盐酸川芎嗪肺靶向微球的研究

用乳化法制备盐酸川芎嗪明肢微球,优化了工艺。对微球的外观、粒径与其分布、含量、体外释药、稳定性及体内分布等进行研究。结果表明平均粒径为12.65μm,粒径范围5.0～24.9μm占总数的87.5%,球内含药量平均为16.49%±0.49%(n=3),冰箱或室温放置稳定,体外释药符合一级动力学规律,释药t_1/2比原药延长约5倍。小鼠静注微球后20 min,在肺内的相对分布百分率明显高于其它组织与血液,与溶液对照组相比,提高近6倍。     

肺靶向卡铂明胶微球的研究

目的:为提高卡铂的疗效,降低毒副作用,制备了该药的明胶微球。方法:用乳化法制备卡铂明胶微球,紫外分光光度法测定药物的含量,二阶导数法测定体外释药情况;用静脉注射肿瘤细胞建立了肺肿瘤模型,计算瘤结节数来考察疗效。结果:卡铂明胶微球平均粒径为13-20 μm ,粒径范围5-0～28-6 μm 的微球数占总数的91-8% 。微球平均载药量为23-76%(n=3) 。冰箱、室温和37℃,RH75% 考察3个月,几乎无变化,体外释药符合一级动力学规律,释药T_1/2 比原药延长约10倍。药效学实验表明,卡铂明胶微球对小鼠肺部S180肿瘤生长有明显的抑制作用,抑瘤作用较原药卡铂大大提高。结论:卡铂明胶微球在体内有良好的肺靶向性,对提高药物的疗效,降低药物毒副作用等方面有重大意义。     

肝靶向米托蒽醌白蛋白微球的研究

用乳化—热固化法制备了米托蒽醌白蛋白微球,并对其形态、大小及其分布、微粉学性质、载药性能、体外释药、稳定性和体内分布进行了研究。结果表明,该载药微球的平均算术径为0.99μm,平均表面径为1.24μm,平均容积径为1.44μm;表观载药量为2.558%±0.101%;有效载药量为1.503%±0.127%;包封率为92.82%±4.60%;体外释药符合双相动力学规律,释药方程为1-Q=0.6428e^-0.2132t+0.3988e^-000150t(γ₁=-0.9951,γ₂=-0.9982);T_1/2α=3.250h,T_1/2β=461.7h;室温放置3个月,微球形态、药物含量等均无明显变化。HPLC测定表明,小鼠尾iv该微球20min内即有77.6%±1.38%的药物浓集于肝脏,具有明显的肝靶向性。提示米托蒽醌白蛋白微球有可能提高米托蒽醌的抗肝癌效果和降低其全身毒副作用。     

紫杉醇肺靶向微球的制备及体内外评价

目的用生物可降解材料聚乳酸-聚羟基乙酸共聚物(PLGA)制备肺靶向紫杉醇缓释微球。方法在单因素考察的基础上进行正交试验设计,筛选出肺靶向紫杉醇PLGA微球的最佳制备工艺条件;利用桨板法研究了微球的体外释药规律;用小鼠为实验对象,研究了紫杉醇聚乳酸微球的体内组织药物分布。结果制得的微球形态圆整,粒径在5~15μm范围内的占总体积的87.18%,微球平均粒径为9.65μm;包封率为83.8%;载药量为19.7%;体外释药符合Higuchi方程Q=-2.193 7 22.009t0.5,r=0.990 4;体内实验表明紫杉醇微球混悬剂较普通注射剂更趋于聚集在肺组织。结论微球制备工艺稳定,具有明显的缓释作用和肺靶向性。     

新型可降解聚酯材料地西泮缓释微球的研制

目的　优化制备工艺,用新型的生物可降解材料聚羟基丁酸酯—羟基戊酸酯共聚物（PHBV）与D,L-聚乳酸（PLA）共混物为基材制备以地西泮（diazepam,DZP）为模型药物的缓释微球（MS）。方法　用正交设计优化微球制备工艺,用扫描电镜（SEM）观察微球表面形态。对微球粒径及其分布、体外释药、稳定性及在动物体内药动学进行了测定。结果　微球平均粒径为(20.45±4.50) μm,粒径在15.5～35.2 μm占总数88%以上。载药量为(16.95±0.80)%,包封率为(69.68±1.13)%;体外释药方程为Q=2.7027t+13.50(γ=0.9827),动物体内实验表明,微球的血药浓度-时间曲线下面积AUC是溶液对照组的2.35倍,平均驻留时间MRT是对照组的3.62倍。微球在冰箱4℃与室温（20～25℃）条件下性质稳定。结论　微球制备工艺稳定,与DZP针剂相比,具有明显缓释作用。     

