氨甲喋呤铁磁性微球的制备及物理性质测定

目的：制备氨甲喋呤铁磁性微球，探讨工艺条件对成球的影响，并测定微球的粒径，磁性物质和药物的含量以及药物释放度等主要物理性质。方法；以人血白蛋白作载体，磁铁粉作磁响应物质用加热固化法制备抗肿瘤药物ＭＴＸ的磁性微球，显微镜下观察微球形态大小，计算粒径分布，重量法测定磁性物质的含量，紫外分光光度法测定ＭＴＸ含量及体外释放度。     

磁性药物载体在抗肿瘤方面的研究进展

通过外加磁场的引导作用,使负载抗癌药物的磁性载体靶向定位于靶区,提高靶组织的药物浓度,有效降低药物对正常组织或细胞的毒副作用及其他不良反应。磁性药物载体还具有靶向性、缓释、控释等优点,已成为了肿瘤靶向治疗常用的新型载体系统。本文综述了磁性药物载体磁性纳米颗粒、磁性脂质体、磁性微球在肿瘤治疗与诊断中的应用进展。     

免疫磁性制剂的研究

磁性药物制剂是将药物和铁磁性物质共包于或共分散于载体中应用于体内,然后利用体外磁场效应引导药物在体内移动并定位集中的靶向给药制剂。这类制剂包括:1 免疫磁性微球(immunomanetic microsphere) 制备此微球一般可分2步:①制成含磁性材料的微球;②在微球表面引入活性基因如OH,COOH,NH_2等,再通过载体表面偶联反应将抗体、酶或免疫毒素结合到载体上,     

磁性抗癌药物载体的研制

磁性微球抗癌药物载体在体外磁场的引导下,能定向移动和固定在肿瘤部位,本文采用单凝聚冻缩法制备出了直径为3～15μm 的磁性微球载体。载体中抗癌药含量为4.5～30%.     

多柔比星磁性葡聚糖微球的制备及特性检测

目的:制备多柔比星磁性葡聚糖微球并检测其特性。方法:采用吸附法制备多柔比星磁性葡聚糖微球。高倍显微镜观察微球粒径大小及形态,紫外分光光度法检测微球中多柔比星的含量,测定微球磁吸附率,计算求和值 S,确定最佳投料比(药物:载体),绘制药物微球体外释放曲线。结果:制备的多柔比星磁性葡聚糖微球最佳投料比为1:15,磁吸附率为100%。微球外形圆整,分散性好。多柔比星30 min 释放28%;60min 释放45%;6h 释放65%。结论:制备的多柔比星磁性葡聚糖微球缓释性好,磁响应性强,可作为一种治疗顽固性疼痛的靶向神经损毁剂。     

阿霉素磁性明胶微球的研究

报告了阿霉素磁性明胶微球（Ａｄｒ－ＭＧ－ｍｓ）的制备与性质，研究了超细氧化铁粒子的合成和磁性明胶微球（ＭＧ－ｍｓ）在狗体内的栓塞效果。阿霉素磁性明胶微球由２％阿霉素（Ａｄｒ）、６８％明胶和３０％的磁铁粒子组成，微球的平均粒径为２２μｍ。在体外实验中，药物释放速度证明微球有缓释的性质。磁铁粒子的平均粒径约为１０ｎｍ，磁性明胶微球与￣（９９ｍ）Ｔｃ标记磁性明胶微球通过导管分别输入狗的肝动脉内进行栓塞，照相和血管造影显示在未加外磁场时磁性明胶微球在左右肝叶分布几乎相等，而在１２００高斯的外磁场作用下，靶部位肝左叶的微球分布是肝右叶的２．２５倍，而甲状腺、脑、心脏的微球很微量，结果表明磁性明胶微球在外磁场作用下是一个很好的治疗肝癌的栓塞剂。     

5—氟脲嘧啶磁性微球的制备及其性能的探讨

将5—氟脲嘧啶，牛血清白蛋白和磁性液体混合乳化，在不同温度下固化，然后制成粒径l～2μm 的注射用磁性白蛋白微球(FMAM)．在体37℃的吐温80的生理盐水中。用各种不同固化温度的磁性微球进行释 放试验，结果表明：微球制备的固化温度越高，微球药物释放越缓慢。对磁性液体配比不同的微球药释试验结果 表明，磁性液体配比越高其释药越缓慢。另外，还对磁性徽球在不同磁感应强度下的磁应答性以及在小白鼠体内皮 下组织的分布情况作了初步研究.     

