磁性阿霉素纳米微球的制备及在高频磁场中的发热研究

制备一种在高频磁场中能感应发热的用于治疗肿瘤的阿霉素纳米微球，研究其在磁场中的热效应。用超声搅拌冷冻干燥的方法制备药物微球，平均粒径200nm左右。电镜观察其形态为球囊状。将其置于不同介质中于高频磁场中测其温度变化值，实验表明该微球在交变磁场中使介质升温。升温速度与平稳时的温度和微球的量及磁场强度成正比，介质流动性好，升温快。     

Fe3O4磁性微粒的制备及表征

背景：磁性微粒作为一种磁性载体在固定化酶、免疫检测、靶向载药治疗及细胞分离等生物医学领域得到了广泛的应用。目的：制备分散稳定性好,相对磁性强的纳米级Fe₃O₄微粒。方法：以氯化亚铁、氯化铁、氢氧化钠为主要原料,采用化学共沉淀法合成Fe₃O₄磁性粒子。结果与结论：用正交设计法优化了Fe₃O₄微粒的合成工艺条件,得到制备Fe₃O₄粒子的最佳实验条件为Fe²⁺/Fe³⁺的物质的量之比为2∶1、共沉淀时的pH值为11、熟化温度为90 ℃、表面活性剂聚乙二醇的用量为40 mL,此时制得的Fe₃O₄粒子粒径最小,为78 nm,Fe₃O₄溶液的分散稳定性最好,相对磁性最强。从Fe₃O₄的扫描电镜图可以看出,Fe₃O₄微粒晶体颗粒为纳米级。     

磁性阿霉素纳米微球在磁场中磁感应的发热研究

目的：制备一种在高频磁场中能感应发热的用于治疗肿瘤的阿霉素纳米微球，研究其在磁场中的热效应。材料与方法：用超声搅拌冷冻干燥的方法制备药物微球，电镜观察其形态及粒径估测。将其置于不同介质中于高频磁场中测其温度变化值。结果：磁性阿霉素微球为球囊状，平均粒径200nm左右，最小为150nm，最大为350nm，该微球在交变磁场中使介质升温。升温速度与平稳时的温度和微球的量，磁场强度成正比，介质流动性好，升温快。结论：可通过调节磁场强度和磁性阿霉素微球的量使周围温度达到所需值。     

阿霉素磁性壳聚糖微球的制备及释放实验

应用改进的悬浮交联技术制备磁性壳聚糖(chitosan,CS)纳米微球。结果显示:该药物微球基本呈球形,其粒径在200~800 nm之间,并且显示了好的磁响应性。阿霉素(doxorubicin,DOX)为试验药物,DOX和CS以化学键(-N=C-)结合在一起,药物含量在1%~15%(w/w)。pH值的大小对其药物体外释放试验的影响很大,当pH为1、2和4时,7 d内药物的释放从22.0%、13.4%降至4.1%。该微球为pH敏感的磁靶向药物微球。     

rhIL-2与阿霉素白蛋白磁微球靶向治疗肿瘤的协同作用

目的：观察重组人白细胞介素-2(rhIL-2)瘤内注射和阿霉素白蛋白磁微球(ADM-MAM)联合外磁场联合治疗H22荷瘤小鼠的协同作用，并探讨其抗肿瘤作用机制。方法：以荷瘤小鼠的瘤重为指标，观察药物的抗肿瘤活性。以乳酸脱氢酶释放法测NK细胞的杀伤活性。以MTT比色法测淋巴细胞的转化率。以流式细胞术检测肿瘤细胞的凋亡及p53、Fas和FasL的表达。用RT—PCR法测定IL—2及IL—12的表达。探讨抗肿瘤机制。结果：ADM—MAM靶向治疗与rhIL—2联用，可显著减小荷瘤小鼠的瘤重；提高NK细胞的杀伤活性和脾脏淋巴细胞的转化率；减小肿瘤细胞的增殖指数，上调肿瘤细胞p53、Fas和FasL的表达，以及增加脾脏淋巴细胞上IL—2及IL—12的表达。结论：ADM—MAM联合外磁场，具有显著增强抑瘤的作用。rhIL—2能增强ADM—MAM靶向治疗的抗肿瘤作用，其抗肿瘤协同作用主要是通过促进T细胞增殖，刺激NK细胞增长等提高机体的免疫功能而实现的。     

