美洛昔康PLA缓释微球的制备及性能研究

以生物可降解材料聚乳酸(PLA)作为载体,聚乙烯醇为分散剂,二氯甲烷为溶剂,采用乳化-溶剂挥发法制备美洛昔康(Meloxicam)聚乳酸缓释微球。用生物显微镜和扫描电子显微镜观察微球形态,用傅里叶红外光谱仪检测美洛昔康是否已存在于微球中,用紫外-可见分光光度计测定了微球的包封率、载药量及其体外释药特性。结果表明:美洛昔康聚乳酸缓释微球光滑圆整,聚乳酸和美洛昔康能够有机地结合为一体,微球载药量为12.72%,包封率为89.04%,美洛昔康/PLA微球体外释放80 h后累积释药率达70%以上,具有显著的缓释作用。     

聚乳酸载药微球形成机理的模拟分析与实验研究

对聚乳酸载药微球的形成过程进行了耗散颗粒动力学模拟和实验研究。载药体系以硝苯地平为模型药物、聚乳酸（poly-lactic acid, PLA）为载体材料、聚乙烯醇（poly vinyl alcohol, PVA）为稳定剂。通过研究,提出了聚乳酸载药微球的形成机理,认为微球形成过程可分为4个阶段,即高度分散阶段、PLA分子聚集阶段、硝苯地平分子向微球内部扩散阶段和微球的形成及稳定阶段。机理分析和模拟表明,微球对硝苯地平的包载量有一个临界值,硝苯地平浓度低于该值,几乎所有的硝苯地平分子都能扩散进微球的内部;高于该值,则部分硝苯地平分子难以扩散进微球内部,而分散在介质中,形成硝苯地平聚集体。     

静电喷雾法制备聚乳酸/布洛芬微球及其性能研究

采用静电喷雾技术,以聚乳酸（PLA）为骨架载体材料,布洛芬（IBU）为模型药物,成功制备出PLA载IBU微球,利用扫描电子显微镜（SEM）、X射线衍射仪（XRD）、差示扫描量热仪（DSC）、傅里叶变换红外光谱仪（FTIR）、热失重分析仪（TG）和紫外可见分光光度计分析了微球形貌、结构和性能。结果表明,PLA/IBU微球呈表面多孔的无定形结构,分散性较好,IBU以分子或无规则状态负载在PLA中,化学结构未有变化,稳定性较纯IBU有所提高。在体外缓释测试中,PLA/IBU微球相比较纯IBU具有良好的缓释效果,随着投药量的增加,IBU的释放速率和累计释放量逐渐提高,含16 %IBU的PLA微球在48 h内累计释放量可达52 %。静电喷雾法制备的PLA/IBU微球有望提高IBU的生物利用度和溶出率,在生物医药领域具有潜在的应用前景。     

硝苯地平聚乳酸缓释微球的制备

采用溶剂蒸发法,以聚乳酸为载体、二氯甲烷为溶剂、聚乙烯醇为分散剂制备了具有缓释功能的硝苯地平微球。研究结果表明微球粒径随搅拌速度的提高而减小;当聚乳酸用量一定时,溶剂体积增大,微球的粒径减小。扫描电子显微镜观察微球的外观为一光滑的圆球,平均粒径为18.9μm。释放研究表明载药微球具有控释功能,释放时间长达50h。     

可降解聚乳酸多孔微球的制备探究

以聚乳酸为壁材,碳酸氢铵为致孔剂,采用双乳液溶剂挥发法,制备出具有孔状的聚乳酸微球,探讨制备条件对聚乳酸微球的影响.结果表明,在内外水相体积比1∶7.5,初乳化搅拌速度1 000 r/min下制得的PLA多孔微球的球形和孔结构较好.     

聚乳酸/羟基磷灰石微球的合成与性能

以生物可降解高分子材料聚乳酸(PLA)为载体,羟基磷灰石(HA)为核心材料,采用溶剂蒸发法制备了聚乳酸/羟基磷灰石(PLA/HA)微球。在可确定因素固定下来后,在保证成球质量的基础上,分别通过调节乳化剂浓度和其它因素在一定范围内控制微球的平均粒径。通过正交实验摸索出制得粒径大小为200μm左右PLA/HA微球的最佳工艺方案:搅拌速度为500r.min-1,PLA浓度为0.08g.mL-1,PVA浓度为0.006g.mL-1,HA添加量为0.10g。扫描电镜(SEM)表明微球外观基本光滑圆整,但表面有少许小孔和凹槽;观察了PLA/HA微球在生理盐水中的降解行为,发现其降解速率低于纯聚乳酸;通过对微球释药率的研究发现其具有良好的缓释性能。     