羟基喜树碱微球的制备及其小鼠体内分布研究

目的:制备肺靶向性羟基喜树碱(HCPT)微球,评价其体外释药特性及其在小鼠体内的肺靶向性。方法:以聚乳酸为主要辅料,采用溶剂挥发法制备微球,考察其粒径、包封率、载药量,比较微球及原料药的体外释药性;取12只小鼠分别尾静脉注射HCPT微球及原料药,30min后分别测定血浆及各组织的药物浓度并计算相对分布率。结果:所制微球粒径在7～30μm者达81.6%,平均粒径为(14.2±3.1)μm,包封率为72.36%,载药量为(40.6±3.6)%,微球及原料药体外释药参数T50分别为85、18min。微球给药组在肺中的药物浓度最高(32.2±2.48)μg.mL-1,相对分布率58.1%;原料药给药组在血浆中的药物浓度最高(13.52±2.58)μg.mL-1,相对分布率25.24%。结论:所制HCPT微球具有明显的缓释性及肺靶向性。     

肝动脉栓塞米托蒽醌乙基纤维素微球的研究

利用正交实验设计法,优选适用于肝动脉栓塞的米托蒽醌乙基纤维素微球制备条件和工艺;采用动态透析法研究了该微球的体外释药规律;根据混悬液的稳定性理论,优选并制备了适于临床肝动脉介导栓塞使用的米托蒽醌乙基纤维素微球混悬注射液。结果表明∶在优化工艺条件下制得的米托蒽醌乙基纤维素微球外形圆整,球径在40～200μm范围内的占总数的91.9%,平均球径为110.24±38.19μm;包封率为55.6%;载药量为12.5%;体外释药符合单指数模型,释药方程为lg(Y_∞-Y)=-0.116t-1.198×10^-3(γ=0.9992,t₅₀=2.6h);其混悬液适于临床应用。用狗进行的实验表明肝血药浓度高,平均驻留时间比注射剂长2.45倍。     

肺靶向卡铂囊泡的研究

目的制备卡铂非离子型表面活性剂囊泡,以提高卡铂对肺癌的疗效并降低其毒副作用。方法用薄膜分散法制备卡铂囊泡,紫外分光光度法测定药物的含量,二阶导数法测定体外释药。小鼠体内分布试验,用iv.S-180肿瘤细胞建立了肺肿瘤模型,计算瘤结节数。结果卡铂囊泡平均粒径为3.72μm,最小粒径为2.0μm,最大粒径为10.0μm,跨距为0.66。卡铂囊泡包封率为29.2%。体外释药符合双指数方程的规律,释药T_1/2比原药延长9.14倍。体内分布研究表明,卡铂囊泡与原药相比,有明显的肺靶向性。卡铂泡囊对小鼠肺脏S-180肿瘤生长较原药的抑瘤作用有明显提高。结论卡铂囊泡在体内有良好的肺靶向性。     

关节腔内注射用氟比洛芬明胶微球

目的:制备关节腔注射用氟比洛芬明胶微球。方法:按均匀设计法筛选乳化冻凝法制备氟比洛芬明胶微球(FP GMS)的最佳制备工艺。结果:微球粒径范围为2.5～12.3μm,平均粒径为7.53μm,氟比洛芬含量为5.02%(w/w)。其体外释药符合Higuchi方程,稳定性实验表明,FP-GMS的稳定性良好,兔关节腔内注射后,与溶液剂对照组相比氟比洛芬体内平均驻留时间(MRT)显著延长(P<0.01),峰时比对照组延长2.03倍,峰浓度比对照组减小5.57倍。体内外相关性研究表明,FP-GMS体外累积溶出百分率与兔体内药物吸收分数呈显著相关(P<0.01)。结论:本法制备的氟比洛芬明胶微球粒径分布集中,粒径大小符合设计要求,体内外释药结果表明氟比洛芬明胶微球具有明显的缓释作用。     

异烟肼肺靶向性微球的制备及其小鼠体内分布

目的：制备异烟肼肺靶向性微球,评价其体外释药特性及在动物体内的肺靶向性。方法：采用溶剂挥发法制备微球,动态透析法考察其体外释药性能,实验动物静脉注射后测定其各组织的药物浓度,研究其体内相对分布百分率及肺靶向性。结果：制得的微球粒径在7～30μm的占微球总数的88．8％,平均粒径为（16.7±4．6）μm,包封率为86．92％,载药量为（40．7±3.6）％（n=5）,体外释药T50为68min,轻对照组延长了4.5倍。动物实验表明,制得微球后,药物在肺内的相对分布百分率明显高于其它组织与血液,并轻对照组提高了4倍。结论：本法制得的异烟肼微球具有明显的缓释性及肺靶向性。     

