Dialdehyde starch nanoparticles： Preparation and application in drub carrier

Dialdehyde starch nanoparticles (DASNP) were prepared by the redox reaction of NaIO4 and starch in water-in-oil microemulsion. IR spectrum showed that DASNP had aldehyde groups, and quantitative alkali consumption showed that its dialdehyde content was about (50±5)%. The average diameter of DASNP determined by SEM was about 100 nm. TGA-DTA showed that its thermal stability was better than starch nanoparticle (StNP) and dialdehyde starch (DAS). Its low biological toxicity was detected by cell experiment. Also the best mass ratio of doxorubicin (DOX) to combined DASNP detected by UV-VIS was 15 : 1, and the product was effective for controlled release of DOX. The cell experiment showed that the drug-carrier particle (DOX-DASNP) can release DOX for a long time and strengthened the effect of the anticancer drug. This work demonstrates that the DASNP, which has good thermal stability, small particle size, low biological toxicity, and slowly anticancer drug-releasing to strengthen drug effect, is a potentially useful carrier for anticancer drug.     

叶酸修饰聚酰胺-胺负载5-氟尿嘧啶纳米给药体系的制备及其体外性能研究

使用化学键键合的方式分别将叶酸(FA)和5-氟尿嘧啶-1-基乙酸(FUA)偶联于树状大分子聚酰胺-胺(PAMAM)制备纳米载药体系FA-PAMAM-FUA,并结合单因素分析法筛选出最佳制备条件为FA∶PAMAM∶FUA的物质的量的比为10∶1∶450,p H值为6.用紫外可见光谱、红外光谱和纳米粒度仪对FA-PAMAM-FUA的光学特性、粒径大小和体外释药性能进行了表征.结果表明:优化条件下制备的FAPAMAM-FUA粒径呈正态分布,平均粒径为90.28±20.00 nm,分散度为0.258±0.002(n=3),体系载药量达28.45%,FA-PAMAM-FUA给药体系对药物具有一定的p H敏感特性以及缓释功能.采用MTT法考察了5-Fu、FA-PAMAM-FUA对乳腺癌细胞MCF-7的增殖抑制作用,结果表明两者对MCF-7细胞的增殖具有明显地抑制作用,剂量依赖性强,随浓度的增高,FA-PAMAM-FUA对癌细胞增殖抑制作用较5-Fu明显增强.     

Preparation of folateconjugated starch nanoparticles and its application to tumor-targeted drug delivery vector

The lower toxicity and high effect of drug are very important for clinic therapy. So more and more atten-tion has been paid to the targeted drug delivery system. Folate receptor (FR) has been reported to be vastly overexpressed in most human tumors but se…     

5-氟尿嘧啶壳聚糖纳米微球的制备及表征

壳聚糖(CS)作载体,与三聚磷酸钠(TPP)和5-氟尿嘧啶(5-Fu)发生离子交联反应,制备具有缓释效能的5-氟尿嘧啶壳聚糖纳米微球,并以微球载药量、颗粒大小为指标设计优化了其制备方法,考察不同因数水平对微球的载药量的影响。用傅立叶红外光谱表征了其结构,用激光散射粒径仪测得微球的平均粒径为143~212 nm。氟尿嘧啶壳聚糖微球最大载药量为48.3%,在pH 7.1磷酸盐缓冲溶液中对氟尿嘧啶的缓释作用明显,释放周期较长,药物含量越大,药物从微球中释放出来的速率越快,可作为靶向药物控释体系。     

Labelling of a pyrazole derivative with 131I and investigation of its radiopharmaceutical potential

We investigated the radiolabeling efficiency, in vitro stability, and biodistribution of radioactive iodine (131I)-labeled 4-benzoyl-1-(4-carboxyphenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid (P3CA). A quality-control study of the labeled substance ( 131I-P3CA) was conducted using electrophoresis and radio thin-layer chromatography (RTLC). Biodistribution studies were undertaken in 9 female albino Wistar rats. Rats were killed at various times (15, 60 and 180 min), their organs removed, and percentage of injected dose per gram (ID%/g) values calculated. The labeling yield of P3CA was 97.08%±0.80%. The maximum uptake of 131I-P3CA was seen in the lungs, stomach and spleen at 15 min. The uptake of labeled compound decreased over time in the lungs, whereas that in the stomach decreased. These data suggest that 131I-P3CA had high binding efficiency, high uptake in the lung, and sufficient stability to be used in diagnostic studies.     