葡萄球菌蛋白A磁性微球的特异性细胞结合

蛋白A是从金黄色葡萄球菌衍生的一种蛋白质。作者等将此物质结合于磁性白蛋白微球骨架中,由于蛋白A可与大多数亚类免疫球蛋白G(IgG)中的Fc部分结合,产生可以联接针对特定细胞表面抗原的特异性免疫球蛋白,同时,在外界磁场的作用下,这些磁性微球可以聚集于特异的体内部位。本方法不仅避免利用化学耦联剂联接免疫球蛋白作用时间长、纯度要求高的缺点,而且还可利用磁性药物载体和免疫学方法的共同优点提供一条抗癌药物定位给药的新途径。本中详述了蛋白A磁性微球的制备和各种免疫球蛋白抗体与磁性微球的联接方法。利用~(51)Cr对鸡和羊     

阿霉素磁性高分子抗癌微球的制备与表征

本文以磁性Fe3O4超细微粒为核，阿霉素为模型药物，乙烯吡咯烷酮为基质，通过乳液聚合方法制备了磁性高分子抗癌微球。并对影响因素进行了考察。结果表明在Fe^3 ／Fe^2 为1．8：1，pH值为11，温度在70℃以上可制得单一的Fe3O4；而在微球的制备过程中，分散剂用量和搅拌速度是影响微球大小和形貌的关键因素。     

小球藻磁性碳中空微球作为药物缓释载体的开发和应用研究

目的 探究制备小球藻磁性碳中空微球的最佳条件及其装载诺氟沙星后的最佳控释条件。方法 采用水热碳化法合成了以Fe₃O₄为内核的磁性中空碳微球，并利用傅里叶红外光谱(FTIR)以及全自动比表面积和孔隙分析仪对微球进行表征测试。结果 FTIR结果显示微球的疏水性增加是藻壁纤维素亲水基团，如羧基、氨基均发生不同程度的减少造成的。通过全自动比表面积和孔隙度分析仪检测分析，有磁性碳化微球比表面积为0.596 m²/g，微球孔径为3.054 nm。在对诺氟沙星的缓释研究中发现，在pH=7.0时220℃条件下合成的磁性碳中空微球每毫克可以装载诺氟沙星186.32μg，该磁性碳中空微球可以在pH=8.0的环境下实现最优的诺氟沙星控释，3.6 h的累积释药率可达到31%。结论 磁性碳中空微球在pH=8.0的环境下对药物的缓释作用使诺氟沙星可以在肠道中停留较长时间，对肠道中的致病菌起到应有的灭杀作用，并达到了一定程度的靶向给药目的。     

A novel method to prepare magnetite chitosan microspheres conjugated with methotrexate (MTX) for the controlled release of MTX as a magnetic targeting drug delivery system

The purpose of the present study is to develop a new method to prepare magnetite chitosan microspheres conjugated with methotrexate (MTX) for the controlled release of MTX as a magnetic targeting drug delivery system. MTX was first conjugated to the chitosan chain via a peptide bond and then a suspension cross-linking technique was used for the production of magnetic chitosan microspheres with glutaraldehyde as the cross-linker. The MTX-loading capacity of the magnetic chitosan microspheres was determined and drug release experiments were also carried out to discuss the MTX release behavior. All the data support that the magnetic chitosan-MTX microspheres prepared in this method would have great potential application in magnetic targeting drug delivery technology.     

Preparation of magnetic gelatin microspheres for the targeting of drugs

Magnetically responsive gelatin microspheres for the targeting of drugs have been prepared using a water-in-oil emulsion technique with chemical cross-linking of the protein. The manufacturing variables affecting microsphere size, size distribution and surface characteristics have been examined as well as the magnetic responsivenessin vitro. Sesame oil was utilized for non-aqueous phase and magnetic gelatin microspheres of different size from 1.89 to 14.88 μm in mean diameter could be obtained with variation of HLB values of non-ionic surfactants. The content of magnetite which uniformly distributed throughout the microspheres was 26.7% (w/w). It was possible to control the localization of magnetic gelatin microspheres at specific sites within capillary models by using external magnetic field of under 5K gauss.     

