羧基化PEG修饰的磁流体的制备和表征(英文)

制备和表征肿瘤热疗用羧基化PEG修饰的Fe₃O₄磁流体。化学共沉淀方法制备四氧化三铁磁性纳米颗粒,然后用羧基化PEG修饰;用邻二氮菲显色法测定磁流体中铁的含量;沉降方法考察了制备的磁流体的稳定性;通过X射线衍射、透射电子显微镜、红外和振动样品磁强计对制备的磁流体进行表征;测定了磁流体在交变磁场作用下的热效应。羧基化PEG修饰的磁流体稳定性明显优于未修饰的;红外图谱和X衍射图谱证明所制备的磁流体样品由Fe₃O₄组成;透射电镜照片显示磁性粒子分散良好;经X衍射数据计算得磁性粒子的粒径约为5 nm;羧基化PEG修饰磁流体的饱和磁化强度和剩余磁化强度分别为47.01和3.41 emu/g。矫顽力为6.7 Oe;磁流体的特征吸收率为63.0 W/g[Fe]。羧基化PEG修饰的Fe₃O₄磁流体有望用于肿瘤热疗。     

聚乙二醇-6000/Fe_3O_4磁流体的制备及性质研究

目的:制备聚乙二醇(PEG)-6000/Fe3O4磁流体并表征其性质。方法:采用化学共沉淀法制备PEG-6000/Fe3O4磁流体,并用透射电子显微镜、激光粒度测定仪、振动样品磁强计、红外分光光度计等来表征磁流体纳米粒的性质。结果:制得的Fe3O4磁流体表面成功包裹了PEG;平均粒径为(10±6)nm;饱和磁化强度为76.22emu·g-1,顺磁性良好;24h的沉降率为16.8%;纳米粒中铁的含量为69.3%。结论:Fe3O4磁流体经PEG包裹后不但其分散性能得到改善,且磁性保持良好。     

Effect of DMSA-Fe3O4 nano-magnetic fluid-mediated thermotherapy on rabbit VX2 tumor

目的 探讨交变磁场介导的二巯基丁二酸(DMSA)-Fe3O4纳米磁流体热疗治疗兔VX2肿瘤的疗效.方法 建立20只兔后肢VX2软组织肿瘤模型,随机分为4组:A组(对照组)、B组(磁流体局部注射组十热疗)、C组(磁流体动脉灌注组十热疗)、D组(磁流体静脉注射组十热疗),每组5只.成瘤2周后CT测量肿瘤大小.结果 B组和C组的肿瘤中心区[(46.01±1.97)℃和(40.38±1.50)℃]和肿瘤边缘区[(40.35±1.36)℃和(42.57±1.80)℃]的温度显著高于正常肌肉组织[(35.73±1.32)℃和(35.37±1.55)℃]和直肠[(35.69±1.05)℃和(35.25±1.15)℃](P＜0.05);A组及D组肿瘤区域温度无明显增高.治疗后14 d,B组和C组肿瘤生长率分别为(441.04±29.61)％和(354.81±59.51)％,明显低于A组的(1119.90±179.40)％和D组的(1099.90±215.11)％ (P＜0.05).结论 交变磁场介导的DSMA-Fe3O4纳米磁流体热疗能明显抑制兔VX2肿瘤生长.     