甲睾酮聚乳酸微球的制备及其释药性能研究

目的制备甲睾酮聚乳酸微球,研究其体外释药过程。方法采用乳化-溶剂挥发法制备甲睾酮聚乳酸微球;以0.25%SDS-5%乙醇(pH3.4)为释放介质,采用高效液相色谱法测定甲睾酮聚乳酸微球的体外释药量。结果甲睾酮聚乳酸微球开始释药较快,存在一定突释效应,随后以缓慢的方式释药,可用双相动力学方程100-R=35.77e0.1321t+63.91e7.372E-4t描述。结论制成的甲睾酮聚乳酸微球具有明显的缓释作用。     

聚乳酸的降解性能及其微球剂的研究

目的 :研究聚乳酸的降解性能和制备聚乳酸红霉素微球。方法 :将聚乳酸薄膜置于模拟体液中水解 ,用正交设计优选微球制备工艺。结果 :分子量高的降解比分子量低的慢 ,消旋聚乳酸的降解比左旋聚乳酸的快。微球形态圆整 ,性质稳定 ,平均粒径为(10 98±0 15) μm ,体外释药符合Higuchi方程 (Q=28 067 +3 8515T1/2,r=0 9834)。结论 :聚乳酸的降解与分子量和构型有关 ,微球具有明显的缓释作用和满足肺靶向药物的要求     

Characteristic and controlled release of anticancer drug loaded poly (D,L-lactide) microparticles prepared by spray drying technique.

Anticancer drug release from polylactic acid microspheres prepared by the spray-drying process was studied. Several process parameters and properties of the polymer solution have been investigated. Normal size distributions with diameters ranging from 5-10 microm were obtained by the spray drying technique. The yield of microspheres recovered depended on polymer solution and process conditions employed. Results show that the yield of microspheres could reach 50%, and the experimental drug loading approached the theoretical drug loading. Scanning electron microscopy indicated that microspheres were composed of a dense thin skin layer and porous core. The magnitude of this effect depended on the inlet temperature, feed polymer concentration and air flow rate. Increasing inlet temperature and polymer concentration resulted in an intact particle shape and a slower drug dissolution rate. The in-vitro release of anticancer drug from microspheres was sustained over 7 days. The drug release behaviour depended on inlet temperature, air flow rate, PLA concentration and drug loading. The anticancer drug release rate from polylactic acid microspheres prepared by the spray-drying method was depressed, and the long-acting release could be achieved by appropriate operating parameters.     

Characteristic and controlled release of anticancer drug loaded poly (D,L-lactide) microparticles prepared by spray drying technique

Anticancer drug release from polylactic acid microspheres prepared by the spray-drying process was studied. Several process parameters and properties of the polymer solution have been investigated. Normal size distributions with diameters ranging from 5-10 #119 m were obtained by the spray drying technique. The yield of microspheres recovered depended on polymer solution and process conditions employed. Results show that the yield of microspheres could reach 50%, and the experimental drug loading approached the theoretical drug loading. Scanning electron microscopy indicated that microspheres were composed of a dense thin skin layer and porous core. The magnitude of this effect depended on the inlet temperature, feed polymer concentration and airflow rate. Increasing inlet temperature and polymer concentration resulted in an intact particle shape and a slower drug dissolution rate. The in-vitro release of anticancer drug from microspheres was sustained over 7 days. The drug release behaviour depended on inlet temperature, air flow rate, PLA concentration and drug loading. The anticancer drug release rate from polylactic acid microspheres prepared by the spray-drying method was depressed, and the long-acting release could be achieved by appropriate operating parameters.     

肺靶向利福平聚乳酸微球的体外释药性能

本文以０．９％氯化钠的水溶液为释放介质，对利福平聚乳酸微球的体外释药进行了研究。结果表明，微球在最初１０ｍｉｎ有突释效应，此后累积释药量与时间平方根之间呈线性关系。分别考察了微球大小、聚乳酸浓度、微球含药量、制备微球时在甘油中的分散时间和在明胶水溶液中的扩散时间等因素对微球释药性能的影响。     