聚乳酸/磷酸三钙微球的合成与性能

以生物可降解高分子材料聚乳酸(PLA)为载体,磷酸三钙(TCP)为核心材料,采用溶剂蒸发法制备了聚乳酸/磷酸三钙(PLA/TCP)微球。在可确定因素固定下来后,在保证成球质量的基础上,分别通过调节乳化剂浓度和其他因素在一定范围内来控制微球的平均粒径。单因素实验结果表明:搅拌速度,PLA浓度,PVA浓度,油水相体积比这4个因素对微球性能影响显著。通过正交实验摸索出制得粒径大小为200μm左右PLA/TCP微球的最佳工艺方案:即搅拌速度为600r/min,PLA质量浓度为0.07g/mL,PVA质量浓度为0.005g/mL,油水相体积比为10/50(mL/mL)。激光粒度分析仪数据分析表明搅拌速度越快微球分布越均匀;用电镜观察微球的形态,微球圆整无粘连;通过测量缓冲液pH值的变化研究其降解规律和机制;研究微球释药率发现其具有良好的缓释性能。     

聚乳酸/纳米四氧化三铁载阿奇霉素缓释剂的制备及性能研究

采用乳化-溶剂挥发法,以可生物降解材料聚乳酸为载体,在其中加入医药级阿奇霉素和一定量纳米四氧化三铁制备聚乳酸/纳米四氧化三铁载阿奇霉素缓释微球,通过正交实验优化了制备工艺,并研究了微球的释药行为.结果表明,微球具有明显的药物缓释作用.     

载柚皮素聚乳酸微球的制备、表征及释药性能研究

采用改良的溶剂挥发法,将柚皮素制备成载柚皮素聚乳酸微球;并采用扫描电镜(SEM)、红外光谱(IR)、动态光散射粒度仪(DLS)、紫外可见分光光度计对微球的形貌、组成、载药性能和缓释性能等进行了表征测试。结果表明,优化工艺制得的载药微球呈圆整球形,粒径分布均匀,分布在100~200 nm之间,载药量为22.3%,包封率为64.7%,且在人工模拟体外环境下具有良好的缓释效果。该载药聚乳酸微球有望提高柚皮素的生物可利用度和溶解性,在生物医药领域具有潜在的应用前景。     

DSP-PELA/SiO2微球的制备及其体外释药研究

采用自制的聚乳酸-聚乙二醇-聚乳酸/SiO2 PELA/SiO2)材料作为药物载体,通过溶剂挥发法制备了地塞米松磷酸钠(DSP)微球,并对微球的粒径、载药量以及体外缓释性能进行了研究.微球电镜图片显示其粒径大小分布在8μm左右,符合缓释制剂要求.体外缓释研究结果显示,PELMSiO2微球具有明显的缓释作用.     

Preparation and characterization of nifedipine-loaded cellulose acetate butyrate based microspheres and their controlled release behavior

Eudragit L100/cellulose acetate butyrate blend microspheres were prepared by solvent evaporation technique using poly(vinyl alcohol) as an emulsifying agent nifedipine (NFD) was successfully loaded into these microspheres. The effect of experimental variables such as ratio of blend ratio on NFD encapsulation efficiency, release rate, size, and morphology of the microspheres has been investigated. Scanning electron micrographs indicated the formation of spherical microspheres. Mean particle size of the microspheres has been measured by the laser light scattering technique ranged between 100 and 120 μm. NFD was successfully encapsulated up to 80% in the polymeric matrices. In vitro dissolution experiments performed in pH 7.4 buffer medium indicated a controlled release of NFD from the blend microspheres up to 12 h.     

聚乳酸微球的制备

以L-乳酸为原料,锡粒为催化剂,实现了丙交酯的开环聚合反应,红外光谱结果表明,合成了分子量可控的聚乳酸。以二氯甲烷为溶剂,聚乙烯醇为表面活性剂,制备了聚乳酸微球,研究了聚乙烯醇浓度对聚乳酸微球的影响。结果表明,当聚乙烯醇浓度增加时,微球半径变小,但粒径分布均匀度下降,聚乙烯醇浓度为1%时,聚乳酸成球效果较好。     

Protein encapsulation in biodegradable amphiphilic microspheres. I. Polymer synthesis and characterization and microsphere elaboration

Polymerization of lactide on monomethoxypolyoxyethylene (MPOE), using stannous octoate as a catalyst, was carried out in bulk and in solvent. Polymerization in a solvent permits one to work at a lower temperature and thus to prevent transesterification reactions. The copolymers synthesized in solvent exhibited a lower polydispersity and a polylactic acid (PLA) block longer and closer to the expected one. Therefore, this procedure was used to synthesize a series of diblock copolymers MPOE–D ,L -PLA, keeping the PLA chain constant (45,000 g/mol), the MPOE block increasing from 2000 to 5000, 10,000, 15,000, and 20,000 g/mol. The longer the MPOE chain, the higher the water uptake in the MPOE–PLA films and the lower the glass transition temperature of the copolymers. The synthesized copolymers were used to prepare microspheres by the double-emulsion method. The PLA microspheres possess a smooth surface, whereas those made from copolymers have a rough surface with irregularity increasing with the molecular weight of MPOE. The size of these microspheres depends on the amphiphilic nature of the copolymers, their hydrophilicity, and their intrinsic viscosity in the organic solvent. © 1998 John Wiley & Sons, Inc. J Appl Polym Sci 68: 1695–1702, 1998     

