Acute effect of tetrandrine pulmonary targeting microspheres on hypoxic pulmon ary hypertension in rats

目的　评价汉防己甲素 (Tet)肺靶向微球对低氧性肺动脉高压的治疗效应及其对肺循环的选择性作用。方法　 2 0只大鼠经低氧处理 3周 ,另 10只大鼠作为正常对照。对 10只低氧大鼠给予Tet肺靶向微球 ,对 10只低氧大鼠和 10只正常大鼠给予Tet水溶剂。以右心导管法测定大鼠肺动脉平均压 (mPAP) ,经左股动脉插管测定体循环平均压 (mSBP)。结果　低氧后大鼠出现了肺动脉高压。大鼠应用Tet肺靶向微球后 ,其mPAP的降低较Tet水溶剂治疗组更为明显 (P <0 0 5 ) ,且作用持续时间明显延长 ;与Tet水溶剂不同 ,应用Tet微球后大鼠mSBP无显著变化。结论　Tet肺靶向微球对肺循环具有较好的选择性 ,可明显增强Tet降低mPAP的效应。     

鸡新城疫病毒口服微球的制备研究

目的:研究口服疫苗微球的最佳制备工艺。方法:以鸡新城疫病毒(NDV)作为疫苗模型药物、乳酸-羟基乙酸共聚物(PLGA)为载体材料,采用W/O/W复乳-溶剂挥发法制备NDV-PLGA口服微球。采用正交设计试验,考察活NDV体积、PL GA浓度、初乳搅拌速度、内水相中的保护剂对微球形状、粒径、粘连情况和药物活性的影响,其中以血凝法测定微球中释放药物的效价。结果:NDV口服微球的最佳制备工艺系活NDV体积为200μl、PLGA浓度为4%、初乳搅拌速度为8000r/min、内水相中的保护剂为牛血清白蛋白。结论:本方法为制备口服疫苗微球的最佳制备工艺。     

曲尼司特微球对兔晶状体后囊膜混浊的抑制作用

目的观察曲尼司特微球(tranilastMS)对兔眼晶状体超声乳化术后后囊膜混浊的抑制作用。方法将47只兔眼随机分为8组,均行超声乳化晶状体摘除术,术毕除空白对照组外均一次性囊袋内注入含不同药物的0.1ml混悬介质,所含物分别为2mg、1mg、0.5mgtranilastMS,1.85mg空白微球,0.06mg地塞米松缓释剂,0.15mgtranilast原料药,0.1ml混悬介质囊袋内注入为对照组之一。术后按时检查前房反应并测量眼压。术后第1个、第2个、第3个月对术眼进行拍照,获得后囊膜混浊图像,分析后囊膜混浊指数,并进行统计学比较。术后第3个月摘取术眼行组织病理学检查。结果术后除空白对照组外,余组前房内反应均较重,持续时间较长,各组眼压无明显增高。对后囊膜混浊指数进行统计学比较显示,含tranilastMS的后囊膜混浊较轻,与其他组比较差异有显著性(P<0.05),不同浓度tranilastMS组之间差异也有显著性。光镜显示术后第3个月用药组后囊膜光滑,无明显增殖,电镜显示用药组及非用药组角膜和虹膜超微结构无明显变化。结论曲尼司特微球在实验期内可以抑制后囊膜混浊的发生和发展,作用呈浓度依赖性,对眼内其他组织无明显毒副作用。     

微球的制备和表征

目的制备葡激酶突变体(K35R，DGR)的聚乳酸-羟基乙酸(PLGA)微球，使其在包封和释放过程中都能保持活性。方法使用复乳溶剂挥发法制备DGR的PLGA微球，研究了搅拌速度、PLGA浓度、内水相和外水相中的添加剂对蛋白包封率以及微球性质的影响，并进行了DGR微球的体外和体内释放试验。结果2%聚乙烯醇可以有效抑制超声乳化时DGR在水/二氯甲烷界面上的变性，将DGR的活性回收率从16%提高到几乎100%。在外水相中加入NaCl可以显著提高蛋白包封率，同时对微球的粒径分布和表面形态也产生了重要影响。DGR微球的体外释放呈现两个时相，15 d释放大约DGR总活性的50%。DGR微球在体内持续释放5 d。结论制备的PLGA微球，DGR包封率高，稳定性较好，是DGR的良好载药系统。     

阿霉素明胶微球的制备及体外释药特性

目的对阿霉素明胶微球(ADM-GMS)的制备工艺及体外释药特性进行研究.方法用乳化交联法制备阿霉素明胶微球,采用正交试验设计法考察影响制备工艺的各因素.用扫描电镜观察微球表面形态.并对阿霉素明胶微球的粒径大小及其分布、载药量、包封率、体外释药、稳定性等进行了测定.结果微球形态圆整,大小均匀、表面光滑,平均粒径为69.154μm,87.32%的微球粒径分布在50～120μm.微球平均载药量为2.13%,包封率为42.62%.微球体外降解和释药特性满足要求,且37℃下性质稳定.结论该制备工艺稳定,制得的阿霉素明胶微球有望成为临床用动脉栓塞术治疗癌症的新制剂.     