偶联剂修饰纳米磁性微球的制备及其表征

以三氯化铁水溶液作原料,采用部分还原沉淀法,通过控制一些影响反应的参数,制备纳米磁性微球(Magnetic nanoparticles,MNPs),并用道康宁Z-6040硅烷偶联剂对其进行了表面修饰.利用透射电镜、X-射线衍射、红外光谱、古埃磁天平、可见光分光光度计等手段对MNPs的形貌、粒度分布、物相组成、表面包覆官能团、磁化率、分散性等进行了表征.用硅烷偶联修饰前后粒度分布呈高斯正态分布,主要集中在10～25 mm;主要物相为Fe3O4晶体,另外还夹杂着少量γ-Fe2O3;分散性得到改善的同时,磁响应性保持良好.     

磁靶向定位灌注化疗膀胱癌磁性吡柔比星纳米粒的制备与评价

目的构建一种新型的磁靶向定位灌注化疗膀胱癌的吡柔比星纳米制剂,并探讨其磁靶向定位及抗膀胱癌细胞特性,为定位灌注化疗膀胱癌的临床应用提供帮助。方法通过N-N'-羰基二咪唑(CDI)交联剂将治疗膀胱癌的临床药物吡柔比星(pirarubicin,THP)连接在表面氨基化的四氧化三铁(Fe3O4)磁性纳米粒上,制备具有磁性的THP纳米制剂,并在体外考察其磁定位性能和对膀胱癌细胞的抑制作用。结果 THP成功地连接到了粒径40 nm左右的Fe3O4磁性纳米粒上,磁性药物制剂在不同p H值的缓冲液中药物在90%以上,并可在外界磁场作用下定位于靶向部位。对膀胱癌细胞可造成THP和Fe3O4双重抑制效果,抑制率高达58.44%。结论该纳米制剂可通过外界磁场定位于靶向部位,膀胱癌细胞抑制效果明显,为临床定位灌注化疗的应用奠定了基础。     

纳米免疫磁性微球的制备和性能研究

目的:初步探讨纳米免疫磁性微球（Immunomagneticbeads,IMB）的制备方法及其性能。方法:用FeC纳米磁粉为内核,用反相乳液法制备壳聚糖磁性复合微球,用戊二醛活化复合微球并交联鼠抗人CD3单克隆抗体,制备出人CD3纳米免疫磁性微球,用人CD3纳米磁性免疫微球富集人外周血中CD3+细胞,并检测富集细胞的效果。结果:壳聚糖磁性复合微球平均粒径为560nm,粒径分布在409～710nm之间,用此微球制备的人CD3免疫磁性微球蛋白联接率达93.8%,流式细胞术检测人CD3纳米免疫磁性微球分离CD3+细胞纯度达到94.8%。结论:制备的人CD3纳米免疫磁性微球具有分离细胞纯度高,细胞损伤小,不用解离磁球即可检测等特点。     

免疫磁性海藻酸钠载药纳米微球的制备与评价

靶向治疗系统是目前研究的热点,用微乳化-离子交联方法制备包覆阿霉素的碳包铁/海藻酸钠复合纳米微球,以水溶性碳二亚胺为交联剂,将载药微球与单抗Hab18连接,制备出了免疫磁性药物纳米微球.对该免疫磁性微球的理化性能进行了表征,同时检测了免疫磁性微球中抗体的活性和免疫磁性微球与靶细胞的体外结合情况,结果表明,免疫磁性药物纳米微球平均粒径约为171.2nm,外观为球型,铁含量为14.6%,载药量为10.8%,且具有强磁响应性和长时间药物缓释效果.同时在体外该微球能够与靶细胞特异性结合.这种免疫磁性药物纳米微球有望成为一种优良的靶向肿瘤药物载体.     