DMSA-Fe3O4纳米磁流体介导热疗对兔VX2肿瘤的影响

目的探讨交变磁场介导的二巯基丁二酸(DMSA)-Fe3O4纳米磁流体热疗治疗兔VX2肿瘤的疗效。方法建立20只兔后肢VX2软组织肿瘤模型,随机分为4组:A组(对照组)、B组(磁流体局部注射组+热疗)、C组(磁流体动脉灌注组+热疗)、D组(磁流体静脉注射组+热疗),每组5只。成瘤2周后CT测量肿瘤大小。结果 B组和C组的肿瘤中心区[(46.01±1.97)℃和(40.38±1.50)℃]和肿瘤边缘区[(40.35±1.36)℃和(42.57±1.80)℃]的温度显著高于正常肌肉组织[(35.73±1.32)℃和(35.37±1.55)℃]和直肠[(35.69±1.05)℃和(35.25±1.15)℃](P<0.05);A组及D组肿瘤区域温度无明显增高。治疗后14d,B组和C组肿瘤生长率分别为(441.04±29.61)%和(354.81±59.51)%,明显低于A组的(1119.90±179.40)%和D组的(1099.90±215.11)%(P<0.05)。结论交变磁场介导的DSMA-Fe3O4纳米磁流体热疗能明显抑制兔VX2肿瘤生长。     

壳聚糖-聚丙烯酸磁性微球的制备

目的研究壳聚糖-聚丙烯酸磁性微球的制备及吸附性能。方法在Fe3O4磁流体与分散剂聚乙二醇存在下,壳聚糖与丙烯酸通过戊二醛进行接枝共聚制得表面具有两性基团(-COOH和-NH2)的磁性壳聚糖-聚丙烯酸微球,探讨了聚乙二醇、磁流体、戊二醛交联时间对其制备的影响。结果 20%聚乙二醇量为20mL,0.2g.mL-1磁流体为20mL,25%戊二醛为4mL、反应交联时间为30min。合成的磁性微球粒径约为200nm;磁性微球的饱和磁化强度约为0.5emu.g-1,磁化率可达2.8×10-4;其对胸腺五肽及鸡卵清蛋白有较好的吸附效果,饱和吸附量分别约460mg·g-1和550mg·g-1。结论制备的壳聚糖-聚丙烯酸磁性微球具有较好的吸附性能及磁化强度。     

乳铁蛋白修饰的壳聚糖磁性纳米粒的制备、表征及海马神经细胞摄取

目的制备、表征载四氧化三铁(Fe3O4)的乳铁蛋白修饰的两亲性壳聚糖(Lf-QMC)磁性纳米粒,研究其对海马神经细胞的亲和力及磁场介导下的体内脑靶向性。方法以Lf-QMC纳米粒为基础,采用溶剂挥发法将油酸(OA)改性的磁性Fe3O4(OA-Fe3O4)包载,形成载OA-Fe3O4的Lf-QMC纳米粒,载药量为1.5%;通过傅里叶红外光谱(FTIR)、透射电镜(TEM)、动态光散射(DLS)、X射线衍射(XRD)和振动磁强计(VSM)对其进行表征;刃天青法检测载OA-Fe3O4的Lf-QMC纳米粒对HT-22海马细胞活性的影响;TEM考察该纳米粒被HT-22海马神经细胞摄取的情况;荧光分析法检测载该纳米粒的体内脑靶向性。结果成功构建了载OA-Fe3O4的Lf-QMC纳米粒,其饱和磁化强度为1.2 emu·g-1;该磁性纳米粒在2²00μg·m L-1对HT-22海马细胞无显著毒性;TEM观察显示该磁性纳米粒对HT-22海马细胞有较好的亲和性并能通过有效的途径进入细胞;在磁场的介导下,OA-Fe3O4-Lf-QMC纳米粒可以实现更好的脑靶向效果。结论载OA-Fe3O4的Lf-QMC纳米粒有望在磁场和乳铁蛋白的双重靶向作用下透过血脑屏障向神经细胞递送药物。     

