玻璃体内注射用醋酸地塞米松聚丙交酯缓释微球

目的　研制玻璃体内注射用醋酸地塞米松聚丙交酯微球(DA-PL-MS)及其相关性质,并在家兔玻璃体内注射,观察治疗实验性增殖性玻璃体视网膜病变(PVR)的效果。方法　溶剂挥发 萃取法制备DA-PL-MS ,考察微球的粒径大小与分布、载药量、包封率和体外释放特性,用差示扫描量热分析和X 射线粉末衍射分析鉴别物相,并考察眼内安全性及组织中的分布。观察巨噬细胞造型白化家兔眼,确定玻璃体内注射微球后对PVR的防治效果。结果　微球的平均几何粒径为62.94μm ,跨距为0.92 ,载药量为17.50% ,包封率86.52% ,体外90d释放约90% ,比原药延长约一倍。空球组对治疗PVR无效;原药组对治疗PVR有短期作用,作用时间为42d ;微球组药效持久,84d时眼底仍清晰,无明显增生与牵拉,且未发现明显的刺激性及毒性。结论　DA-PL-MS玻璃体内注射给药有较高的安全性,并可提高防治实验性PVR的效果     

氟尿嘧啶聚丙交酯微球的制备及体外特性

目的：制备缓释１月以上的的氟尿嘧啶（Ｆｕ）聚丙交酯微球。方法：溶剂挥发法制备Ｆｕ聚丙交酯微球,比较外水相Ｆｕ饱和与否,有机相Ｆｕ／聚丙交酯投料比对载药量及包封率的影响。光学及电子显微镜下对微球的外观形态进行考察。并对其体外释放进行初步探讨。结果：制得的微球光滑圆整。Ｆａｕ饱和外水相后可以提高其载药量及包封率。投料经对载药量、微球的粒径和跨距影响不大,包封率随投料比增大而减小,Ｆｕ从聚丙交酯微球中４周时约释放总量的６５％,符合一级动力学,没有明显的突释放应,结论：外水相Ｆｕ饱和后可减少Ｆｕ向外水相的逸失,制得的微球可作为每月１次的给药系统。     

中心多点等距设计法优化醋酸地塞米松聚丙交酯微球的制备工艺

目的：中心多点等距设计法优化醋酸地塞米松聚丙交酯微球的制备工艺,以提高微球性质的可预测性。方法：微球用溶剂挥发/萃取法制备,自变量为外水相聚乙烯醇浓度、有机相聚丙交酯浓度和投药比,以微球收率、载药量、包封率、平均粒径和跨距为因变量对自变量的各水平进行多元线性回归和二项式拟合,因变量面法选取较佳工艺条件并于较优区进行预测分析。结果：载药量和包封率可用线性模型拟合,复相关系数γ²分别为0.986和0.991;载药量、粒径和跨距可用二项式拟合,复相关系数γ²分别为0.998,0.912和0.935,包封率、平均粒径和跨距的预测值与实测值的偏差分别为-4.09%,-5.18%和-8.33%。结论：中心多点等距设计法优化处方与制备工艺有使用方便,预测性良好的特点,值得推广应用。     

紫杉醇聚丙交酯乙交酯共聚物纳米粒的制备与体外评价

目的采用聚丙交酯乙交酯共聚物（PLGA）载体制备紫杉醇（TAX）纳米粒,并进行体外评价。方法采用改良的溶剂扩散法制备TAX PLGA共聚物纳米粒,考察不同乳化剂类型和各工艺因素对纳米粒粒径的影响,通过动态激光粒度分析仪、透射电子显微镜（TEM）、扫描电子显微镜（SEM）、差示扫描量热法（DSC）及X线粉末衍射（XRD）初步研究其载药性质,并研究纳米粒冻干粉的体外释放特性。结果优选出制备工艺为：双十二烷基二甲基溴化铵（DMAB）作为乳化剂,浓度为1%（W/V）,聚合物浓度为1%（W/V）,水相与有机相的体积比例为20：10,均质机转速为16 000 r•min 1,药物浓度为0.1%（W/V）。所得纳米粒外观圆整,平均粒径为99.0 nm,Zeta电位58.3 mV,包封率为56.77%,载药量率为7.10%。TAX纳米粒具有缓释性,体外释放分为两相。DSC及XRD表明TAX被有效地包裹在纳米粒中。结论PLGA纳米粒可成为TAX的新型载体。     