PHBV/葡聚糖纳米药物载体的制备及表征

两亲性聚合物纳米颗粒作为疏水性抗肿瘤药物载体因其能够增强化疗效率并降低毒副作用而受到广泛关注.采用双乳液溶剂挥发法制备了聚(3-羟基丁酸酯-co-3-羟基戊酸酯)(PHBV)/葡聚糖纳米颗粒,测得平均粒径为205.0±6.9nm,Zeta电势为-1.59±0.12mV,纳米颗粒具有明显的壳核结构,粒径均一,分散性良好.将疏水性化疗药物顺铂包载后,其粒径及电势均无明显变化,载药量达19.3±2.9%.顺铂在模拟肿瘤细胞环境pH=5.5的磷酸盐缓冲液(PBS)中比正常细胞环境pH=7.4时释放更快,且累计释放周期均长达7d以上,表明该药物载体具有一定的pH响应性以及优异的缓释性能.细胞集落形成实验表明PHBV/葡聚糖纳米药物载体具有良好的生物相容性,而载药纳米颗粒对肿瘤细胞的毒性明显高于正常细胞,表明该纳米颗粒对肿瘤细胞具有更强的杀伤作用.综上所述,PHBV/葡聚糖纳米颗粒具有两亲性分子结构,合适的粒径及Zeta电势,显著的缓释效果,对肿瘤细胞具有pH响应性及更强的杀伤作用等优势,有望成为一种新型纳米药物载体,在癌症化疗中显著提高药物利用率并降低毒副作用.     

壳聚糖-5-氟尿嘧啶高分子前药的合成与表征

为了合成控释型高分子前药,以壳聚糖为载体材料、5-氟尿嘧啶为模型药物,设计并合成了壳聚糖-5-氟尿嘧啶高分子前药,其结构经红外光谱、紫外-可见光谱证明．采用紫外一可见光谱仪,测得其载药率为16．4％．在pH为7．2的磷酸盐缓冲溶液中,1个月的累积释药量约占总含药量的68％,表现出明显的缓释效果．     

Emplacement age and tectonic implications of the Xilinhot A-type granite in Inner Mongolia,China

A new rock type of granite, approximate 45 km^2 in area and located about I0 km south of Xilinhot, Inner Mongolia, was found in the Sunitezuoqi (or called Suzuoqi)-Xilinhot tectonic belt and identified as an A-type miarolitic intrusion. The pluton has miarolitic structure and is composed chiefly of perthite, quartz, euhedral albite and potassium feldspar. Various types of textures occur in the pluton, such as perthitie, graphic and myrmekite textures. Only quartz is found in miarolitic cavity. This A-type granite with seagull-shaped REE patterns and obvious negative Eu anomaly (δEu=0.24--0.28) is high in SiO2 (76%--77%), K and Na (Na2O K2O=7.75%--8.15%) and low in Ca(CaO=0.20%--0.22%), Fe and Mg. Both petrographical observations and chemical compositions indicate that it is an A-type granite. Zircon SHRIMP U-Pb analyses indicate that this A-type granite was emplaced at 276 2 Ma and coeval with the same type of granites in the adjacent areas. Therefore, it suggests that this pluton was likely formed in a post-orogenic extensional setting and probably related to break-off of subducted slabs in Central Asian Orogenic Belt (CAOB), which indicate that the Sunitezuoqi-Xilinhot belt was tectonically evolved into post-orogenic stage since early Permian.     

聚羟基丁酸酯缓释微粒作用下的埋植给药系统

制备了以壳聚糖水凝胶为基质的温度敏感型、可注射、并能够在体内生物降解的新型皮下埋植制剂,考察了该制剂中水溶性小分子药物的体外释放规律。为降低该类药物的释放速度,首先利用溶剂非溶剂法,以生物可降解的聚羟基丁酸酯为骨架,制备了抗癌药物5-氟尿嘧啶的微粒。在优化配比下,微粒收率达90%以上,包封率95%左右;然后将微粒温敏型水凝胶耦合制成复合给药系统。药物微粒化与温敏型水凝胶的耦合有效地控制了药物植入初期的“突释”问题,并将药物的释放周期延长至将近10个月。     

A new drug carrier: Magnetite nanoparticles coated with amphiphilic block copolymer