Fe-Fe3O4核壳结构纳米材料的制备与表征

目的通过还原－氧化方法使作为前躯体的Fe3O4纳米颗粒具有Fe－Fe3O4核壳结构,以作为磁靶向药物载体。方法在管式炉中以H2还原Fe3O4纳米颗粒后,利用压差作用下进入的少量空气缓慢氧化还原后物质,以制备符合预期要求的Fe－Fe3O4核壳结构纳米粒子,并分析产物的X射线衍射（X-ray diffraction,XRD）、透射电子显微镜（transmission electron microscopy,TEM）和振动样品磁强计（vibrating sample magnetometer,VSM）表征结果。结果通过还原-氧化法制备的Fe-Fe3O4核壳结构纳米粒子,形状近似球形,粒径主要分布在60-100nm,比饱和磁化强度达108emu／g,比Fe3O4纳米颗粒高30emu／g,且稳定性良好。结论还原-氧化法制备的Fe-Fe3O4核壳结构纳米颗粒比前躯体磁性强,并具有较高的化学稳定性和生物相容性。     

超顺磁性Fe2O3与Fe3O4用于磁共振胃肠造影剂的粒度比较

目的探讨应用超顺磁性Fe2O3与Fe3O4制备磁共振造影剂的可能性。方法根据超顺磁性理论推导出两种微粒显示超顺磁现象的临界尺寸理论值。根据磁学理论,分析了磁共振造影剂稳定的机理,推导出在磁共振磁场中,两者在造影剂中稳定悬浮的极限尺寸。结果超顺磁性Fe2O3与Fe3O4显示超顺磁现象的临界尺寸理论值分别为24．8nm和31．6nm,在1．5T磁共振磁场中的临界值为7．1nm和11．1nm;在造影剂中稳定悬浮的极限尺寸为13．3nm和14nm。结论超顺磁性Fe2O3与Fe3O4在造影剂中,既能稳定悬浮又具有超顺磁性的临界尺寸为7．1nm、11．1nm。     

The Preparation and Biocompatibility Study on Fe2O3 Magnetic Nanoparticles Used in Tumor Hyperthermia

Objective：To evaluate the in vitro and in vivo toxicity of self-prepared nanosized Fe2O3, which has the potential implication in tumor hyperthermia. Methods： Fe2O3 nanoparticles were prepared by improving co-precipitation, which characterization was detected by TEM, XRD, CMIAS, EDS. MTT assay was used to evaluate the in vitro cytotoxicity test; hemolytic test was carried out to estimate whether it has blood toxicity; Fe2O3 suspended in sterile 0.9% NaCl was intraperitoneally injected into Kumning mouse to calculate the LD50 ; micronucleus （MN） were reckoned to identify whether it is genotoxic. Results：The nanoparticles are brown spherical particles with diameter ranging from 8 to 15 nm, which have good decentralization and stability. The experiments also showed that the toxicity of the material on mouse fibroblast （L-929） cell lines was 0 - 1 degree ; it has no hemolysis activity; LD50 arrived at 5.45 g/kg^-1 after intraperitoneal injection of 1 ml suspension; micronucleus test showed that it has no genotoxic effects either. Conclusion： The results showed that the Fe2O3 nanoparticles are prepared successfully, the self-prepared nanosized Fe2O3 is a kind of high biocompatibility materials and perhaps it is suitable for further application in tumor hyperthermia.     