一阶导数光谱法测定聚丙交酯微球中5-氟尿嘧啶或醋酸地塞米松的含量

二氯甲烷-无水乙醇混合溶剂溶解聚丙交酯微球,一阶导数紫外分光光度法测定5-氟尿嘧啶或醋酸地塞米松的含量。以一阶导数光谱5-氟尿嘧啶277nm和醋酸地塞米松266nm波长处的零谷距作为定量指标,线性关系良好,测定方法简便、快捷、准确。     

高效液相法测定聚丙交酯微球中醋酸地塞米松的含量

目的建立高效液相色谱法测定醋酸地塞米松聚丙交酯微球含量测定。方法采用ODS柱(250mm×4.6mm,5μm),流动相为乙腈:25mmol·L-1磷酸盐缓冲液(pH3.0)(45∶55,V/V),检测波长:240nm。结果醋酸地塞米松在5~30μg·mL-1(r=0.9996,n=5)浓度线性关系良好,平均回收率为95.55%,RSD=2.4%。结论本方法操作简便、快速、准确,能很好地定量测定醋酸地塞米松聚丙交酯微球的含量。     

载自杀基因聚丙交酯乙交酯纳米粒的研制

目的 :对载自杀基因聚丙交酯乙交酯纳米粒的制备工艺进行考察 ,并评价其体外质量。方法 :以聚丙交酯乙交酯为载体材料 ,采用复乳溶媒蒸发法制备载 pEGFP TKAFB重组质粒纳米粒 ,并对其形态、包封率、体外释放、抗核酸酶抗超声的能力等进行研究。结果 :纳米粒形态圆整、大小均匀 ,平均粒径为 72nm ,平均包封率为 91.2 5 % ,体外释药速度依赖于载体材料的分子量 ,质粒制成纳米粒后对抗超声剪切及核酸酶降解的能力增强。结论 :本纳米粒制备工艺简单 ,质量可控。     

两种方法制备肺靶向地塞米松磷酸钠微球的比较

目的:研究两种制备方法所制备的肺靶向地塞米松磷酸钠微球的特性,确定两种方法是否适合用于制备该微球。方法:对油／水型乳化-溶剂挥发法的工艺进行优化,以优化后的油／水型乳化-溶剂挥发法和水／油／水型乳化-溶剂挥发法制备微球,考察微球的大小、载药量、体外释药等性质。结果:两法所制的微球的平均粒径相近,载药量和体外释药特性各不相同。结论:两种方法都适合用于制备肺靶向的地塞米松微球。从载药量方面分析,优化后的油／水型乳化-溶剂挥发法较好。     

尼索地平微球的制备

采用溶剂挥发法制备了尼索地平微球 ,考察了制备工艺中影响微球质量的 5个主要因素 ,筛选出较理想的处方和工艺。所得微球形态圆整 ,表面光滑 ,粒径 (18.2± 3.8) μm,载药量 2 1.2 % ,包封率 85 .4 %。     

阿霉素聚乳酸微球的制备及体外释药特性研究

目的:对阿霉素聚乳酸微球的制备工艺、含量测定及体外释药特性进行初步研究.方法:以人工合成可生物降解聚合物聚乳酸为载体,采用乳化-溶剂挥发法制备阿霉素聚乳酸微球,用UV-260紫外分光光度计测定其药物含量和体外释药量.结果:所制备的阿霉素聚乳酸微球外形圆整,算术平均球径为55.2 μm,载药量为30.21 μg*mg-1,12 h体外累积释药量36%.结论:聚乳酸微球具有很好的控释能力,使用前景广阔.     