振荡磁场下超顺磁性链霉素PELA微球体外药物释放特征探索

目的制备超顺磁性硫酸链霉素-聚乳酸-聚乙二醇（PELA）微球（superparamagnetic chitosan streptomycin PELA micro-sphercs，spCSPM），研究此微球的特性，并对其在振荡磁场作用下体外药物释放规律进行研究。方法用化学共沉淀法合成纳米超顺磁Fe3O4壳聚糖纳米粒（superparamagnetic chitosan Fe3O4 nanospheres，spFCN），再用双乳化（W／O／W）溶剂蒸发法制备spCSPM。将spCSPM混合人兔血中形成血凝块，在37℃模拟体液中进行体外药物溶出试验，用振荡磁场干预，用酶联免疫法（ELISA）检测硫酸链霉素的释放量。结果振荡磁场能够增加spCSPM血凝块中链霉素释放速率，与非磁性的壳聚糖聚乳酸-聚乙二醇（PELA）微球（chitosail streptomycin PELA microsphercs，CSPM）相比，26d时使药物释放量提高3倍左右。结论spcSPM具有药物缓释功能，振荡磁场可重复性增加体系中药物的溶出，此体系药物缓释周期超过三周。     

动脉粥样硬化靶向性磁共振造影剂的合成及理化特性鉴定

目的 将具有动脉粥样硬化病变靶向性的寡核苷酸适配子与超顺磁性氧化铁颗粒偶联,合成新型靶向性纳米磁共振造影剂。方法 采用壳聚糖共沉淀法包裹Fe3O4;傅里叶变换红外光图谱法判断包裹效果后,与寡核苷酸适配子偶联;聚丙烯酰胺凝胶电泳考察偶联情况;透射电镜法、X射线衍射分析法和MPMS XL-7磁学性质测量法评估其理化性质。结果 壳聚糖包裹形成的超磁性纳米Fe3O4颗粒能高效与寡核苷酸适配子偶联;形成的纳米颗粒粒径为10~20 nm;T2弛豫率为0.284 2×106 mol-1·s-1,质量饱和磁化强度为108 emu·g-1 Fe。结论 超顺磁性氧化铁与具有动脉粥样硬化病变靶向性的适配子偶联,形成的靶向性纳米体系符合磁共振铁造影剂的要求。     

二巯基丁二酸修饰的Fe3O4纳米磁液联合碘油动脉栓塞热疗治疗兔VX2肝癌

目的评估二巯基丁二酸修饰的Fe3O4(DSMA-Fe3O4)纳米磁液联合碘油动脉栓塞热疗治疗兔VX2肝癌的疗效。方法 25只开腹肝左叶种植VX2瘤的实验兔,随机等分为五组:对照组(A组)、碘油栓塞组(B组)、DSMA-Fe3O4纳米磁液+碘油栓塞组(C组)、DSMA-Fe3O4纳米磁液+热疗组(D组)、DSMA-Fe3O4纳米磁液+碘油栓塞+热疗组(E组)。成瘤2周后各组行CT扫描并测量,随后行肝动脉栓塞,D、E组栓塞后诱导热疗。分别在术后7、14d行CT检查,计算肿瘤生长比率、肿瘤增长体积。14dCT扫描结束后每组处死部分实验兔,取完整的肝、肾、脾及肺作病理检查。各组分别在术前1d,术后1、3、7d经兔耳缘静脉采血测ALT和AST。结果所有肝癌模型均建立成功。五组术前肿瘤体积、术前1d、术后7dALT、AST水平均无统计学差异(P>0.05)。术后14d,E组肿瘤体积平均缩小26.7%,而B、C、D三组肿瘤体积分别平均增大了200.7%、209.4%和422.5%。结论 DSMA-Fe3O4纳米磁液联合碘油动脉栓塞热疗兔VX2肝癌有效、安全。     

RGD-tTF水基磁流体的制备及其活性研究

目的探讨RGD-tTF水基磁流体通过磁场和RGD多肽在体外对内皮细胞双靶向的功能。方法通过化学沉淀法以柠檬酸钠为表面活性剂制备水基磁流体(MnFe2O4),弱酸改性后与重组的RGD-tTF融合蛋白结合,利用H-600透射电镜观测纳米粒径,以SUQID鉴定磁性,用MTT法、因子X活化检测和流式细胞仪检测RGD-tTF磁流体生物活性。结果成功制备出的水基磁流体能在磷酸盐缓冲液中稳定分布且具有生物兼容性,实验表明RGD-tTF与水基磁流体结合后对RGD和tTF生物活性均无显著影响,并证实在磁场的作用下能实现了水基磁流体对RGD-tTF的定位作用。结论一种具有内皮细胞双靶向功能的RGD-tTF水基磁流体已制备成功。     