This paper reports on the synthesis and characterization of 4 nm magnetite nanoparticles coated with amphiphilic block copolymers of poly(ethyl methacrylate)-b-poly(2-hydroxyethyl methacrylate) (PEMA- b-PHEMA) by surface-initiated atom transfer radical polymerization (ATRP), which can act as new po-tential carriers for hydrophobic targeted drug delivery. Vibrating sample magnetometer analysis indi-cated that the magnetite nanoparticles were superparamagnetic at room temperature. Thermogravim-etric analysis (TGA) was applied to studying the property of surface of magnetite nanoparticles, and the surface density of macromolecules was calculated. The grafting density of oleic acid, BrMPA and PEMA was 5.8, 3.9, 0.16 chain/nm2 respectively, which indicates that the initiation efficiency decreases due to the influence of large space of oleic acid molecules. In vitro progesterone and (-)-isoproterenol hy-drochloride release in phosphate buffered saline (PBS) at pH 7.0 and 37℃ was conducted in order to demonstrate the function of drug loading and release. The results showed that the amount of drug carried into the core-shell Fe₃O₄@PEMA-b-PHEMA depends on the length of hydrophobic segment of block copolymer. The release of progesterone (37% after 22 h in our previous work) was compared with the release of (-)-isoproterenol hydrochloride (80% after 50 min), demonstrating that the strong hy-drophobic interaction between hydrophobic segment and drug can effectively control the release of hydrophobic drugs.     

庆大霉素/水杨酸/壳聚糖复方纳米粒的制备及体外释放

通过壳聚糖与三聚磷酸钠的离子交联作用制备了具有拮抗庆大霉素耳毒性功效的庆大霉素/水杨酸复方壳聚糖纳米粒。用紫外分光光度计、纳米粒度仪和Zeta电位仪、透射电子显微镜、扫描电子显微镜、傅里叶变换红外光谱仪和X射线衍射仪等考察了壳聚糖纳米粒的粒径、zeta电位、形态、载药能力及体外释放行为。结果显示复方纳米粒为球形,平均粒径为40 nm;庆大霉素与水杨酸的包封率分别为(91.24±0.24)%和(80.75±0.15)%,载药量分别为(34.15±1.02)%和(38.35±0.48)%;在体外释放试验中,庆     

小檗碱聚乳酸微球的制备工艺及特性研究

采用溶剂挥发法制备小檗碱聚乳酸微球, 选择小檗碱与聚乳酸的投料比、二氯甲烷与水的体积比和乳化剂PVA的质量分数3个因素为实验因素,以包封率和载药量为优化指标, 采用L9(3⁴)正交试验优选最佳处方和制备工艺,测定微球的粒径分布、包封率,并进行体外释药试验。小檗碱聚乳酸微球的算术平均粒径为(53.0±3.5)μm(n=500),载药量为(8.96±0.3)%(n=3),药物包封率为(83.4±0.5)%(n=3),37℃时30d内微球体外累积释药量为82.03%。小檗碱聚乳酸微球球形圆整,释放良好,分子量2.5万左右的聚乳酸较适宜制作微球。     

p-Hydroxybenzoic acid (p-HA) modified polymeric micelles for brain-targeted docetaxel delivery

Chemotherapies for brain diseases have been hampered due to the inability of transport of drug across the blood-brain barrier (BBB). In order to overcome the barrier, p-hydroxybenzoic acid (p-HA), a small molecule of benzamide analogue, was used as a ligand for brain-targeted drug delivery. The p-HA was conjugated to PEG-DSPE to form p-HA-PEG-DSPE. Docetaxel-loaded polymeric micelles were prepared by a thin-film hydration method using methoxy-poly(ethylene glycol)-distearoylphosphatidyl- ethanolamine (mPEG 2000 -DSPE) as a carrier and the p-HA-PEG-DSPE as a brain targeted material. The prepared micelles showed spherical with a mean diameter of (18±3) nm. Encapsulation efficiency and drug loading were (83.49±1.3)%, (7.7±1.2)% for un- modified micelles and (80.65±1.6)%, (7.47±1.8)% for p-HA-modified micelles, respectively. In vitro cellular uptake experiments showed that the p-HA-modified micelles increased BCECs cellular uptake by 1.2 times compared to the unmodified micelles. Ex vivo near-infrared fluorescence imaging showed that brain uptake of the p-HA-modified micelles was 1.3-1.8 times higher than that of the unmodified micelles. In vitro cytotoxicity assay against glioblastoma cell U87 MG showed that inhibition rate of the p-HA-modified micelles increased by 1.2 times compared to that of the unmodified micelles and 1.7 times compared to that of DTX. Survival time of nude mice bearing intracranial glioblastoma showed that the lifetime of saline group, Taxotere group, mPEG-DSPE/DTX micelles group and p-HA-PEG-DSPE/DTX micelles group was 22, 27, 32 and 45.8 d, representively, which indicated that anti-glioblastoma activity of DTX could be significantly enhanced by the p-HA-modified polymeric micelles. These results demonstrated that the p-HA-modified micelles could be a promising brain-targeted drug delivery system for hydrophobic drugs against glioblastoma.     

