Redox-responsive molecular gels based on camptothecin prodrug with disulfide linkage for controlled and sustained drug release

A novel camptothecin (CPT) prodrug was successfully synthesized by conjugating CPT to adamantanecarboxylic acid (AD) via a cleavable disulfide linkage. The resulting CPT-ss-AD prodrug could act as a low molecular weight gelator to form molecular gels in water/water-miscible organic solvent mixture. Meanwhile, biodegradable amphiphilic block copolymer mPEG-b-P (MAC-co-DTC) (PPMD) was also employed as an organic framework together with CPT-ss-AD to form gel structure. CPT-ss-AD/PPMD gel exhibited less compact molecular arrangement but much more stability than CPT-ss-AD gel. The two kinds of gels could effectively release the original CPT under reductive condition at a near-constant rate without any initial burst. As compared to CPT-ss-AD single-component gel, the two-component gel, CPT-ss-AD/PPMD, had a significantly higher release rate of CPT, while 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assays also indicated highly potent cytotoxic activity against HeLa cells.     

Preparation and Characterization of Nimodipine-loaded Methoxy Poly （ethylene glycol） -poly （lactic acid） Diblock Copolymer Nanoparticles

Amphiphilic diblock copolymers, methoxy poly （ ethylene glycol）-poly（lactic acid） （MePEG-PLA）, were synthesized from monomers of DL-lactide and methoxy poly （ethylene glycol） by a ring opening bulk polymerizatiou in the presence of stannous octoate. Their chemical structure and physical properties were investigated using FTIR, NMR, GPC, and fluorescence spectroscopy. To estimate the feasibility as colloidal drug carrier, nimodipine （ND） was loaded into MePEG-PLA block copolymer nanoparticles by phaseseparation/dialysis method. The mean diameter and drug loading efficiency of ND-loaded MePEG-PLA copolymer nanoparticles depended ou PLA/MePEG block composition of the copolymer and drug/polymer feed ratio in preparatiou. NMR study confirmed that nimodipine was entrapped into the hydrophobic inner core of MePEG-PLA copolymer nanoparticles and hydrophilic PEG chains were located ou the surface of the drug-loaded polymer nanoparticles. In vitro release experiments exhibited the sustained release behavior of nimodipine from MePEG-PLA copolymer nanoparticles, without any burst effect.     

活性污泥性质对基因工程菌吸附影响研究

基因工程菌在活性污泥中的生存状况是决定其生物强化作用的关键因素,活性污泥吸附对基因工程菌生存状况具有重要影响。在典型活性污泥中,考察了吸附于活性污泥的基因工程菌生存状况,以及活性污泥性质对其基因工程菌吸附能力的影响。结果表明,基因工程菌吸附于污泥絮体后,更有利于其生存。污泥质量浓度增大,吸附能力减小;污泥粒径减小,吸附能力增加;污泥EPS含量越高,吸附能力越强。同时,在相同污泥质量浓度下,普通活性污泥吸附能力大于MBR污泥,表明污泥有机质含量比污泥粒径对基因工程菌吸附的影响更显著。在接种密度为105～1014CFU/mL时,普通活性污泥和MBR污泥对基因工程菌的吸附基本符合Freundlich等温吸附方程。     

Fabrication of PLGA coated silica nanorattle for controlling the drug release behavior

Silica nanorattle with hollow and mesoporous structure has been proven to be an excellent drug carrier.However,how to control the drug release from silica nanorattle is still a challenge.In this study,we designed two methods,in-situ polymerization method and water in oil in water(W/O/W) double emulsion method,to coat a nanosized poly(lactic-co-glycolic acid)(PLGA) layer onto the surface of silica nanorattle for controlling the drug release behavior.Hydrophobic antitumor drug docetaxel was loaded into the PLGA coated silica nanorattle(PLGA@SN).The drug release profile,cellular uptake and cytotoxicity on human liver cancer HepG2 cells were evaluated to prove that the PLGA layer plays an effective role in tuning the drug delivery.     

