激光微探针飞行时间质谱测定白蛋白微球制剂的组分

目的 :测定5 %声振人血白蛋白微球制剂中的各组成成分。方法 :采用激光微探针飞行时间质谱仪分别测定内标物、声振前后各组。结果 :得出各组质谱图 ,并给出峰分子量。结论 :5 %声振人血白蛋白微球制剂声振过程仅产生白蛋白表面电荷数的改变 ,未见其它变化。     

新型左心声学超声造影剂空气白蛋白微球制剂的研制

目的 :对空气人血白蛋白微球制剂的制备工艺进行研究 ,并初步探讨微球形成机理。方法 :按正交设计筛选最佳制备工艺条件 ;库尔特颗粒分析仪测定最佳制备工艺条件下微球粒径 ;光、电镜考察微球外观形态。结果 :最佳制备工艺 :白蛋白生理盐水溶液浓度为5 % ,声振仪功率为9档 ,声振持续时间为60秒。结论 :通过正交试验设计 ,成功研制出含空气的白蛋白微球 ,并能有效地用于左心靶向超声显影诊断     

正交设计优化八氟丙烷白蛋白微球混悬液的制备工艺

目的优化八氟丙烷白蛋白微球混悬液的制备工艺。方法以微球的平均直径和浓度为考察指标,以八氟丙烷通气量、声振强度和终点温度作为工艺条件进行三因素三水平的正交试验。结果最佳工艺条件为采用1％人血白蛋白溶液20mL,声振强度90％,5s内通入八氟丙烷2mL,终点温度77℃。结论采用该最佳工艺制备的八氟丙烷白蛋白微球混悬液,微球浓度高而且稳定。     

新型微量气体容量仪测定人血白蛋白空气微球的空气含量

５％声振人血白蛋白注射液是由５％白蛋白生理盐水溶液经特殊处理,形成包裹空气的白蛋白微球制剂,经静脉途径用于心脏显影和其它体内诊断,效果显著［１～３］。国外同类产品中如Ａｌｂｕｎｅｘ（美国ＭａｌｌｉｎｋｒｏｄｔＭｅｄｉｃａｌ公司）等已广泛用于临床,深受...     

3种方法分析白蛋白空气微球的球壁蛋白

采用高效液相色谱（HPLC）、醋酸纤维膜电泳和半微量定氮法测定5％声振人血白蛋白空气微球制剂中球壁蛋白的含量。HPLC确证了球壁蛋白主要成分为人血白蛋白；醋酸纤维膜电泳测定空气人血白蛋白微球制剂中人血白蛋白纯度＞90％；半微量定氮法测出球壁蛋白含量为3．56％左右，99％正常值范围为2．52％～4．60％。     

阿霉素磁性白蛋白微球的大鼠体内释药研究

作者研究了阿霉素磁性白蛋白微球在靶位及其它组织内的处置。制备将含有100mg磁铁矿粉末的25～35%W/W混悬液及200μl盐酸阿霉素溶液(50mg/ml)加至250μl牛血清白蛋白溶液(400mg/ml)中混匀,再加棉子油30ml,在4℃下用125W超声处理2分钟得到磁性乳液,将此磁乳以每分钟100±10滴的速度滴加至120±5℃的棉子油100 ml中,在1500rpm的转速下继续保温搅拌10分钟,再将此混合液迅速冷却至20℃,用无水醚洗涤4次,然后用倾泻法在300-G巴的外磁场作用下,将未乳化磁铁矿沉淀与阿霉素磁性白蛋白微球分离,最后将磁性白蛋白微球制     

米托蒽醌白蛋白微球和联糖米托蒽醌白蛋白微球肝靶向性比较研究

目的：比较米托蒽醌白蛋白微球和联糖米托蒽醌白蛋白微球肝靶向性的优劣。方法：以小鼠为实验动物,以静脉注射给药后小鼠血浆及各器官中的米托蒽醌含量为指标。结果：联糖米托蒽醌白蛋白微球在肝中的分布高于米托蒽醌白蛋白微球,而且肝中米托蒽醌较高浓度的维持时间也更长。结论：联糖米托蒽醌白蛋白微球肝靶向性比米托蒽醌白蛋白微球好,但无统计学上的显著性差异。     

