磁性壳聚糖微球的释药和靶向研究

目的：利用改变pH值法制备磁性壳聚糖微球,并对微球的载药量、缓释特性和磁靶向特性进行测试.方法：采用紫外光谱吸收法测定载药量,渗透袋扩散技术测试微球的释药速度,体外模拟法测定微球的磁靶向性.结果：载药量为37%,包封率62%.微球10h内药物释放约为75%,连续释放78h.外加磁场应在2000～3000Gs左右,施加时间在2h为宜.结论：使用改变pH值法制备的壳聚糖微球,具有较高的载药量和包封率,微球缓释效果明显,并实验测出了适合微球靶向控制的磁场施加方式.     

肺靶向多西紫杉醇壳聚糖微球的制备与工艺优化

目的：研制肺靶向多西紫杉醇壳聚糖微球,并对处方工艺进行筛选。方法：以壳聚糖为载体,采用乳化-化学交联法制备多西紫杉醇壳聚糖微球。在单因素考察的基础上,利用正交试验设计优化微球制备工艺,采用HPLC法测定微球的载药量与包封产率。结果：制得的微球显微观察形态圆整、表面光滑,无粘连;平均粒径为（8．63±0．27）μm,粒径7—12μm的微球平均占总数的83．5％,载药量为（25．01±1．80）％,包封产率为（85．54±2．21）％。结论：筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求;该制剂有可能成为临床肺部肿瘤治疗的一种靶向制剂。     

紫杉醇壳聚糖肺靶向微球的制备

目的研制具有肺靶向性的紫杉醇壳聚糖微球,并对处方工艺进行优化。方法以壳聚糖为载体,采用乳化一化学交联法制备紫杉醇壳聚糖微球。单因素试验考察了油／水体积比、紫杉醇浓度、乳化时间、乳化剂量等因素,采用正交设计优化微球制备工艺,以HPLC法测定微球载药量、包封率。结果制得的微球显微观察形态圆整、表面光滑,无黏连;平均粒径为（8．23±0．25）μm,粒径在7～12μm平均占微球总数的84．2％,载药量为16．20％±1．15％,包封率为81．29％±1．62％。结论筛选的最佳处方工艺制备的微球粒径大小适宜,可满足肺靶向微球的要求并免除过敏试剂的加入。     

肺靶向贝母素甲明胶微球的制备

目的制备肺靶向贝母素甲明胶微球,并对其理化性质进行考察。方法采用乳化—化学交联法制备贝母素甲明胶微球;采用光学显微镜对微球形态、粒度分布等进行考察;利用柱前衍生HPLC方法测微球的包封率和载药量;利用透析法考察微球体外释药特性。结果在光学显微镜下观察,微球呈球形,表面光滑,很少黏连,平均粒径10.72μm,粒径在5～25μm范围内的微球占总数的85.8%,载药量为5.128%,包封率为66.35%,体外释药具有缓释特征。结论微球的粒径、形态、载药量和包封率、体外释药性能等基本符合肺部靶向的要求。     

依托泊苷肺靶向壳聚糖微球的研制

目的:制备难溶性药物依托泊苷肺靶向壳聚糖微球,并对处方工艺进行筛选.方法:以壳聚糖为分散介质,采用乳化交联法制备依托泊苷肺靶向壳聚糖微球.结果:平均粒径为13.28μm,载药量为25.30%,药物包封率为43.51%.结论:制备的微球具有良好的缓释作用和靶向性.     

丝裂霉素C磁性纳米微球的制备

目的:以丝裂霉素C为药物模型,研究磁性纳米抗肿瘤药物的制备工艺及方法。方法:采用正交设计优化工艺并筛选,以纳米级Fe_3O_4为磁性核心,人血清白蛋白为膜材,利用乳液固化法制备包载丝裂霉素C 的磁性纳米微球,并借助透射、扫描电镜观察微球形态,通过激光粒度分析仪作粒度分析,利用高效液相色谱(HPLC)测量载药量及包封率,以磁性测试仪进行体外磁响应性测定。结果:该优化的磁性纳米微球在电镜下呈表面光滑的核壳样球型微粒,平均粒径为217.7nm,微球载药量为7.89%,包封率为90.5%,体外饱和磁化强度为21.85emu·g~(-1)。结论:磁性纳米载药微球为肿瘤的主动靶向治疗提供了一种可能的新剂型,有较好的临床应用前景。     