肺靶向炎琥宁明胶微球的制备

 目的对炎琥宁肺靶向明胶微球的处方、工艺、释药特性及其体内靶向性进行研究。方法以生物降解材料明胶为载体,采用乳化交联法制备炎琥宁明胶微球;单因素考察的基础上,利用正交实验设计筛选最佳处方和工艺;考察其体外释药特性;兔耳缘静脉注射微球后,取肺组织切片,体内试验结果初步考察其肺靶向性。结果所制备的炎琥宁明胶微球外形圆整,大小均匀,平均粒径为17.14μm,载药量为2.08%,包封率为70.94%;1.5 h体外释放50%左右,12 h可达90%以上。体内试验结果初步验证其具有一定肺靶向性。结论筛选的最佳处方工艺可制备性质优良的炎琥宁肺靶向明胶微球。     

壳聚糖-海藻酸钠布洛芬缓释微球的制备工艺及性能

目的 研究以壳聚糖和海藻酸钠为基质材料,制备布洛芬缓释微球. 方法 以微球的药物包封率为制备工艺优化指标.利用复凝聚法,通过L16(45)正交实验得出微球的最佳制备工艺条件. 结果 壳聚糖浓度4.0 mg/mL,搅拌速度600 r/min,反应温度30℃,体系pH 4.5,交联剂戊二醛用量1.5 mL为最佳工艺.以最佳制备工艺条件制备的布洛芬缓释微球.粒径(31.6±1.7)μm,药物包封率(64.6±2.2)%. 结论 微球球形态及稳定性较好,有良好的缓释效果.     

抗人大肠癌免疫磁性白蛋白微球的抗癌效果

目的:观察自制丝裂霉素C免疫磁性白蛋白微球(MMC-IMAMS)体外及体内抗大肠癌效果。方法:将丝裂霉素C免疫磁性白蛋白微球(MMC-IMAMS)与丝裂霉素C磁性白蛋白微球(MMC-MAMS)、单纯丝裂霉素C(MMC)比较,MTT法分别检测其体外对大肠癌细胞株LoVo的杀伤作用,然后通过移植人大肠癌裸鼠模型检测体内的肿瘤抑制率。结果:体外实验丝裂霉素免疫磁性白蛋白微球较单纯丝裂霉素磁性白蛋白微球有更强的肿瘤细胞抑制效率;裸鼠模型体内实验丝裂霉素免疫磁性白蛋白微球组肿瘤抑制率较丝裂霉素磁性白蛋白微球组和单纯丝裂霉素组具有显著差异。且丝裂霉素免疫磁性白蛋白微球是安全的,在体外磁场作用下可较长时间内沉积于靶区。结论:丝裂霉素免疫磁性白蛋白微球安全性好,靶向性更强大,体内体外均有更强的抗癌效果。     

Visual Evidence of Acidic Environment Within Degrading Poly(lactic-co-glycolic acid) (PLGA) Microspheres

Purpose. In the past decade, biodegradable polymers have becomethe materials of choice for a variety of biomaterials applications. Inparticular, poly(lactic-co-glycolic acid) (PLGA) microspheres havebeen extensively studied for controlled-release drug delivery. However,degradation of the polymer generates acidic monomers, andacidification of the inner polymer environment is a central issue in thedevelopment of these devices for drug delivery. Methods. To quantitatively determine the intrapolymer acidity, weentrapped pH-sensitive fluorescent dyes (conjugated to 10,000 Dadextrans) within the microspheres and imaged them with confocalfluorescence microscopy. The technique allows visualization of thespatial and temporal distribution of pH within the degradingmicrospheres (1). Results. Our experiments show the formation of a very acidicenvironment within the particles with the minimum pH as low as 1.5. Conclusions. The images show a pH gradient, with the most acidicenvironment at the center of the spheres and higher pH near the edges,which is characteristic of diffusion-controlled release of the acidicdegradation products.     

Effect of the Concurrent LHRH Antagonist Administration with a LHRH Superagonist in Rats

Purpose. The purpose of this study was to investigate the effect of anovel LHRH antagonist, Orntide acetate, on the initial testosteroneelevation in rats during treatment with a LHRH superagonist,Leuprolide acetate.Methods. Thirteen groups of a rat animal model were administeredeither liquid Orntide or Orntide PLGA microspheres before or simultaneouslywith Leuprolide injections. Serum levels of testosterone weremonitored during the time course of the study using a radioimmunoas say method.Results. Administration of a single daily dose of liquid Orntide resultedin testosterone suppression within 6 h to levels below 0.5 ng/ml(castration level). However, combined administration of liquid Orntide andliquid Leuprolide did not have a significant effect on the initialtestosterone elevation in studied rats. Similarly, there was no effect when liquidOrntide was co-administered with Leuprolide microspheres. Administrationof Orntide microspheres 48 h before Leuprolide microspheressuppressed testosterone levels below the castration level within 24 h,however, did not prevent a rise in testosterone serum concentration uponadministration of Leuprolide microspheres. Also, a second testosteronepeak was observed between days 3 and 15 in the animals which weresimultaneously treated with Orntide microspheres and Leuprolidemicrospheres.Conclusions. Orntide acetate was found to be an effective LHRHantagonist with a rapid onset of pharmacological action and a shortbiological half-life. Administration of a single dose of liquid Orntideor Orntide microspheres, resulted in rapid testosterone suppressionwithout an initial elevation, as seen with LHRH superagonists. However,combined administration of Orntide and Leuprolide did not havean effect on the initial testosterone elevation in rats.