鱼精蛋白对PLA微球佐剂的调控

采用快速膜乳化法,以聚乳酸(PLA)为材料,分别以乙酸乙酯和二氯甲烷为有机溶剂,制备了粒径400和900 nm的均一PLA微球和鱼精蛋白(PS)修饰的PLA-PS微球,以微球为佐剂、HBsAg为抗原免疫小鼠,在动物水平上研究其免疫调控作用,考察了不同粒径微球对抗原体内免疫效果的影响. 结果表明,鱼精蛋白修饰后的PLA微球对乙肝表面抗原的吸附率增加,未修饰的PLA微球对抗原的吸附率仅为2.07%,修饰后吸附率为8.16%;修饰后微球为佐剂的免疫效果优于未修饰微球为佐剂的免疫效果,鱼精蛋白修饰能显著提升小鼠脾细胞分泌Th1型细胞因子(IL-2和IFN-γ)数(分别提升了261%和139%),分泌Th2型细胞因子IL-4数增加了67%;用修饰后平均粒径400 nm微球为佐剂免疫小鼠,IL-2分泌水平是900 nm微球为佐剂的1.68倍.     

Microspheres of copolymeric <Emphasis Type="Italic">N</Emphasis>-vinylpyrrolidone and 2-ethoxyethyl methacrylate for the controlled release of nifedipine

Free radical copolymerization of N-vinyl-2-pyrrolidone (NVP) with 2-ethoxyethyl methacrylate (EOEMA) was carried out with 2,2′-azobisisobutyronitrile (AIBN) initiator in 1,4-dioxane solvent at 60 °C. The resulting copolymers were characterized by FTIR, ¹H-NMR and ¹³C-NMR methods. Microspheres were prepared by varying the amount of NVP with respect to EOEMA. Nifedipine (NFD), a water-insoluble antihypertensive drug, was loaded into these microspheres by the oil in water emulsion technique followed by solvent evaporation. The effect of the proportion of NVP in the NVP/EOEMA copolymer on the controlled release of NFD from the microsphere matrix was investigated. Scanning electron micrographs (SEM) of the microspheres indicated spherical shapes in the size range 17–47 μm, even after loading with NFD. In vitro studies of the release of NFD from the NVP/EOEMA microspheres in pH 7.4 medium showed that the rate of NFD release was enhanced when the NVP content of the copolymer was high; the size of the microspheres also increased with increasing NVP content of the copolymer. Release data were analyzed using an empirical relation in order to elucidate the kinetics of the NFD release. This analysis indicated that a Fickian transport mode operates in this system.     

聚乳酸微球的制备及应用

以聚乳酸(PLA)为基体材料,选择聚乙烯醇(PVAL)为乳化剂.采用乳化-溶剂挥发法制备形态较好的PLA微球.在固定可确定因素、保证成球质量的基础上,分别通过调节乳化剂的浓度和其它因素在一定范围内来控制微球的平均粒径.实验结果表明,PLA浓度、乳化剂浓度、搅拌速度、滴加速度4个因素时微球性能影响显著.通过正交实验摸索出制得粒径约为100 μm的PLA微球的最佳工艺方案:搅拌速度为600 r/min,PLA浓度为0.09g/mL,PVAL浓度为0.005 g/mL,滴加速度为1.5 mL/min.这为下一步将此工艺应用于载药微球的研究奠定了基础.     

聚乳酸微球的制备工艺研究

以聚乳酸为基础材料,选择聚乙烯醇为乳化剂,采用O/W乳化-溶剂挥发法制备形态较好的聚乳酸微球.在可确定因素固定下来后,在保证成球质量的基础上,分别通过调节乳化剂的浓度和其它因素在一定范围内来控制微球的平均粒径.单因素实验结果表明,PLA浓度、乳化剂浓度、搅拌速度、滴加速度对微球性能影响显著.通过正交实验得出制备粒径大小为100 μm左右聚乳酸微球的最佳工艺方案为:搅拌速度600 r·min-1,PLA浓度9%(g·mL-1),PVA浓度0.5%(g·mL-1),滴加速度1.5 mL·min-1.     

聚乳酸共混膜的制备与表征

以聚乳酸(PLA)为膜基材、动物油或植物油为添加剂、二氯甲烷为溶剂,通过流延法制备聚乳酸共混膜。考察添加剂种类、添加剂与PLA的质量比对膜的表面结构与相关性能的影响。结果表明:制备的聚乳酸共混膜具有"海岛"结构;随着添加剂与PLA质量比值的增大,共混膜的"岛径"、接触角、弹性模量、渗析系数和铵根离子的累积渗透量均呈现有规律性的变化,具有良好的可调节性,在包膜缓控释肥料领域具有发展潜力。