快速膜乳化法制备载生长激素释放肽-6的PLGA微球

采用快速膜乳化法制备了聚(乳酸-羟基乙酸)(PLGA)微球,得到制备PLGA微球的优化条件为：过膜压力5 kPa,水相中PVA浓度19 g/L,油/水相体积比1:10,该条件下所制空白微球的平均粒径约为24 mm,粒径分布系数Span<0.7. 在此基础上制备载生长激素释放肽-6(GHRP-6)微球,油相乳化剂浓度2.5 g/L、外水相中NaCl浓度10 g/L条件下所制载GHRP-6微球包埋率最高可达85%,初乳制备方式对药物包埋率及体外释放行为均有较大影响,超声法制备的初乳所得微球内部结构紧密,药物包埋率较高(85%),但释药缓慢;而均质法制备的初乳所得微球内部结构疏松,药物包埋率较低(76.8%),但在体外释放更完全.     

聚乳酸-羟基乙酸共聚物微球载药性能的研究

利用三相微流控技术制备聚乳酸-羟基乙酸共聚物(PLGA)微球,并探索微球对水溶性药物的载药量和包封率的影响。结果表明,三相微流控技术制备的PLGA微球大小均一,平均粒径约为49μm。随着内水相模型药物浓度的增加,在保持微球形貌和尺寸均一的前提下,载药量能增加到10. 91%,而药物的包封率仍然维持在96%以上。在PLGA油相中加入油溶性药物,不影响PLGA微球对水溶性药物的载药量和包封率,说明PLGA微球具有优异的载药性能。     

膜乳化法与复乳法结合制备粒径均一的PELA载溶菌酶微球

采用快速膜乳化技术与复乳-溶剂去除法制备了尺寸均一的单甲氧基聚乙二醇-聚-DL-乳酸(PELA)载溶菌酶微球,比较了膜材种类和有机溶剂类型对微球中药物包埋率和活性保持的影响. 研究结果表明,该方法能快速制备粒径均一的载药微球,在油相与外水相体积比为1:6的条件下,微球粒径分布系数小于20%,而且该方法对膜材和有机溶剂有很好的普适性. 以PELA为膜材、乙酸乙酯为有机溶剂,采用溶剂扩散法制备的载药微球包埋率高达95.7%,并且能保持高的活性.     

单分散性PLGA磁性微球的制备及其缓释性

为获得单分散性PLGA磁性微球,以纳米四氧化三铁明胶分散液作为内水相(W1),PLGA(聚乳酸羟基乙酸共聚物)的二氯甲烷溶液作为油相(O),PVA(聚乙烯醇)水溶液作为外水相(W2),利用T型微通道并采用复合乳液法制备PLGA磁性微球,考察油相(O)质量浓度、外水相(W2)质量分数、流速比及油相与内水相体积比对微球制备的影响。借助FTIR、SEM、光学显微镜及VSM(振动样品磁强计)对磁性微球组分、形貌、粒径分布和磁学性能进行表征;并以阿司匹林作为药物模型进行缓释性测试。结果表明:油相中PLGA质量浓度为0.050kg/L,外水相(W2)中PVA质量分数为1%及2%,流速比v(W2)∶v(W1/O)=120∶1且体积比V(O)∶V(W1)=2∶1时可均匀成球,其粒径分布系数CV值仅为4.66%,表现出良好的单分散性;此时,比饱和磁化强度可达1.52emu/g,兼具优异顺磁性。制得的载药微球在60 h内表现出阶段性匀速释放,且有较好的磁响应性,有望用于磁响应性药物载体。     

三七皂苷R1-PLGA纳米微球的制备及优化研究

应用高分子有机化合物聚乳酸-羟基乙酸共聚物[Poly(lactide-co-glycolide),PLGA]作为成膜材料包载三七皂苷R1制备纳米微球并寻求最优制备条件。采用复乳-溶剂挥发法制备纳米微球,使用高效液相色谱仪、激光粒度分析仪,测定包封率及粒径。采用正交实验设计,对影响包封率及粒径的因素分别进行五因素四水平正交实验。在PLGA浓度10mg/m L,内水相∶油相体积比为3∶10,外水相与初乳体积比为10∶1,第一次超声乳化时间10s,第二次超声乳化时间90s的条件下制备的微球包封率最为理想。若要获得最小粒径,则优化实验条件为:PLGA浓度20mg/m L,内水相∶油相体积比为2∶5,外水相与初乳体积比为2∶1,第一次超声乳化时间10s,第二次超声乳化时间120s。以PLGA为外壳材料可制备携三七皂苷R1纳米微球,并能获得其包封率及粒径制备的最优化条件。     

快速膜乳化法制备载醋酸曲普瑞林PLGA微球

以生物可降解聚合物聚(乳酸?羟基乙酸)(PLGA)为载体,以160 g/L明胶水溶液为内水相、含500 g/L PLGA的二氯甲烷为油相,采用快速膜乳化和溶剂蒸发法制备了粒径均一的载醋酸曲普瑞林PLGA微球,微球粒径约30 mm,粒径分布系数Span<0.8,醋酸曲普瑞林包埋率达80.12%,药物在磷酸盐缓冲液中释放36 d的释放率为72.60%,体外释放行为良好.     