单克隆抗体BDI－I导向的阿霉素白蛋白毫微球对人膀胱癌细胞的特异杀伤活性

用化学偶联法将抗人膀胱癌单克隆抗体分子偶联到阿霉素白蛋白毫微球上，构建了一个有靶向杀伤性的免疫毫微球，即：阿霉素白蛋白载单克隆抗体毫微球（ＡＤＲ－ＮＰ－Ａｂ）。改变阿霉素毫微球和单克隆抗体的反应分子比，确定了制备该免疫毫微球的最佳条件。经免疫荧光检测及显微照像分析证明，免疫毫微球可有效地和人膀胱癌细胞结合。体外杀伤试验表明，此免疫毫微球对靶细胞ＥＪ有高度特异杀伤活性，而对无关的人直肠癌Ｌｏｖｏ细胞则无明显作用。     

多层海藻酸-壳聚糖聚电解质膜微球的制备与体外释放特性研究

目的：制备牛血清白蛋白-海藻酸-壳聚糖微球（BSA-ACM）,牛血清白蛋白-海藻酸-壳聚糖-海藻酸钠微球（BSA-ACAM）,牛血清白蛋白-海藻酸-壳聚糖-海藻酸-壳聚糖-海藻酸钠微球（BSA-ACACAM）。方法：以海藻酸钠和壳聚糖溶液为囊材,对BSA进行反复包裹,采用乳化-交联法制备BSA-ACM、BSA-ACAM、BSA-ACACAM;采用扫描电镜测定微球粒径,Micro-BCA试剂盒测定载药量,考察包封率和24h体外释药特性,并进行Higuchi方程拟合。结果：BSA-ACM、BSA-ACAM、BSA-ACACAM微球球形圆整,分散性好,平均粒径分别为（3.79±1.33）、（3.52±0.96）、（3.07±1.17）μm;载药量分别为（17.97±1.33）%、（16.95±0.46）%、（16.47±1.49）%;包封率分别为（65.78±4.98）%、（63.99±4.83）%、（55.00±1.50）%。微球体外释放速率与聚电解质膜包裹层数呈负相关,均符合Higuchi方程（r分别为0.9787、0.9869、0.9808）,24h内累积释放量分别为32.15%、25.59%、16.72%,无明显突释现象。结论：多层海藻酸-壳聚糖聚电解质膜微球能减少药物的突释,具有良好的缓释效果。     

单克隆抗体BDI-I导向的阿霉素白蛋白毫微球对人膀胱癌细胞的特异杀伤活性

用化学偶联法将抗人膀胱癌单克隆抗体分子偶联到阿霉素白蛋白毫微球上,构建了一个有靶向杀伤性的免疫毫微球,即:阿霉素白蛋白载单克隆抗体毫微球(ADR-NP-Ab)。改变阿霉素毫微球和单克隆抗体的反应分子比,确定了制备该免疫毫微球的最佳条件。经免疫荧光检测及显微照像分析证明,免疫毫微球可有效地和人膀胱癌细胞结合。体外杀伤试验表明,此免疫毫微球对靶细胞EJ有高度特异杀伤活性,而对无关的人直肠癌Lovo细胞则无明显作用。     