功能化修饰纳米纤维素的结肠靶向给药载体

 纳米纤维素（cellulose nanocrystals,CNCs）具有优异的生物理化性能,可作为一种理想的新型药物载体。以马来酸酐酯化纳米纤维素（MA-CNCs）为载体,通过酯化反应进一步引入氨基酸连接臂,再与妥舒沙星（TFLX）偶联,得到新型妥舒沙星-氨基酸-马来酸酐酯化纳米纤维素药物轭合物（TFLX-A-MA-CNCs）。采用傅里叶变换红外光谱仪（FTIR）表征技术验证了妥舒沙星与马来酸酐酯化纤维素成功偶联。场发射扫描电镜（FE-SEM）观察发现MA-CNCs 可以较好地包覆药物。对TFLX-A-MACNCs药物轭合物在模拟胃液、小肠液和结肠液中的释药行为进行分析,结果表明MA-CNCs 载体对药物具有良好的包载性,且可实现结肠靶向释药。     

Preparation and Characterization of pH-Sensitive Polyvinyl Alcohol Hydrogel for Cancer Therapy

Hydrogel has emerged as an excellent carrier platform for smart drug delivery and effective cancer treatment due to its high water content, good biocompatibility and sufficient mechanical properties. In this work,the DOX-loaded polyvinyl alcohol（ PVA）hydrogel was prepared by freeze-thawing technique. The swelling test and the mechanical properties of the pure PVA hydrogels were performed. In addition, the in vitro drug release profiles were examined and the in vitro antitumor efficiency against He La cells was also estimated. The results indicated that the resulting PVA hydrogels contained significant amounts of water and possessed good mechanical properties,and DOX-loaded PVA hydrogel exhibited a sustained and p H-responsive DOX release. The MTT assays also demonstrated that the released DOX could effectively inhibit the proliferation of He La cells. Thus,the cross-linked PVA hydrogel can be further developed as a promising platform for cancer therapy.     

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。     

复乳法及其改良法制备的干扰素PLGA微球载药释药特性的对比

改良法在复乳法基础上结合了海藻酸钠与Ca2+螯合形成缓释凝胶的原理。分别用上述两法制备蛋白药物干扰素α-1b的聚乳酸聚乙醇酸(PLGA)微球,以包封率、载药量等为指标,评价其理化性质;扫描电镜观察微球内外形态,软件计算其结构参数;用表面蛋白染色、激光共聚焦显微镜观察蛋白在微球表面及骨架内的分布情况;考察微球体外释药行为。与复乳法相比,改良法所得微球有较高的包封率和载药量(61.85%,0.724 3%),表面孔洞少、孔隙率低;内部孔洞大而少,孔隙率无显著差异;蛋白更多地分布在微球内部孔洞壁上而非表面;突释显著降低,缓释时间延长至20 d以上,30 d累积释药约70%。表明改良法所得微球载药释药性能较好,释药符合缓释制剂标准。     

Frequent mtDNA mutations and its role in gastric carcinogenesis

In order to disclose the relationship between mutations of mitochondrial DNA (mtDNA) and gastric carcinogenesis, we screened the entire mtDNA sequence in 30 cases of human gastric cancer and matched normal tissues by using denaturing high-performance liquid chromatography (DHPLC) and DNA sequencing. Our data showed that high frequency (66.7%, 20/30) of mitochondrial genome mutation occurred in gastric cancer. Among these variants, 17 cases (56.7%, 17/30) were identified to be somatic mutation. High level mutant frequency was found in ND4, ND5 coding genes and D-loop control region, which was 36.7%, 26.7% and 30% respectively. Comparing with complexes Ⅲ, Ⅳ and Ⅴof the electron transport chain, we found that variants appeared to be more frequent in the subunit genes of complexⅠ. Most of mutations were base substitutions (85.4%, 41/48). Our results suggested that mutations of subunit genes encoding complexⅠ, especially ND3, ND4 and ND5 genes, might contribute to human gastric carcinogenesis.     

壳聚糖修饰的Lysozyme-PLGA阳离子纳米药物的制备与表征

通过二环己基碳二亚胺将聚乳酸-羟基乙酸共聚物(PLGA)活化,又与溶菌酶进行化学键合,再采用单乳化-溶剂挥发技术制备表面带正电荷的壳聚糖(CHS)PLGA纳米微球。对纳米微球制备条件进行了优化。结果表明在ρ(CHS)=3 mg/mL,ρ(PLGA)=5 mg/mL,溶菌酶与PLGA的质量比为0.2的条件下,得到的纳米微球包封率为87.8%,载药量为14.7%。微球粒径φ可控制在(450±50)nm之间,在pH=4时,纳米微球表面ζ电位为42.5mV。SEM图像显示经CHS修饰的Lysozyme-PLGA的纳米微球形状规整。药物释放试验显示纳米微球在20 d后释放达到70%,且释放曲线规整。     