奥曲肽长效生物可降解微球的制备工艺研究

运用复乳法制备奥曲肽PLGA长效生物可降解微球,并用正交法优化微球制备工艺。利用HPLC、显微镜、激光粒度仪等对微球进行综合质量研究。结果表明,复乳法制备奥曲肽微球的最佳工艺参数为:内水相药物与中油相PLGA的质量比为1∶5,中油相PLGA的浓度为10%,外水相乳化剂为1%的22 000分子量聚乙烯(PVA)水溶液,中油相与外水相的体积比不小于1∶50,复乳化采用机械搅拌法,搅拌速度为1 200 r/min。在该工艺条件下制得的微球,包封率为35.1%,载药量为2.98%,平均粒径为26.3μm,微球外观圆整,形态良好。     

两亲性刺突微球的制备及性能表征

以两亲性聚合物聚乙二醇-聚(乳酸儃乙醇酸)(mPEG儃PLGA)共聚物为材料,采用复乳法结合溶剂挥发法制备mPEG儃PLGA刺突微球,用其吸附蛋白多肽类药物,考察了膜材组分比、聚乳酸/羟基乙酸(LA/GA)摩尔比、内水相与油相体积比(W1/O)、油相与外水相体积比(O/W2)、固化条件等因素对微球的形貌结构及包埋率的影响.结果表明,优化的制备条件为:mPEG/PLGA分子量比1/19,LA/GA摩尔比50/50,W1/O/0.2,O/W2/1/10,固化搅拌速率500 r/min.该条件下所制微球刺突结构特征明显,包埋率高达70%以上,比表面积是普通光滑微球的14倍.     

快速膜乳化法制备粒径均一的PLGA微球和微囊

以聚(乳酸-羟基乙酸)(PLGA)为膜材,采用快速膜乳化结合溶剂萃取法制备了胰高血糖素样肽-1(GLP-1)微囊,研究了PLGA分子量对药物装载率、药物活性和体外释放行为的影响. 制备均一微球的优化条件为过膜压力1000 kPa,过膜次数3次,外水相稳定剂聚乙烯醇浓度19 g/L,油水体积比1:5. 在此条件下,制备了粒径350 nm左右、多分散系数小于0.050的载GLP-1的PLGA微囊,GLP-1包埋率达65%以上,活性保留达85%以上,药物体外释药可达20 d.     

快速膜乳化法制备尺寸均一的载硫酸亚铁明胶微球

采用快速膜乳化技术,以大豆油为油相、葡萄糖为固化剂,制备均一载硫酸亚铁明胶微球,考察了制备参数对明胶微球形貌和均一性的影响. 结果表明,优化的制备参数为明胶溶液浓度0.200 g/mL、乳化剂浓度0.07 g/mL、初乳均质转速10000 r/min、固化反应时间20 min. 在该条件下制备了球形圆整、平均粒径为50 μm的均一载FeSO4明胶微球,FeSO4包埋率达44.12%,Fe2+含量为60.8%.     

快速膜乳化与热固化法制备粒径均一的pH敏感壳聚糖季铵盐凝胶微球

以具有升温自固化特性的壳聚糖季铵盐/甘油磷酸钠混合溶液为水相,利用快速膜乳化与热固化法制备了粒径均一、pH敏感的壳聚糖季铵盐凝胶微球,考察了跨膜压力、水油相组成、水油相体积比及微孔膜孔径等对微球粒径、结构和药物包埋率的影响. 结果表明,得到粒径698±57.33, 1145±71.48, 2021±53.63及3984±191.72 nm、粒径分布窄(多分散系数<0.1)、药物包埋率高达75.49%±2.62%的凝胶微球. 所制微球生物相容性好,有明显的pH敏感性,中性和碱性环境下结构稳定,药物缓释,pH=7.4时24 h内药物累计释放率为34.6%;酸性环境下微球崩解,药物快速释放,pH=5.5时1 h内药物累计释放率高达79.6%.     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