新型MRI/CT双模态造影剂Au/Fe_3O_4复合纳米团簇制备及表征

目的制备一种新型的MRI/CT双模态Au/Fe3O4复合纳米团簇造影剂,并对其相关性能进行研究。方法利用高温有机热分解法制备粒径可控且分散性良好的Au、Fe3O4纳米颗粒并合成两亲性聚乙二醇-聚乳酸（mPEG-PLA）嵌段共聚物。通过组装的方法以mPEG-PLA为纽带,将Au和Fe3O4纳米颗粒组装为复合纳米团簇。并利用透射电子显微镜（TEM）、X射线能谱仪（EDS）和动态光散射（DLS）分别对所制备纳米团簇的形貌、组成、尺寸及稳定性进行表征。研究不同的组装条件对纳米颗粒的包覆效率（EE）、装载能力（LC）及相应的MRI和CT成像效果的影响。结果制备的Au、Fe3O4纳米颗粒呈球形,分散性、均一性良好,平均粒径分别为7.25nm、9.00nm。两亲性聚合物mPEG-PLA相对分子质量约为11000。为了优化复合纳米团簇的EE和LC及磁学特性,制备Au、Fe3O4纳米颗粒不同配比的纳米团簇。随着Au纳米颗粒比重的增加,mPEG-PLA对纳米颗粒的EE和LC呈现先增加后降低又增加的趋势。通过对其横向弛豫率测量证明,该造影剂缩短T2时间效果明显,并随着Fe3O4纳米颗粒比重的提高,横向弛豫率呈现升高趋势。MRI研究证明,MRI信号强度的改变随Fe3O4纳米颗粒比重的提高而增强。而micro-CT成像研究则表明,随Au纳米颗粒比重的提高,成像效果越明显。结论利用该方法制备出的造影剂粒径可控,稳定性良好,具备良好的MRI/CT造影性质,具有潜在的临床使用价值。     

Synthesis,characterization, biodegradation,and drug delivery application of biodegradable lactic/ glycolic acid oligomers: I. Synthesis and characterization

A series of oligomers or low molecular weight polymers of lactic and/or glycolic acid has been synthesized with different molar ratios of lactic to glycolic acid. These oligomers have been characterized with respect to oligomer composition, molecular weight, intrinsic viscosity, crystallinity, melting temperature, and glass transition temperature. The polymerization conditions for the lactic/glycolic acid oligomer syntheses were as follows: 180-220°C, 5 mm Hg, 5 h, and 0.1 wt% of catalyst (antimony oxide) concentration. The polymeric compositions correlated to the feed ratios of lactic to glycolic acid. The molecular weight of the oligomers ranged from 895.8 ±48.7 to 1368.0 ± 0 D with the intrinsic viscosity ranging from 0.0513 to 0.0814 dl g^-1. The lactic/glycolic acid oligomers were found to be amorphous. The glass transition temperatures of the lactic/glycolic acid oligomers were lower than physiological temperature.     

人干扰素调节因子3基因启动子的初步鉴定

子活性分析表明,IRF3启动子区域定位于主要转录起始位点区域前111-167 bp的区域内.采用转录因子结合位点预测分析软件分析表明,该区域内存在E2F转录因子结合位点.结论 -167～-111 bp区存在IRF3启动子的核心调控元件,转录因子E2F可能参与IRF3的转录调控.     

In Vitro and In Vivo Characterization of MEMS Microneedles

Transdermal drug delivery TDD systems have many advantages but are conventionally limited by the low permeability of skin. The idea of using microneedles to painlessly penetrate the topmost impermeable stratum corneum has previously been put forward. In this paper, the fabrication of solid and hollow silicon microneedles with straight side-walls and with the following dimensions: 20–100 m in diameter and 100–150 m in length is described. In vitro tests demonstrate that with prior solid microneedle application, transdermal drug transport is significantly increased by 10–20 times, with the degree of enhancement being related to needle diameter. In vivo tests in diabetic animals, however, were unable to demonstrate any delivery of insulin through the hollow microneedles. It is proposed that two factors, microneedle length and tip sharpness, have to be improved for systemic drug delivery to be seen in vivo.     

Synthesis and characterization of self-catalyzed poly(ortho-esters) based on decanediol and decanediol-lactate

The synthesis of poly(ortho-esters) (POEs) containing lactic acid dimers in the polymer backbone for possible use in controlled drug release applications is described. These autocatalyzed POEs are prepared by the acid catalyzed condensation of 3,9-diethylidene-2,4,8,10-tetraoxaspiro(5,5)undecane with diols to produce linear polymers. The diols used were a mixture of decanediol-lactate and decanediol in various molar ratio to produce polymers with different lactic acid contents. Polymer structures were confirmed by ¹³C NMR, ¹H NMR, and FT-IR and physico-chemical properties, such as molecular weights, glass transition temperatures and viscoelastic behavior, were also determined.