from the inner phase of liposomes. The results showed that the stability of the mixed liposomes decreased withthe increase of the content of β-ESA in liposomes. Addtion of ethanol and TritonX-100 into the liposome suspensions could damage the liposome structure or induceliposome aggregation, followed by the release ofdye;but less release was observed for the polymerized liposomes when thesame amount of ethanol or Triton X-100 were added, which revealed the increase of stability by polymerization.     

Prednisolone succinate-glucosamine conjugate: Synthesis, characterization and in vitro cellular uptake by kidney cell lines

Prednisolone succinate-glucosamine(PSG) conjugate,a prodrug for prednisolone,was synthesized and confirmed by NMR and MS spectrum.The stabilities of the prodrug in PBS(pH 2.50,5.00,7.20,and 7.89) were studied.Cytotoxicity and uptake assay of the prodrug were perfomed on HK-2 and MDCK cell lines.The results showed that compared with prednisolone,the PSG not only did not increase the cytotoxicity but also improved the uptake to 2.2 times of prednisolone by the cells.Thus,it indicated that glucosamine might be a potential carrier for kidney-targeting delivery of prednisolone.     

Mesoporous silica SBA-15 functionalized with phosphonate and amino groups for uranium uptake

Mesoporous silicas have a very attractive ability of sorption and enrichment of metal ions due to their huge surface area and facile functionalization by organic ligands.In this work,phosphonate-amino bifunctionalized mesoporous silica SBA-15(PA-SBA-15) as U(VI) sorbent was fabricated through post-grafting method.The obtained mesoporous silica was characterized by SEM,XRD,NMR and nitrogen sorption/desorption experiments,which revealed the existence of ordered mesoporous structure with uniform pore diameter and large surface area.The adsorptivity of PA-SBA-15 for U(VI) from aqueous solution was investigated using batch sorption technique under different experimental conditions.The preliminary results show that the U(VI) sorption by PA-SBA-15 is very quick with equilibrium time of less than 1 h,and the U(VI) uptake is as large as 373 mg/g at pH 5.5 under 95 ℃.The sorption isotherm has been successfully modeled by the Langmuir isotherm,suggesting a monolayer homogeneous sorption of U(VI) in PA-SBA-15.The sorption is pH-dependent due to the pH-dependent charge of sorbent in the aqueous solution.The thermodynamics research shows that the sorption is a feasible and endothermic process.Based on these results,PA-SBA-15 could be a promising solid phase sorbent for highly-efficient removal of U(VI) ions from waste water and enrichment of U(VI) from a solution at a very low level.