盐酸克仑特罗双层缓释片的研制及体内外评价

目的研制盐酸克仑特罗缓释双层片并考察其体外释放及犬体内药动学。方法以羟丙甲纤维素和乙基纤维素为骨架材料,分别采用粉末直接压片和湿法制粒技术制备盐酸克仑特罗双层缓释片。测定其体外释放度和Beagle犬口服单剂量盐酸克仑特罗普通片和双层缓释片后血浆中药物的浓度,推算药动学参数。结果盐酸克仑特罗双层缓释片体外释放符合Higuehi方程。盐酸克仑特罗双层缓释片和普通片的有关药动学参数如下：t1/2分别为（11．90±1．42）,（6．18±0．81）h;Cmax为（5．86±0．33）,（11．43±0．64）ng·mL^-1;tmax为（3．17±0．73）,（2．02±0．35）h;AUC0～1．为（65．08±2．63）,（68．00±2．89）ng·h·mL^-1。结论盐酸克仑特罗双层缓释片体外具有明显的速释和缓释特性。体内平均滞留时间长于普通片。体外释放和体内吸收有良好的相关性。     

Effects of polymer,organic solvent and mixing strength on integrity of proteins and liposomes encapsulated in polymeric microspheres fabricated by the double emulsion process

The double emulsion process has commonly been applied to encapsulate water-soluble bioactive agents into polymeric microspheres. However, the integrity of many of these agents may be destroyed by the highly energetic procedures such as sonication that are routinely used to produce stable water-in-oil (w/o) emulsion. The aim of this research was to pursue the possibility of replacing the sonication by a mild emulsification procedure such as vortex mixing, with the use of certain materials to help to obtain stable w/o emulsion. The following materials were examined: poly(lactide-co-ethylene glycol) (PELA) as the polymer, ethyl acetate and acetone as the solvents, poly(vinyl alcohol) (PVA) and d-α tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS) as the emulsifiers in w/o emulsion. The experimental results, with human serum albumin (HSA) as the encapsulated agent, showed that, when vortex mixing was used, these materials could significantly improve w/o emulsion stability and help to obtain satisfactory encapsulation effects, i.e. high encapsulation efficiency (EE) and low initial release burst. A delicate structure, i.e. liposomes, which is very sensitive to sonication, was then incorporated into microspheres by the ‘modified double emulsion process’. It was found that the liposomes were intact and the encapsulation effects were good. Therefore, it can be concluded that the modified double emulsion process could be advantageous for the encapsulation of delicate substances.     

Screening for Oxidative Stress Elicited by Engineered Nanomaterials: Evaluation of Acellular DCFH Assay

The DCFH assay is commonly used for measuring free radicals generated by engineered nanomaterials (ENM), a well-established mechanism of ENM toxicity. Concerns exist over susceptibility of the DCFH assay to: assay conditions, adsorption of DCFH onto ENM, fluorescence quenching and light scattering. These effects vary in magnitude depending on ENM physiochemical properties and concentration. A rigorous evaluation of this method is still lacking. The objective was to evaluate performance of the DCFH assay for measuring ENM-induced free radicals. A series of diverse and well-characterized ENM were tested in the acellular DCFH assay. We investigated the effect of sonication conditions, dispersion media, ENM concentration, and the use of horseradish peroxidase (HRP) on the DCFH results. The acellular DCFH assay suffers from high background signals resulting from dye auto-oxidation and lacks sensitivity and robustness. DCFH oxidation is further enhanced by HRP. The number of positive ENM in the assay and their relative ranking changed as a function of experimental conditions. An inverse dose relationship was observed for several Carbon-based ENM. Overall, these findings indicate the importance of having standardized assays for evaluating ENM toxicity and highlights limitations of the DCFH assay for measuring ENM-induced free radicals.     

Effects of polymer, organic solvent and mixing strength on integrity of proteins and liposomes encapsulated in polymeric microspheres fabricated by the double emulsion process