利福平丝素蛋白载药微球的制备及性能研究

目的通过测定利福平丝素蛋白微球的载药量、包封率及释放度,考察乳化转速、有机溶剂与丝素蛋白溶液比例,对微球的制备方法进行优化,筛选微球的最佳制备方法。方法采用乳化法制备利福平丝素蛋白微球,以不同转速、有机溶剂与丝素蛋白溶液不同比例分别制备利福平丝素蛋白微球,采用扫描电镜观察微球的形态,用紫外分光光度法测定微球的载药量、包封率及释放度,以形态、载药量、包封率及释放度为指标,筛选微球的最佳制备方法。在此基础上,采用最佳处方制备3批利福平丝素蛋白微球,对微球的形态、粒径、包封率、载药量和释放度进行考察。结果有机溶剂与丝素蛋白溶液体积比为4∶1、转速为200 r·min^-1时所得利福平丝素微球形态均匀,近似球形,载药量和包封率较高,所得载药微球有较好的缓释作用。以最佳处方制得微球载药量为66.1%±0.87%,包封率为87.80%±2.23%。结论有机溶剂与丝素蛋白溶液体积比为4∶1、转速为200 r·min^-1时载药量、包封率和释放度较好,故选择此处方为利福平丝素蛋白微球的最佳制备处方。     

肺靶向硫酸链霉素明胶微球的制备

目的:用生物可降解材料明胶制备肺靶向硫酸链霉素明胶微球.方法:用乳化法制备微球,正交试验设计考察影响制备工艺的因素,用扫描电子显微镜观察微球表面形态,用红外光谱分析确证含药微球的形成.并对所制备的硫酸链霉素明胶微球的粒径及其分布、载药量、包封率、稳定性等进行了研究.结果:微球形态圆整,药物确己存于微球中.微球的平均粒径为12.269 μm,粒径在5.0～25.0 μm的微球占总数的91.5%,达到肺靶向要求.载药量为42.6%,包封率为53.8%.最佳工艺条件重现性好.经37℃、RH75%放置3个月,其含量、外观形态及大小基本不变.结论:该微球制备工艺稳定,可用于肺靶向注射剂的研究.     

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。     

甲氨蝶呤叶酸受体-磁双重靶向纳米粒的制备及评价

目的：以甲氨蝶呤为药物模型，制备用于肿瘤靶向治疗的叶酸受体-磁双重靶向纳米药物。方法：未采用 预成型的磁性纳米粒，一步合成磁性纳米粒核二氧化硅壳超顺磁性的纳米粒，并借助透射、扫描电镜观察微球形态，用 硅烷偶联剂进行表面修饰，在表面化学偶联上叶酸，修饰甲氨蝶呤后利用紫外可见分光光度计测量载药量及包封率。结 果：磁性纳米粒在电镜下呈现核壳样球型微粒，平均粒径为20 nm，纳米粒载药量为26.71%，包封率为64.76%。结论： 叶酸受体-磁双重载药纳米粒为肿瘤的靶向治疗提供了一种可能的新剂型，有较好的临床应用前景。     

多西紫杉醇微球的质量评价

目的:考察多西紫杉醇微球的质量。方法:应用高效液相色谱(HPLC)分析方法,测定多西紫杉醇微球载药量、包封率,并进行体外释放特性的研究,考察其形态和粒度分布。结果:在设定的色谱条件下,多西紫杉醇与辅料及溶剂峰分离良好,在1~40mg/L浓度范围内,线性关系良好(r=0.9998,n=5);微球呈球形,圆整、表面光滑,平均粒径26.9μm,包封率81.56%,载药量16.32%;体外释放试验表明,其制剂96h体外累积释药百分率为64.44%。结论:该法分析多西紫杉醇微球质量,方法可靠;其微球粒度分布窄,包封率高、缓释作用明显。     