Preparation and characterization of letrozole-loaded poly(d,l-lactide) nanoparticles for drug delivery in breast cancer therapy

Letrozole (LTZ), an aromatase inhibitor used for the treatment of hormonally-positive breast cancer in postmenopausal women, has poor water solubility, rapid metabolism, and a range of side effects. In this study, polymer-based nanoparticles (NPs) incorporating the drug have been designed and characterized, aimed to control the release, potentially maximize the therapeutic efficiency, and minimize the side effects of the drug. LTZ was incorporated into poly(d,l-lactide) (PDLLA) NPs by employing the emulsion-solvent evaporation technique using a range of drug concentrations. Loaded drug and drug-polymer interactions were studied using X-ray diffraction and NPs morphology was evaluated using scanning electron microscopy (SEM). Particle size distribution (PSD) and zeta potential of the NPs were analyzed using dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), respectively. Drug content and release profile studies were carried out and determined using ultra performance liquid chromatography (UPLC). The yield of LTZ-PDLLA NPs reached as high as 85%. The NPs were spherical and smooth, regardless of LTZ concentration in the formulation. However, particle size increased from 241.6?±?1.2 to 348.7?±?6.1?nm upon increasing LTZ concentration from 0 to 30% w/w, with entrapment efficiencies reaching up to 96.8%. Drug release from the polymeric matrix was best described by Higuchi model with a predominant diffusion-based mechanism. More than 15, 46, and 86% of LTZ was released in a controlled fashion over 30?d from the 10, 20, and 30% LTZ-PDLLA NPs, respectively. Overall, LTZ-PDLLA NPs were designed with appropriate size and surface charge, high drug loading, superior entrapment efficiency, and prolonged release profile.     

Biological Activity of Lysozyme After Entrapment in Poly (d,l-lactide-co-glycolide)-Microspheres

Purpose. The purpose of this study was to investigate the process of preparing microspheres for maximising entrapment efficiency (EE) and retained biological activity (RBA) of peptides and proteins. Methods. A controlled-release formulation based on poly(d,l-lactide-co-glycolide) was designed and produced using a small-scale double emulsion method. These PLG microspheres contained a model peptide, lysozyme. The retained bioactivity of the incorporated lysozyme was determined by bacterial assay. The size distributions and the morphology of the microspheres were characterized. Results. The RBA and EE improved when the PLG concentration in the organic phase of the emulsion was increased. A high lysozyme concentration in the inner water phase of the emulsion resulted in decreased EE and an increase in the proportion of fragmented particles. The RBA of lysozyme in the microspheres varied between 30 and 80% with changes to the process. Conclusions. The study shows that the RBA of lysozyme in PLG microspheres is strongly dependent on the experimental conditions for preparing the microspheres. Measurement of the EE alone, without the RBA is insufficient to evaluate the efficacy of the designed delivery system.     

表面修饰的灯盏花素聚乳酸纳米粒的制备和大鼠体内药动学*

目的:制备灯盏花素聚乳酸纳米粒并对其进行了表面修饰,同时考察了游离药物和纳米药物经大鼠尾静脉注射后在动物体内的药动学。方法:采用自乳化溶剂扩散法制备灯盏花素聚乳酸纳米粒,并用泊洛沙姆188对纳米粒进行表面修饰,采用反相高效液相色谱法(RP-HPLC)测定纳米粒的包封率、载药量和血浆样品中灯盏花素的含量,药时数据采用DASver 1.0药代计算程序处理。结果:载药纳米粒平均粒径为177.2和319.6 nm,多分散指数分别为(0.11±0.01)和(0.12±0.02),平均包封率及载药量分别为(86.9±0.9)%,(8.0±0.2)%和(93.1±0.6)%,(8.5±0.1)%,游离灯盏花素iv后呈二室模型,t1/2β为(0.81±0.14)m in,纳米组则呈一室模型,2种粒径的纳米粒的t1/2β分别为(8.90±0.16)m in(177.2 nm)和(13.90±0.07)m in(319.6 nm)。游离灯盏花素和2种粒径的灯盏花聚乳酸纳米粒的AUC0~t分别为(158.82±69.96),(1 476.25±51.22)和(704.95±25.39)mg.m in.L-1。经t检验,游离药物与纳米药物之间的t1/2β和AUC0~t均有统计学差异(P<0.01)。结论:灯盏花素制成纳米粒后明显增加了药物在动物体内的半衰期,延长了药物在体内的循环时间,且不同粒径的纳米粒对药动学有一定的影响。     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg^?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h^?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.     