全反式维甲酸对小鼠胚胎不同阶段神经干细胞诱导作用研究

目的:探讨全反式维甲酸对小鼠胚胎不同阶段神经干细胞(NSCs)的诱导分化情况.方法:分离孕12.5d及15.5d的胚胎小鼠脑皮质.取第3代NSCs,用含1μmol·L-1的全反式维甲酸在体外诱导小鼠胚胎不同阶段的NSCs.诱导5d后,通过神经元微管相关蛋白2(MAP2)免疫荧光染色和Westernblots检测NSCs分化为神经元的比例.结果:与对照组相比,全反式维甲酸可明显提高神经元分化的比例.E12.5干细胞和E15.5胚胎干细胞分化为神经元的比例分别为30%±1.47%和16.21%±1.36%.结论全反式维甲酸具有显著的促神经干细胞分化成神经元的效应,并对胚胎不同阶段神经干细胞的诱导作用有所不同.     

5-氟尿嘧啶类脂囊泡药动学和组织分布研究

用非离子表面活性剂制备5-氟尿嘧啶(5-Fu)囊泡,并对其进行了小鼠体内药动学和组织分布的研究.采用薄膜分散法制备5-Fu的类脂囊泡,以5-Fu水溶液为对照,尾静脉注射自制5-Fu囊泡和5-Fu水溶液,利用高效液相色谱法检测血浆和各组织中的5-Fu浓度,利用统计学方法计算了5-Fu在小鼠体内的药动学参数及小鼠的组织分布参数.与注射水溶液组相比,5-Fu囊泡组MRT值延长,AUC0～t值增加.组织分布结果显示:5-Fu囊泡在肝、肾中AUC值显著增加;5-Fu囊泡明显延长了5-Fu在体内的作用时间,比普通水溶液具有一定的缓释和提高生物利用度的作用.     

Origin and nature of cold seep in northeastern Dongsha area, South China Sea: Evidence from chimney-like seep carbonates

The occurrence of seep carbonates is one of the characteristic features for cold seep sites at continental margins.The carbonates documented the venting history of methane-rich fluid.Compared to the chemoherm carbonates and carbonate pavements which formed on the sediment-water interface,chimney-like seep carbonates precipitated around fluid conduits below the sediment-water interface therefore better recording information of the past fluid flow and composition.Here the chimney-like seep carbonate samples from the northeastern Dongsha area of the South China Sea were studied to understand the origin and nature of the venting fluids and their potential relationship with gas hydrate deposits underneath the seafloor.Based on the occurrence,morphology,petrology,mineralogy and C-and O-isotope compositions,combined with present and past bottom water temperatures and the timing of methane release events,the oxygen isotopic fractionation between calcite and water were used to estimate the equilibriumδ18O values of the precipitating fluids.Theδ13C values ranging from 56.33‰to 42.70‰V-PDB and thus clearly show that the studied chimneys were mainly derived from biogenic methane oxidation.The calculated equilibriumδ18O values of the precipitating fluids ranged from 1.9‰0.3‰to 0.6‰0.3‰V-SMOW,with an average of 1.4‰0.3‰V-SMOW which is heavier than those of seawater even at the last glacial maximum.It is considered that the formation of chimney-like carbonates was closely related to methane hydrate dissociation in the area.The methane hydrates contributed as much as45.7%of water to the venting fluids.It is suggested that the climate and environmental changes(e.g.sea-level lowering,down-cutting canyons and mass wasting)are the major mechanisms maybe responsible for the destabilization of methane hydrates in the study area.The extensive occurrence of seep carbonates indicates that a large amount of the methane released from methane hydrate dissociation has been effectively captured and sequestered by microbial anaerobic oxidation of methane(AOM)before it escapes into the water column.     

Preparation,characterization and antibacterial property of naringin loaded PLGA nanospheres