Preparation and characterization of superparamagnetic iron oxide nanoparticles stabilized by alginate

SPION with appropriate surface chemistry have been widely used experimentally for numerous in vivo applications. In this study, SPION stabilized by alginate (SPION-alginate) were prepared by a modified coprecipitation method. The structure, size, morphology, magnetic property and relaxivity of the SPION-alginate were characterized systematically by means of XRD, TEM, ESEM, AFM, DLS, SQUID magnetometer and MRI, respectively, and the interaction between alginate and iron oxide (Fe(3)O(4)) was characterized by FT-IR and AFM. The results revealed that typical iron oxide nanoparticles were Fe(3)O(4) with a core diameter of 5-10 nm and SPION-alginate had a hydrodynamic diameter of 193.8-483.2 nm. From the magnetization curve, the Ms of a suspension of SPION-alginate was 40 emu/g, corresponding to 73% of that of solid SPION-alginate. This high Ms may be due to the binding of Fe(3)O(4) nanoparticles to alginate macromolecule strands as visually confirmed by AFM. SPION-alginate of several hundred nanometers was stable in size for 12 months at 4 degrees C. Moreover, T1 relaxivity and T2 relaxivity of SPION-alginate in saline (1.5 T, 20 degrees C) were 7.86+/-0.20 s(-1) mM(-1) and 281.2+/-26.4 s(-1) mM(-1), respectively.     

热熔挤出技术制备吲哚美辛速释胶囊

目的以热熔挤出技术制备吲哚美辛速释胶囊。方法选用不同的亲水性载体，如聚乙二醇（PEG-6000，PEG-10000）、聚乙烯吡咯烷酮（PVP—k30）、泊洛沙姆188（F-68），应用热熔挤出技术制备吲哚美辛速释胶囊，比较其与物理混合物胶囊及原料药胶囊的药物溶出速率。结果与相应的物理混合物胶囊及原料药胶囊相比，用热熔挤出技术制备的速释胶囊吲哚美辛的溶出速率快，且以PEG-10000／PVP—k30／F-68／吲哚美辛质量比：1：1：1：1系统的药物溶出速率最快。结论用热熔挤出技术制备的吲哚美辛速释胶囊可提高药物的溶出度。     

Novel superparamagnetic iron oxide nanoparticles for tumor embolization application: preparation, characterization and double targeting

The goal of this study was to develop novel embolic nanoparticles for targeted tumor therapy with dual targeting: magnetic field-guided and peptide-directed targeting. The embolic nanoparticles SP5.2/tTF-OCMCs-SPIO-NPs were prepared by surface-modifying of superparamagnetic iron oxide nanoparticles (SPIO-NPs) with o-carboxymethylchitosans (OCMCs) and SP5.2/tTF (SP5.2: a peptide binding to VEGFR-1; tTF: truncated tissue factor) to improve their stability and to target over-expressing VEGFR-1 cells. The physicochemical characterization results showed that the OCMCs-SPIO-NPs have a spherical or ellipsoidal morphology with an average diameter of 10-20 nm. And they possess magnetism with a saturation magnetization of 66.1 emu/g, negligible coercivity and remanence at room temperature. In addition, the confocal microscopy, Prussian blue staining and FX activation analysis respectively demonstrated the peptide-directed targeting, magnetic field-guided targeted and blood coagulation activity of the SP5.2/tTF-OCMCs-SPIO-NPs. These properties separately belong to SP5.2, Fe(3)O(4) and tTF moieties of the SP5.2/tTF-OCMCs-SPIO-NPs. Thus these SP5.2/tTF-OCMCs-SPIO-NPs with double-targeting function should have a potential application in embolization therapy of tumor blood vessels.     