糖类交联明胶微球的制备及其释药特性研究

目的:以生物相容性的糖作交联剂制备明胶药物载体并研究其释药特性。方法:用葡萄糖、葡聚糖、氧化葡萄糖、氧化葡聚糖作交联剂制备明胶盘和微球,测定其溶胀动力学,分别以阿司匹林和牛血清白蛋白为药物模型,紫外分光光度法测定药物包裹率、载药率,并检测明胶微球在模拟体内条件下药物的释放速率。结果:葡萄糖、氧化葡萄糖、葡聚糖、氧化葡聚糖作交联剂制备的凝胶溶胀率分别为204%、246%、166%、233%;4种阿司匹林和牛血清白蛋白明胶微球平均载药率分别为8.73%和4.05%,平均包封率分别为62.55%和31.40%;2h药物释放百分率依次为30%、14%、76%、73%和97.2%、86.6%、60.8%、50.1%。结论:上述4种糖均可以取代化学交联剂制备明胶微球;天然糖交联微球缓释效果优于氧化糖。     

槲皮素包合物微球的制备及其体外释放研究

目的:制备槲皮素β-环糊精包合物-壳聚糖微球(QT-CD-CM),并考察其理化性质和药物体外释放性能。方法:采用有机溶剂挥发法制备槲皮素β-环糊精包合物,再用乳化分散-离子交联法、以三聚磷酸钠为交联剂制备壳聚糖微球,并考察其形态、粒径、包封率、载药量和体外释放情况。结果:制备的QT-CD-CM形态规则、均质、无粘连,平均粒径(3.327±0.124)μm,包封率为32.4%,载药量为12.3%,在5%乙醇-磷酸盐缓冲液介质中72h可以达到完全释药,释药过程符合一级动力学模型。结论:QT-CD-CM理化性质及体外释药性能良好,制备工艺简单,有望成为理想的槲皮素给药系统。     

布洛芬微球的制备及影响因素考察

目的研究乳化溶剂扩散法制备布洛芬微球的工艺。方法采用乳化溶剂扩散法制备布洛芬微球,以粒度分布、载药量以及包封率为指标,对处方及工艺进行单因素考察,选出较佳的处方和工艺条件,并对所得微球的外观及体外释放度进行研究。结果该法所制微球外观圆整,流动性好,粒径分布集中在2~20μm,包封率为69.74%,载药量为68.37%。结论布洛芬微球的制备工艺简单,所制微球粒径小,分布窄。体外释药试验表明所得布洛芬微球在人工肠液中有明显的缓释作用。     

PLGA微球的制备及其用于脉冲给药的初步研究

目的：制备聚乳酸-羟基乙酸共聚物（PLGA）微球,并考察其用于脉冲式释药系统的可行性。方法：以牛血清白蛋白（BSA）为模型药物,用S/O/W（Solid-in-oil-in-water）法和S/O/O（Solid-in-oil-in-oil）法制备PLGA（75：25）和PLGA（50：50）微球,比较2种方法制备的微球的表面形态、包封率及载药量等,并考察2种微球的体外释放行为。结果：S/O/W法和S/O/O法制备的微球均圆整、无粘连、形态良好,但S/O/W法制备的微球表面较为平整,而S/O/O法表面均匀分布有较大的凹陷。S/O/W法制备的PLGA（75：25）和PLGA（50：50）微球包封率分别为（60.15±5.95）%、（49.50±3.69）%,载药量分别为（2.56±0.25）%、（2.10±0.16）%,10h内药物释放均为10%左右,而后随着聚合物的降解药物的释放量突然增加;S/O/O法所制微球包封率分别为（84.36±1.11）%、（77.94±1.42）%,载药量分别为（3.58±0.05）%、（3.31±0.06）%,24h内药物释放均可达50%左右,而后呈现较为平稳的释放行为。S/O/O法制备的微球包封率及载药量均较S/O/W法高;S/O/W法制备的PLGA微球药物释放呈现一定的脉冲行为,其中PLGA（75：25）微球体外释放行为受微球粒径的影响较大。结论：S/O/W法制备的PLGA微球具有一定的脉冲式释药效果,微球的粒径最好控制在120μm以下。     

正交试验优选α-细辛脑明胶微球制备工艺

目的:优选α-细辛脑明胶微球的制备工艺。方法:采用乳化缩聚法制备α-细辛脑明胶微球,以明胶浓度、乳化剂用量、搅拌速度、投料比为考察因素,以载药量和包封率的综合评分为评价指标,采用正交试验优化工艺,并观察微球形态、粒径分布。结果:最优工艺为明胶浓度20%、乳化剂用量3.0mL、搅拌速度800r·min-1、投料比1∶2;所制得的微球球形圆整,平均载药量为3.98%,平均包封率为24.25%。结论:所选工艺稳定,各项质量指标良好。     

Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres

Etanidazole, a hypoxic radiosensitizer, has potential applications in radiotherapy. Due to its high solubility in water, common methods to encapsulate etanidazole into microspheres are not feasible. In this study, a spray-drying technique was employed to encapsulate etanidazole into the biodegradable polymer, PLGA65:35. Different fabrication conditions, such as polymer concentration, inlet temperature, feed rate, compressed air flow rate, aspirator ratio, as well as drug-loading were investigated to understand their effects on the particle size and distribution, encapsulation efficiency, and release behaviour. The effect on the morphologies of microspheres were also observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was demonstrated that most of these fabrication conditions influence either the droplet formation process or its subsequent evaporation and particle shrinking process, thereby determining the properties of the microspheres obtained. In many cases, temperature seems to be more important among all the factors considered. The present study demonstrates good fabrication conditions for producing the etanidazole-PLGA65:35-microspheres by using DCM as a solvent. The release of etanidazole from the spray dried PLGA65:35 microspheres was very fast, with an initial burst of 47% within the first 30 min and a cumulative release of over 80% within the first 5.5 h. The encapsulation efficiency of the drug in the microspheres varied with operating conditions from 69-96%.     

Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres

Etanidazole, a hypoxic radiosensitizer, has potential applications in radiotherapy. Due to its high solubility in water, common methods to encapsulate etanidazole into microspheres are not feasible. In this study, a spray-drying technique was employed to encapsulate etanidazole into the biodegradeable polymer, PLGA65:35. Different fabrication conditions, such as polymer concentration, inlet temperature, feed rate, compressed air flow rate, aspirator ratio, as well as drug-loading were investigated to understand their effects on the particle size and distribution, encapsulation efficiency, and release behaviour. The effect on the morphologies of microspheres were also observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was demonstrated that most of these fabrication conditions influence either the droplet formation process or its subsequent evaporation and particle shrinking process, thereby determining the properties of the microspheres obtained. In many cases, temperature seems to be more important among all the factors considered. The present study demonstrates good fabrication conditions for producing the etanidazole-PLGA65:35-microspheres by using DCM as a solvent. The release of etanidazole from the spray dried PLGA65:35 microspheres was very fast, with an initial burst of 47% within the first 30 min and a cumulative release of over 80% within the first 5.5 h. The encapsulation efficiency of the drug in the microspheres varied with operating conditions from 69-96%.     

Paclitaxel loaded poly(L-lactic acid) (PLLA) microspheres. II. The effect of processing parameters on microsphere morphology and drug release kinetics

The kinetics of solvent removal in microsphere preparation and their effect on the morphology and release characteristics of paclitaxel-loaded PLLA microspheres were determined. Microspheres were analyzed by SEM and DSC and in vitro paclitaxel release was monitored by HPLC. During manufacture, dichloromethane evaporated at a constant rate, which increased with dispersion stirring speed and decreased with increasing paclitaxel content. Paclitaxel-loaded microspheres had a dimpled surface, due to surface deposition of the drug, while controls were smooth. In the formation of larger microspheres, the deposition of drug in the surface slowed the solidification process resulting in drug-loading dependent thermal properties. Paclitaxel release did not follow diffusion kinetics, rather it was characterized by a large burst followed by a linear phase. We speculate that non-uniform (surface-rich) drug distribution in the microspheres may contribute to the deviation from the theoretical pattern of kinetics for diffusion from a sphere.     

正交试验优选姜黄素明胶微球的处方工艺

目的:优选姜黄素明胶微球的最佳处方工艺。方法:以明胶浓度、油水比例、乳化时间为考察因素,以载药量、包封率、微球粒径为评价指标,以明胶为载体,采用正交试验优选乳化交联法制备姜黄素明胶微球的处方工艺。结果:优选的处方工艺要求油水比为1:5,明胶浓度为25%,乳化时间为30min。结论:该处方工艺稳定、可行,重现性好,可为姜黄素明胶微球的后续研究提供理论依据。