骨载异烟肼缓释微球的制备及其在动物模型中的释放研究

目的：观察探讨骨载异烟肼聚乳酸微球的设计和制备方法及其在动物模型中的释放效果。方法：选择24只雄性新西兰大白兔作为实验动物模型,采用复乳法制备缓释微球,对微球进行形态学观察、粒径分布观察、体内释药和体外释药观察。结果：平均微球粒径（10.59±0.3）μm,平均包封率（44.9±0.9）%,平均载药率（13.0±0.6）%。在24h、72h、1w、3w微球组滑膜药物浓度明显高于口服组和原药组,P＜0.05。与口服组和原药组对比,微球组0～24h药物波动差值明显更低,P＜0.05。结论：本研究制备的骨载异烟肼缓释微球具有良好的缓释性,能够在抗结核治疗中置入骨结核病灶对术后病灶发挥持久的疗效。     

局部应用环孢素A聚乳酸微球的性状及释药研究

目的对局部应用环孢素A聚乳酸微球的性状及其在体外、体内释放进行研究。方法通过采用O/W型乳化-溶剂挥发法制备环孢素A聚乳酸微球。观察微球分散度、粒径及外观形态及体外释药特性,对比全身与局部给药后全血中及气管组织中的环孢素A药物浓度。结果环孢素A聚乳酸微球的形态圆整,平均粒径18.234μm,跨距:1.131,粒径在9.525～32.400μm者占总数的80%以上。包封率为(86.1±0.8)%,载药量为(34.5±0.6)%。环孢素A聚乳酸微球的体外释药情况:30d的累积释药量为40.8%,采用局部埋植微球后前2周可以维持较高的血药浓度,2周后也可以维持在200ng/ml的药物浓度。结论环孢素A聚乳酸微球具有较好的缓释性能。局部应用可获得有效的血药浓度,在局部气管组织中的药物浓度高于全身用药组。     

5-Fluorouracil-loaded chitosan coated polylactic acid microspheres as biodegradable drug carriers for cerebral tumours

The development of injectable microspheres for anticancer drug delivery into the brain is a major challenge. The possibility of entrapping 5-fluorouracil (5-FU) in chitosan coated monodisperse biodegradable microspheres with a mean diameter of 10-25 um was demonstrated. An emulsion of 5-FU (in water) and polylactic acid (PLA) dissolved in acetone-dichloromethane mixture was poured into an aqueous solution of chitosan (or poly-vinyl alcohol) with stirring using a high-speed homogenizer, for the formation of microspheres. 5-FU recovery in microspheres ranged from 44-66% depending on the polymer and emulsification systems used for the preparation. Scanning electron microscopy revealed that the chitosan coated microspheres had less surface micropores compared to PVA based preparations. The drug release behaviour from microspheres suspended in phosphate buffered saline exhibited a biphasic pattern. The amount of drug release was much higher initially (approximately 25%), followed by a constant slow release profile for a 30 days period of study. This chitosan coated PLA/PLGA microsphere formulation may have potential for the targeted delivery of 5-FU to treat cerebral tumours.     

Cefquinome-loaded microsphere formulations against Klebsiella pneumonia infection during experimental infections

The aim of this study was to prepare cefquinome-loaded polylactic acid microspheres and to evaluate their in vitro and in vivo characteristics and pharmacodynamics for the therapy of pneumonia in a rat model. Microspheres were prepared using a 0.7?mm two-fluid nozzle spray drier in one step resulting in spherical and smooth microspheres of uniform size (9.8?±?3.6?μm). The encapsulation efficiency and drug loading of cefquinome were 91.6?±?2.6% and 18.7?±?1.2%, respectively. In vitro release of cefquinome from the microspheres was sustained for 36?h. Cefquinome-loaded polylactic acid microspheres as a drug delivery system was successful for clearing experimental Klebsiella pneumonia lung infections. A decrease in inflammatory cells and an inhibition of inflammatory cytokines TNF-α, IL-1β and IL-8 after microspheres treatment was found. Changes in cytokine levels and types are secondary manifestations of drug bactericidal effects. Rats were considered to be microbiologically cured because the bacterial load was less than 100 CFU/g. These results also indicated that the spray-drying method of loading therapeutic drug into polylactic acid microspheres is a straightforward and safe method for lung-targeting therapy in animals.     

~(60)Co辐照灭菌对NAO-PLA微球理化特性及体外释放的影响

以 DL-聚乳酸(PLA)为囊材,醋炔诺酮肟(NAO)为主药的微球,可望作为长效避孕注射剂。由于 PLA 的玻璃化温度(T_g)较低,该微球不能采用一般的加热灭菌方法。本文采用10和25kGy 的两种~(60)Co辐照剂量对微球灭菌。对灭菌效果、NAO 和 PLA 以及微球灭菌前后的理化特性和体外释药速率等的比较,表明辐照剂量以10kGy 为宜。