二次金汞齐冷原子荧光光谱法测定大气痕量汞

在已有仪器的基础上进行改装,建立了二次金汞齐冷原子荧光光谱法(CVAFS)测定大气中痕量气态元素汞(GEM)和颗粒态总汞(TPM)的方法.该方法的检出限为2 pg,二次金汞齐的转移效率为99%,在0~2 ng范围内做标准曲线,线性关系为0.999 5,检测精密度为1.89%.运用该方法于2009年7月对厦门地区大气环境中的GEM和TPM进行了采集检测,结果显示厦门地区未受明显汞污染.该分析方法也能用于其他环境样品痕量汞的检测.     

黄芪种衣剂对提高黄芪幼苗生化指标的影响

通过对黄芪种子进行种衣剂包衣处理后,考察黄芪种衣剂对黄芪幼苗部分生化指标的影响.将精选的黄芪种子,经变温处理12 h后用吸水纸吸至表面无水,于室温下风干30 min,然后用黄芪种衣剂(AM)和生产中常用的ND牌种衣剂(ND)进行包衣,AM所用剂量分别为种子干质量的2%、4%、6%和8%,ND所用剂量为种子干质量的8%,并依次标记为AM(2%)、AM(4%)、AM(6%)、AM(8%)和ND(8%),空白种子做对照(CK),然后以蛭石为基质,定量装盆,定量浇水,同时将包衣种子和对照种子进行定量播种,并于播种后进行形态指标、脯氨酸含量、MDA含量、POD酶活性、CAT酶活性的测定.黄芪经种衣剂包衣后可以增加脯氨酸含量,保护酶蛋白结构,提高POD和CAT两种保护性酶活性.黄芪种衣剂能够增加黄芪幼苗体内的脯氨酸含量,提高保护性酶酶活性(POD和CAT),正确的使用黄芪种衣剂可以提高黄芪幼苗的抗逆性.     

以吉西他滨为主联合奥沙利铂、替加氟治疗原发性肝癌／胰腺癌疗效观察

目的观察以吉西他滨为主联合奥沙利铂、替加氟治疗原发性肝癌/胰腺癌疗效。方法采用吉西他滨联合奥沙利铂,替加氟组成的化疗方案对13例原发性肝癌/胰腺癌患者进行全身化疗,并对其疗效及毒副反应等进行观察。结果13例患者中,有效率(CR PR)为30.8%(4/13),SD率为30.8%(4/13),CR PR SD率为61.6%(8/13)。9个月生存率分别为61.6%;13例患者中,在前2个周期的化疗后13例患者的CA199、AFP均有不同程度的降低。13例患者均出现血液学毒性,白细胞下降最为明显,表现为Ⅲ～Ⅳ度骨髓抑制。结论吉西他滨联合奥沙利铂,替加氟治疗原发性肝癌/胰腺癌安全有效。     

功能化介孔二氧化硅微球的药物输送行为分析

介孔二氧化硅(MSNs)作为一类新型的药物载体在药物缓控释领域的应用方兴未艾。采用模板诱导和自组装方法合成MCM-41型介孔二氧化硅纳米颗粒,并通过聚乙二醇(PEG)的表面修饰,制备出一类具有高亲水性、高孔隙率、高比表面积的MSNs修饰微球。采用氮吸附(BET)、扫描电镜(SEM)、透射电镜(TEM)、粒径分析等手段表征并对比了聚乙二醇(PEG)修饰前后的MSNs基础理化性能。在此基础上,选用阿霉素作为模型药物,包埋于介孔材料中,对比了PEG修饰前后MSNs中阿霉素的装载量、包封率及释放行为。选用乳腺癌细胞MCF-7为模型癌细胞,选用人血清蛋白(HAS)作为模型蛋白,考察了两种材料对细胞的生物安全性及对蛋白的吸附情况,并将两种材料所对应的载药微球与MCF-7进行共培养,探究两种载药系统对癌细胞的灭杀情况。     