In vitro and in vivo evaluation of targeting efficiency of Adriamycin hydrochloride magnetic microspheres

The objective of this study was to prepare magnetic microspheres as a targeting drug delivery system and to specifically evaluate its targeting efficiency. The magnetic microspheres were prepared by emulsion cross-linking techniques. Targeting efficiency was specifically investigated by experiments of biodistribution on rats and histological study. Adriamycin hydrochloride (ADR)-loaded magnetic microspheres were successfully prepared with the mean diameter of 3.853 μm (± 1.484 μm), and had its speciality of superparamagnetism. The results of the targeting efficiency study showed that application of the external magnetic field significantly increased the ADR concentration from 40.28 μg/ml to 100.70 μg/ml at 10?min, 36.99 μg/ml to 91.16 μg/ml at 60?min, and 13.71 μg/ml to 28.30 μg/ml at 180?min in liver as the targeting tissue. The relative uptake efficiencies in liver by injection treatment of ADR magnetic microspheres with external magnetic field were 3.87, 5.59, and 3.34 at 10?min, 60?min, and 180?min after administration, respectively. In conclusion, distinguished targeting efficiency was displayed, which indicated that the magnetic microspheres could be applied as a novel targeting drug delivery system.     

In vitro and in vivo evaluation of targeting efficiency of Adriamycin hydrochloride magnetic microspheres

The objective of this study was to prepare magnetic microspheres as a targeting drug delivery system and to specifically evaluate its targeting efficiency. The magnetic microspheres were prepared by emulsion cross-linking techniques. Targeting efficiency was specifically investigated by experiments of biodistribution on rats and histological study. Adriamycin hydrochloride (ADR)-loaded magnetic microspheres were successfully prepared with the mean diameter of 3.853 μm (± 1.484 μm), and had its speciality of superparamagnetism. The results of the targeting efficiency study showed that application of the external magnetic field significantly increased the ADR concentration from 40.28 μg/ml to 100.70 μg/ml at 10?min, 36.99 μg/ml to 91.16 μg/ml at 60?min, and 13.71 μg/ml to 28.30 μg/ml at 180?min in liver as the targeting tissue. The relative uptake efficiencies in liver by injection treatment of ADR magnetic microspheres with external magnetic field were 3.87, 5.59, and 3.34 at 10?min, 60?min, and 180?min after administration, respectively. In conclusion, distinguished targeting efficiency was displayed, which indicated that the magnetic microspheres could be applied as a novel targeting drug delivery system.     

Physiological pharmacokinetic model of adriamycin delivered via magnetic albumin microspheres in the rat

The influence of magnetic albumin microspheres on the disposition of adriamycin was evaluated. Adriamycin concentrations were monitored in multiple rat tissues for 48 hr after its intra-arterial administration (2 mg/kg) as a solution and associated with magnetic albumin microspheres. The magnetic dosage form was targeted to a predefined tail segment with a magnetic field strength of 8000 G applied for 30 min after dosing. A physiological pharmacokinetic model was used to describe the disposition of adriamycin following its administration from either dosage form. The model developed for the data resulting from administration of adriamycin as a solution served as a foundation for the model developed for adriamycin resulting from the administration of adriamycin associated with the magnetic dosage form. The model for adriamycin following administration of the magnetic microspheres required additional relationships to describe the transport of adriamycin associated with the microspheres. For both models, the predicted adriamycin concentrations were in adequate agreement with the observed values. The present investigation demonstrates the use of a physiological pharmacokinetic modeling method to represent drug kinetics following its administration via a targeted drug delivery system.     

Physiological pharmacokinetie model of adriamycin delivered via magnetic albumin microspheres in the rat

The influence of magnetic albumin microspheres on the disposition of adriamycin was evaluated. Adriamycin concentrations were monitored in multiple rat tissues for 48 hr after its intra-arterial administration (2 mg/kg) as a solution and associated with magnetic albumin microspheres. The magnetic dosage form was targeted to a predefined tail segment with a magnetic field strength of 8000 G applied for 30 min after dosing. A physiological pharmacokinetic model was used to describe the disposition of adriamycin following its administration from either dosage fcrm. The model developed for the data resulting from administration of adriamycin as a solution served as a foundation for the model developed for adriamycin resulting from the administration of adriamycin associated with the magnetic dosage form. The model for adriamycin following administration of the magnetic microspheres required additional relationships to describe the transport of adriamycin associated with the microspheres. For both models, the predicted adriamycin concentrations were in adequate agreement with the observed values. The present investigation demonstrates the use of a physiological pharmacokinetic modeling method to represent drug kinetics following its administration via a targeted drug delivery system.Research support from the Medical Research Council of New Zealand is gratefully acknowledged.     