Formation and characterization of cisplatin loaded poly(d,l-lactide) microspheres for chemoembolization

Cisplatin, a slightly water soluble anticancer drug, has been incorporated into biodegradable poly(d,l-lactide) microspheres using the solvent evaporation process. The optimal experimental conditions to produce spherical and separate drug-loaded particles (45% cisplatin) were as follows: the dispersing phase was a mixture of 0.05% methylcellulose and 4% polyvinyl alcohol (8 mPa-s grade); and the optimal poly(d,l-lactide) concentration in the organic phase was found to be greater than or equal to 7.16%. Microscopic studies showed that increasing the drug content in the microspheres produced the appearance of rod-like crystals at the microparticle surface. In addition, the cisplatin crystals were found homogeneously distributed in the polymer matrix, even at a high drug content. Increased viscosities of the organic phase enhanced the mean microsphere size, while increasing the emulsifier concentration in the aqueous phase decreased the average particle size. The drug incorporation efficiency was markedly improved after saturation of the dispersing phase with cisplatin. It was also noted that the amount of drug incorporated increased with increasing mean microsphere diameter. The methylene chloride content entrapped within the microspheres was found to depend upon the microsphere size distribution and the cisplatin content. An increase of the microsphere system porosity, by the addition of 10% cyclohexane in the organic phase, caused a reduction in the residual methylene chloride content. Finally, the in vitro release kinetics of cisplatin were influenced by the drug loading.     

Characterization of drug-loaded poly(d,l-lactide) microspheres

Lomustine and progesterone have been incorporated in biodegradable poly(d,l-lactide) microspheres by evaporating dichloromethane from stirred dichloromethane-in-water emulsions. Spherical microspheres with lomustine or progesterone payloads less than or equal to 23% were obtained. Higher lomustine payloads gave irregularly shaped particles. Microspheres with less than or equal to 68% progesterone were obtained, but free drug crystals formed on the surface of such microspheres. Increased agitation rates decreased mean microsphere size. Addition of drug to the dichloromethane phase increased average particle size relative to that obtained with drug-free microspheres prepared under the same experimental conditions. Complete evaporation of the dichloromethane, while the medium was continuously stirred, promoted formation of free drug crystals in the aqueous phase. Increased emulsifier concentrations did not significantly enhance drug incorporation efficiency within the microspheres. Shelf-life stability of lomustine and progesterone was reduced by incorporation in the microspheres, presumably due to their molecular dispersion in the poly(d,l-lactide).     

60Co辐照对睾丸酮/乳酸-乙醇酸共聚物微球理化特性及体外释放的影响

目的 :睾丸酮 (T) /乳酸 -乙醇酸共聚物 (PLGA)微球6 0 Co辐照灭菌可行性研究。方法 :T/PLGA微球在6 0 Co源下 ,以 2 5kGy的剂量进行辐照 ,对微球辐照前后主药T、载体PLGA的理化特性和微球体外释药速率的变化进行比较 ,考察6 0 Co辐照对T/PLGA微球理化特性及药物体外释放的影响。结果 :6 0 Co辐照引起PLGA分子量一定程度的下降 ,但对T/PLGA微球的理化特性及体外释药速率没有影响。结论 :初步的可行性研究表明T/PLGA微球可用6 0 Co辐照灭菌     

The Preparation and Evaluation of Drug-Containing Poly(dl-lactide) Microspheres Formed by the Solvent Evaporation Method

Several compounds such as caffeine, diazepam, hydrocortisone, progesterone, quinidine, quinidine hydrochloride, quinidine sulfate, and theophylline were evaluated for incorporation into poly(dl-lactide) (PLA) microspheres using the solvent evaporation technique. The process is generally limited to the entrapment of water-insoluble drugs. Adjustment of the pH of the aqueous phase to minimize drug solubility resulted in increased drug contents within the microspheres in the case of ionizable drugs. The release profile of quinidine from the microspheres was characterized by three different release phases, a lag time with no drug release, a burst effect of rapid drug release within a short period of time, and a slow release phase, respectively. The structure of the microsphere surface layer, which was a function of the pH of the aqueous phase at preparation, strongly influenced the rate and amount of drug released. Thermal analysis of quinidine-loaded microspheres revealed three thermal events, corresponding to the glass transition temperature of the polymer and to the recrystallization and melting of quinidine.