磁流体靶向热疗对小鼠胰腺癌的作用

 为探讨磁流体靶向热疗对小鼠胰腺癌的体外和动物治疗作用,利用前期建株的小鼠胰腺腺泡细胞癌株(MPC-83)分别进行体外热疗和动物实验.对MPC-83 进行水浴热疗,分别调热疗温度为37、42、46、50℃,作用30 min,显微镜观察细胞形态变化,流式细胞仪检测凋亡和坏死细胞百分比.选择4 周龄雌性昆明种小鼠,建立MPC-83 胰腺癌皮下肿瘤模型,观察磁流体热疗(46℃和50℃)对荷瘤小鼠的作用及其病理学变化.流式细胞仪检测46℃和50℃热疗细胞凋亡和坏死百分比分别为46.13%、89.33%,与对照组比较,差异具有统计学意义(P<0.05).热疗后第14 天,46℃和50℃热疗组肿瘤生长率分别为-0.64±0.73和-0.72±0.79,与3 个对照组比较,肿瘤生长受到明显抑制(P<0.05).病理学检查示磁流体对照组,在注射磁流体24 h 可见散在的磁性纳米微粒在一定范围内分布于肿瘤细胞之间,部分肿瘤细胞和吞噬细胞吞噬了磁性纳米微粒.热疗14 d 肿瘤完全消失的小鼠皮下组织未见肿瘤细胞,可见皮下残存磁性纳米微粒,被吞噬细胞吞噬.各对照组小鼠瘤体生长旺盛,细胞核浓染分裂,可见病理性核分裂像.磁流体靶向热疗可以达到杀伤胰腺癌细胞的理想温度,能有效抑制MPC-83 胰腺癌生长,延长小鼠生存期.     

含时波包和准经典轨线法研究H(~2S)+NH→N(~4S)+H_2反应及同位素效应

在Poveda和Varandas构建的4 A″态势能面上,使用含时波包量子方法对反应H(2S)+NH进行了动力学的研究.首先计算了不同振动态和总角动量下该反应的反应概率、积分反应截面.计算中考虑了离心突然近似(centrifugal sudden approximation)和科里奥利耦合(Corioli coupling effect).然后计对同位素反应进行了计算,分析对比该体系的同位素效应,并研究了科里奥利效应在同位素反应中的影响.最后用准经典轨线(QCT)法计算了反应H+ND和D+ND的矢量性质,分析了碰撞能和同位素对反应动力学性质的影响.     

布洛酚-邻氨基苯酚衍生物的合成及酪氨酸酶催化的释放研究

设计并合成了邻氨基酚布洛酚酯,根据推论的酪氨酸酶催化反应机理,进行了模拟实验研究。邻氨基酚布洛酚酯在酪氨酸酶和芳香胺存在下,发生了氧化、加成和取代反应,实现了布洛酚的释放,表明该设计在黑色瘤治疗中的潜在应用前景。     

可降解纳米氧化钇空心球载药体系的体外抗肿瘤效应

纳米氧化钇空心球在生物医学领域具有广泛的应用.以酚醛树脂微球为模板,合成出了尺寸均一、分散性好的纳米Y₂O₃空心球(HYNPs).它不仅在体外表现出显著的酸性降解行为,而且负载抗肿瘤药物阿霉素(DOX)后,载药体系HYNPs-DOX也表现出明显的pH响应药物释放特点.pH为5.0时,72 h的药物释放可达到70.46%;而pH为 7.4时,72 h的药物释放仅25.04%.进一步通过激光共聚焦显微镜监测载药体系在细胞内的DOX释放,发现随着时间的延长,细胞内DOX的荧光逐渐增加,表明DOX在细胞内释放量的增加.体外抗肿瘤细胞毒性结果显示,HYNPs对肿瘤细胞MCF-7和MDA-MB-231的活性没有影响,而HYNPs-DOX则表现出较高的体外抗肿瘤效应,与游离DOX相当.可见,该材料作为抗肿瘤药物载体具有潜在的应用价值.     

胚期接种IBD疫苗对雏鸡ND4倍剂量免疫接种效果之影响

为了研究用IBD疫苗进行鸡胚免疫的可行性，探讨了胚期接种IBD疫苗对雏鸡ND4倍剂量免疫接种效果的影响．将IBD中等毒力疫苗接种18日龄鸡胚，出壳后采用4倍剂量ND疫苗进行免疫，通过抗体水平、免疫细胞数量及功能和免疫保护力等的检测，结果表明：胚期接种IBD中等毒力疫苗对雏鸡4倍剂量免疫仍具有免疫抑制作用．