磁性纳米粒在抗肿瘤药物中的应用

磁性纳米粒是一种新兴的正在迅速发展的新型材料,主要为铁氧体(γ-Fe2O3及Fe3O4)。由于其无毒无害,良好的生物相容性,目前在药物控制释放、肿瘤热疗以及智能开关等多个领域备受关注。本文结合近年来国内外对磁性纳米粒的研究报道,主要介绍了磁性纳米粒的性质及其在肿瘤药物缓控释中的应用等。希望能为其以后的研究和应用提供理论依据。     

Combinatorial pulsed laser deposition of Fe, Cr, Mn, and Ni-substituted SrTiO3 films on Si substrates

Combinatorial pulsed laser deposition (CPLD) using two targets was used to produce a range of transition metal-substituted perovskite-structured Sr(Ti(1-x)M(x))O(3-δ) films on buffered silicon substrates, where M = Fe, Cr, Ni and Mn and x = 0.05-0.5. CPLD produced samples whose composition vs distance fitted a linear combination of the compositions of the two targets. Sr(Ti(1-x)Fe(x))O(3-δ) films produced from a pair of perovskite targets (SrTiO(3) and SrFeO(3) or SrTiO(3) and SrTi0(0.575)Fe(0.425)O(3)) had properties similar to those of films produced from single targets, showing a single phase microstructure, a saturation magnetization of 0.5 μ(B)/Fe, and a strong out-of-plane magnetoelastic anisotropy at room temperature. Films produced from an SrTiO(3) and a metal oxide target consisted of majority perovskite phases with additional metal oxide (or metal in the case of Ni) phases. Films made from SrTiO(3) and Fe(2)O(3) targets retained the high magnetic anisotropy of Sr(Ti(1-x)Fe(x))O(3-δ), but had a much higher saturation magnetization than single-target films, reaching for example an out-of-plane coercivity of >2 kOe and a saturation magnetization of 125 emu/cm(3) at 24%Fe. This was attributed to the presence of maghemite or magnetite exchange-coupled to the Sr(Ti(1-x)Fe(x))O(3-δ). Films of Sr(Ti(1-x)Cr(x))O(3-δ) and Sr(Ti(1-x)Mn(x))O(3-δ) showed no room temperature ferromagnetism, but Sr(Ti(1-x)Ni(x))O(3-δ) did show a high anisotropy and magnetization attributed mainly to the perovskite phase. Combinatorial synthesis is shown to be an efficient process for enabling evaluation of the properties of epitaxial substituted perovskite films as well as multiphase films which have potential for a wide range of electronic, magnetic, optical, and catalytic applications.     

丹酚酸膜缓控释滴丸的制备及其体外释放度

目的研究丹酚酸缓释滴丸的制备方法。方法通过固体分散技术,以聚乙二醇6000(polyeth-ylene-glycol 6000,PEG-6000)和聚乙二醇400(polyethylene-glycol 400,PEG-400)为滴丸基质制备滴丸丸心,以乙基纤维素(ethyl cellulose,EC)、丙烯酸树脂高渗(eudragit RL100)、丙烯树脂低渗(eud-ragit RS100)、邻苯二甲酸二乙酯(diethyl phthalate,DEP)为包衣材料,体积分数为95%的乙醇溶液为包衣溶剂进行包衣,利用均匀设计优化处方,制得具有良好缓释效果丹酚酸缓释滴丸。结果以PEG-6000和PEG-400为固体分散辅料可制得外观圆整,质地均匀的丹酚酸滴丸,包衣处方中以乙基纤维素3.0 g、丙烯酸树脂RL100和RS100 1.0 g、邻苯二甲酸二乙酯2.5 mL、体积分数为95%的乙醇溶液100 mL、包衣增质量分数为3%能达到最佳的释放效果。结论所制备的丹酚酸缓释滴丸具有良好的释放效果。