Naringin is a predominant flavanone in grapefruit and shows a variety of biological effects such as antioxidative, anticancer, anti-inflammatory and antibacterial activity. However, its application in pharmaceutical field is limited by low water solubility, poor bioavailability and instability. To overcome the problem, naringin has been encapsulated in poly(lactic-co-glycolic acid) (PLGA) polymer by emulsion-diffusion-evaporation method in this work. Moreover, naringin loaded PLGA nanospheres were characterized by scanning electron microscope (SEM), dynamic light scatter method (DLS), fourier transform infrared (FTIR) spectra, UV–vis spectra and fluorescence spectra of DNA-EB competition displacement. The mean diameter of PLGA nanospheres and NRG/PLGA nanospheres was 123 ?± ?25 ?nm and 137 ?± ?30 ?nm, respectively. The drug encapsulation efficiency was 86.4% while the drug loading rate was 22.3%. The fluorescence spectra of the competitive DNA-binding experiments revealed that the functional activity of naringin was retained after loaded in PLGA. It is revealed that the initial burst effect happened in the initial 24 ?h and followed by sustained release lasting for 10 days. Moreover, the nanospheres exhibited strong antibacterial activity, and 99.9% of E. coli and S. aureus were killed when treated with naringin loaded PLGA nanospheres at the concentration of 0.2 ?mg ?mL^?1 within 24 ?h. Furthermore, the viable cells remained only 48% when the concentration of NRG/PLGA nanospheres was 32 ?μg ?mL^?1 and NRG/PLGA nanospheres was important for inhibition of cancer cells. It is concluded that the stable naringin loaded PLGA nanospheres could have potential application in food industry and nanomedicine field.     

反相微乳液法制备5-Fu磁性靶向药物及其释药性能

以5-氟脲嘧啶（5-Fu）为模型药,壳聚糖（cs）为包覆材料,纳米四氧化三铁（Fe,O。）作为磁核,戊二醛为交联剂,通过反相微乳液制备5-Fu磁性靶向纳米微粒。最佳实验条件为：乳化剂用量为8％（v／v）,壳聚糖浓度为1．5％（w／w）,Fe3O4／CS为0．6（w／w）,复合乳化剂的HLB值为6,5-Fu／CS为0．4（w／w）,油水体积比为3：1,反应温度为55℃。磁性靶向药物的产率为83．06％、载药率为13．90％、包封率达到56．67％。通过模拟胃液（pH=1．8）和肠液（pH=7．6）做体外药物缓释实验。结果显示,在两种介质中,27小时内药物释放累积释药量分别为11．90％和10．23％,一定程度上达到了缓释、延长药效的目的。     

Identifying paleoflood deposits archived in Zhongba Site, the Three Gorges reservoir region of the Yangtze River, China

Based on the principle that the present is the key to the past, detailed analyses, such as AMS ^14C dating, grain size, component and morphology of heavy minerals, micro-morphology of zircon, Rb/Sr, magnetic susceptibility and total organic carbon （TOC）, were conducted to identify paleoflood sediments archived in Zhongba Site. The results indicate that the plaeoflood sediments bear great similarities with modern flood sediments in the following aspects： （1） probability cumulative curves mainly show a pattern of 3-4 segments; （2） grain-size distribution of suspended matter ranges between 3 and 10（I）; （3） the sediments are well-sorted, most of which are suspended matter （〉50%）; （4） the same species, quantity and morphology of heavy minerals; （5） scanning electronic microscope images show that shapes of zircon are mainly oval and nearly spheral, rounded due to long-distance transport; （6） higher Rb/Sr values （0.55-0.66）than those of sediments from cultural layers （0.03-0.26）; （7） magnetic susceptibility values （133.73-433.05 10^-6m^3/kg） are lower than those of sediments from cultural layers （959.25-2442.44 10^-6 m^3/kg）; （8） TOC （0.14%- 0.33%） are lower than those of sediments from cultural layers （1.13%-2.95%）. Our results demonstrate that, except for the 1981 flood, there are at least six paleoflood events that occurred during the Qing Dynasty, the middle of Song Dynasty, the early Warring States （400BC-350BC）, the West Zhou Dynasty （920BC-900BC）, the Xia Dynasty （2070BC-1600BC）, and the late Neolithic Age （3000BC-2300BC）, respectively.     

吲哚美辛聚氰基丙烯酸正丁酯纳米粒的制备

以生物降解型聚氰基丙烯酸正丁酯为载体材料,采用乳化聚合法制备吲哚美辛纳米粒,通过单因素试验初选、U₅(5³)均匀设计优选制备工艺,用透射显微镜、激光粒度分析仪、紫外分光光度法、X-射线衍射的手段对其特性进行了表征。结果表明,在pH1.5,Dextran-70与Pluronic F-68质量比为4∶1,氰基丙烯酸正丁酯体积分数为0.7%,搅拌速度为800r/min条件下制备的吲哚美辛纳米粒各项指标较为满意。特性研究表明：优化条件下制备的纳米粒球形圆整、无粘连、平均粒径为（127±3）nm,分布均匀,包封率为82.97%,载药量为64mg/g,且吲哚美辛在纳米粒中的无定形程度增加。