The double emulsion process has commonly been applied to encapsulate water-soluble bioactive agents into polymeric microspheres. However, the integrity of many of these agents may be destroyed by the highly energetic procedures such as sonication that are routinely used to produce stable water-in-oil (w/o) emulsion. The aim of this research was to pursue the possibility of replacing the sonication by a mild emulsification procedure such as vortex mixing, with the use of certain materials to help to obtain stable w/o emulsion. The following materials were examined: poly(lactide-co-ethylene glycol) (PELA) as the polymer, ethyl acetate and acetone as the solvents, poly(vinyl alcohol) (PVA) and d-alpha tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS) as the emulsifiers in w/o emulsion. The experimental results, with human serum albumin (HSA) as the encapsulated agent, showed that, when vortex mixing was used, these materials could significantly improve w/o emulsion stability and help to obtain satisfactory encapsulation effects, i.e. high encapsulation efficiency (EE) and low initial release burst. A delicate structure, i.e. liposomes, which is very sensitive to sonication, was then incorporated into microspheres by the 'modified double emulsion process'. It was found that the liposomes were intact and the encapsulation effects were good. Therefore, it can be concluded that the modified double emulsion process could be advantageous for the encapsulation of delicate substances.     

去甲斑蝥素白蛋白微球在大鼠体内的药动学及组织分布研究

目的：研究去甲斑蝥素（NCTD）白蛋白微球在大鼠体内的药动学及组织分布情况。方法：以市售去甲斑蝥素注射液为参比,测定NCTD白蛋白微球在大鼠体内血浆中的药动学模型及药动学参数,用靶向效率来评价其在大鼠体内的组织分布及靶向性。结果：NCTD白蛋白微球在大鼠体内的药动学模型符合二室模型,主要药动学参数为：t_（1/2α）=（0.57±0.11）h,t1/2β=（20.69±1.06）h,CL=（0.016±0.002 4）ml·h·kg^-1,AUC0～∞=（63.41±9.08）mg·h·L^-1,其在肝脏,脾脏,心脏及肾脏的靶向效率分别为为2.36,1.78,0.43和0.35。结论：与去甲斑蝥素注射液相比,NCTD白蛋白微球能提高对肝脏,脾脏的趋向性,减少对肾脏及心脏的分布,有利于提高其治疗作用,减少不良反应。     

米托蒽醌白蛋白微球和糖蛋白微球的体外释药规律

目的：考察米托蒽醌白蛋白微球和米托蒽醌联糖白蛋白球的体外释药规律。方法：采用动脉透析法释药,分光光度法测定米托蒽酯含量。结果：二者在体外释药符合双指数双相动力学规律,但后者达释药平衡快（约6小时）,累积释放量几科比前者小一倍。结论：两种微球的累积药分数经单因数经单因数经方差分析,具有显著差异。     

Ciprofloxacin-loaded bovine serum albumin microspheres: preparation and drug-release in vitro.

Ciprofloxacin albumin microspheres were prepared by the spray drying technique, with bovine serum albumin as the natural biodegradable wall material. The spherical microspheres, flowed well, were organic solvent free and in the size range 1-5 microm. The drug release from the microspheres could be retarded by further thermal denaturation. The sustained-release microspheres were suitable for dry powder inhaled lung drug delivery systems.     

黄芩茎叶总黄酮对铝中毒小鼠记忆障碍的作用

目的研究黄芩茎叶总黄酮(TotalflavonoidsfromstemsandleavesofScutellariabaicalensisGeorgi,SSF)对慢性铝中毒小鼠学习记忆运动障碍、神经和肝脏病理改变及自由基不正常变化的作用。方法小鼠腹腔注射(Introperitonealinjection,ip)AlCl350d制备铝中毒模型。通过小鼠学习记忆能力、自主活动、皮层和肝脏病理改变及脑肝脏丙二醛(malondialdehyde,MDA);超氧化物岐化酶(superoxidedismutase,SOD)测定,评价SSF对小鼠慢性铝中毒的作用。结果与空白对照组相比,AlCl3(100mg·kg-1,ip,50d)使小鼠学习记忆能力降低、自主活动次数减少、皮层和肝脏细胞病理改变、脑和肝脏MDA水平增加和SOD活性减低。SSF50、100和200mg·kg-1不同程度的改善铝中毒小鼠上述病理改变。结论SSF能够改善慢性铝中毒小鼠学习记忆运动障碍、神经肝脏病理改变和自由基不正常变化。