磁性靶向紫杉醇微球制备的初步研究

目的：制备磁性靶向紫杉醇微球.方法：以紫杉醇和纳米Fe3O4为材料制备出磁性靶向紫杉醇微球,并利用高分辨透射电子显微镜（HRTEM）观察微球的形貌,同时采用紫外可见分光光度法测定微球的载药量和包封率.结果：磁性靶向紫杉醇微球的载药量为3.013%,包封率为35.26%.结论：通过实验研究制备了磁性紫杉醇微球,具有靶向定位功能,形成一种磁靶向给药系统.     

Hydroxy-urea bearing albumin microspheres--preparation, characterization and evaluation

Hydroxy-urea bearing albumin microspheres were prepared using the polymer dispersion method. Glycerol was used successfully in place of water as an internal phase of w/o emulsion, to prepare HSA based albumin microspheres. Silicone coated magnetite of nanometeric size was incorporated in the drug bearing microspheres. The process variables which could affect the physical characteristics with respect to in vitro and in vivo performance of the prepared microspheres were studied. The in vitro release of the drug from the microspheres followed a linear relationship when commulative per cent drug release was plotted against square root of time. Microspheres of average size 1-4 microns were studied for in vivo distribution and localization. It was established that 67 per cent of the drug enveloped in magnetic albumin microspheres could be localized in a rat tail target segment, on applying an external magnetic field of strength 8000 Oe. A remarkable stabilization of hydroxy urea in the prepared microspheres was recorded when t10% drug degradation was compared with the albumin microspheres prepared by a conventional emulsion polymerization method using water as an internal phase.     

Ultrasonically controlled release and targeted delivery of diclofenac sodium via gelatin magnetic microspheres

In the present work, an attempt was made to target diclofenac sodium to its site of action through magnetic gelatin microspheres. The gelatin magnetic microspheres loaded with 8.9% w/w of diclofenac sodium and 28.7% w/w of magnetite were formulated by emulsification/cross-linking with glutaraldehyde. The formulated microspheres were characterized by particle size distribution, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and in vitro release studies. The in vivo distribution and targetability of gelatin magnetic microspheres after i.v. administration were studied in rabbits. The formulated microspheres were below 5 microm and spherical in nature as evidenced by the SEM photographs. DSC and X-ray diffraction studies revealed the absence of drug-polymer interaction. Encapsulated diclofenac sodium was released slowly more than 18 days. Application of sonication, as external stimuli to enhance drug release, during release study, has slightly increased the release rate. The formulated microspheres were injected intravenously after keeping a suitable magnet near the target area. The quantity of drug available at the target and non-target area was determined by HPLC. About 5.5% of injected dose localized near the target organ. Majority of injected dose was recovered from lungs, spleen and liver indicating localization of microspheres in these organs. Further studies are required to improve the targeting efficiency of gelatin microspheres by modifying surface properties to overcome phagocytosis and by selecting suitable particle size to avoid the entrapment of microspheres in non-target organs.     

Drug targeting using non-magnetic and magnetic albumin-globulin mix microspheres of mefenamic acid

Optimum conditions for the preparation of non-magnetic and magnetic microspheres of albumin-globulin mix (alglomix) containing mefenamic acid have been standardized. The effect of various parameters has been investigated with regard to the appearance, yield, drug content and encapsulation efficiency. The physicochemical parameters of the microspheres such as density, particle size distribution, surface topography and wall thickness, as well as the magnetite contained within the magnetic microspheres, have been determined. The infrared spectroscopic analysis confirmed the encapsulation of the drug and absence of free drug on the surface of the microspheres. The X-ray diffraction analysis confirmed that the crystallinity of the drug remained unchanged indicating thereby that no complex formation had taken place between core and coat materials. The in vitro release profiles of the microspheres have been studied. An attempt has also been made to check the in vivo efficacy in rats.