5-FU-PLGA复乳微球的制备及体外释放

采用乳化溶剂挥发法制备W/O/W型5-FU-PLGA复乳微球,采用单因素设计考察了第一相体积比(内水相与油相)、第二相体积比(初乳与外水相)对复乳稳定性的影响,采用正交设计考察了搅拌温度、搅拌时间、辅料浓度和有机相中载体材料浓度对微球质量的影响,并对制备条件进行优化。最适宜制备条件为:第一相体积比为1:2,第二相体积比为1:1,搅拌温度为10 ℃、搅拌时间为6 h、辅料浓度为0.5%、有机相中载体材料浓度为15%。依据最适宜条件制备的微球圆整度良好、粒径范围窄,平均粒径5.20 μm,载药量为5.34%,包封率为77.22%。体外释放试验表明微球具有明显的缓释效果,释放行为符合Higuchi模型。     

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres with a controllable particle size based on a composite emulsion and their release properties for curcumin loading

Because of their unique magnetic features and good biocompatibility, magnetic poly(lactic‐co‐glycolic) acid (PLGA) microspheres have great application potential in magnetic targeted drug‐delivery systems. In this research, magnetic PLGA microspheres with controllable particle sizes were successfully prepared from a composite emulsion with a T‐shaped microchannel reactor. A water‐in‐oil‐in‐water composite emulsion was generated by the injection of a dichloromethane/gelatin water‐in‐oil initial emulsion into the microchannel together with a coating aqueous phase, that is, the aqueous solution of glucose and poly(vinyl alcohol). The mean particle size of the microspheres could be controlled by the manipulation of the osmotic pressure difference between the internal and external aqueous phases via changes in the glucose concentration. Curcumin, a drug with an inhibitory effect on tumor cells, was used to exemplify the release properties of the magnetic PLGA microspheres. We found that the mean particle size of the microspheres ranged from 16 to 207 μm with glucose concentrations from 0 to 20 wt %. The resulting microspheres showed a rapid magnetic response, good superparamagnetism, and a considerable magnetocaloric effect, with a maximum magnetic entropy of 0.061 J·kg^?1·K^?1 at 325 K. An encapsulation efficiency of up to 77.9% was achieved at a loading ratio of 3.2% curcumin. A release ratio of 72.4% curcumin from the magnetic PLGA microspheres was achieved within 120 h in a phosphate‐buffered solution. The magnetic PLGA microspheres showed potential to be used as drug carriers for magnetic targeted tumor therapy. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43317.     

Preparation of microspheres with microballoons inside for floating drug‐delivery systems

The use of floating drug‐delivery systems is one method that is used to achieve prolonged gastric residence times. We developed a novel, multiple‐unit, floating drug‐delivery system of microspheres with microballoons inside from xanthan gum (XG) and gelatin (GA) by a water‐in‐oil method. With theophylline as the model drug, four formulations (FI–FIV) with different ratios of the two polymers were prepared. The size distribution, drug‐encapsulation efficiency, floating behavior, release characteristics, and morphological properties were investigated. The ratio of the two polymers influenced the size distribution, encapsulation efficiency, and drug release appreciably. With increasing amounts of GA, the percentage yield of the floating microspheres and the drug‐encapsulation efficiency decreased from 100 and 84.5% to 31 and 56.2%, respectively. The drug‐release rate also decreased with increasing GA content, which was attributed to an increase in the crosslinking extent. An initial burst was observed, and after that, the drug was released slowly by a near‐zero‐order pattern, which was attributed to the low solubility of theophylline and the possible complexes formed by XG and GA in the simulated gastric fluid (pH 1.2). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 197–202, 2004     

Preparation of magnetic poly(lactic‐co‐glycolic acid) microspheres featuring monodispersity and controllable particle size using a microchannel device

Poly(lactic‐co‐glycolic acid) (PLGA) microspheres prepared using a traditional solvent evaporation or double emulsification method are usually polydisperse with an uncontrollable particle size distribution, which brings about poor application performance. In our research, monodisperse magnetic PLGA microspheres were prepared using a microchannel device based on a water‐in‐oil‐in‐water composite emulsion. The composite emulsion was formed by injecting a dichloromethane–gelatin water‐in‐oil emulsion into a microchannel together with an external water phase, i.e. poly(vinyl alcohol) (PVA) aqueous solution. Mean particle size control of the microspheres was executed using the osmotic pressure difference between internal and external aqueous phases caused by regulating NaCl concentration in PVA aqueous phase. It is found that monodisperse magnetic PLGA microspheres with high magnetic responsiveness can be successfully prepared combining the microchannel device with composite emulsion method. Mean particle size of the microspheres with coefficient of variation value below 4.72% is controllable from 123 to 203 µm depending on the osmotic pressure. The resulting samples have pyknotic and smooth surfaces, as well as spherical appearance. These monodisperse magnetic PLGA microspheres with good superparamagnetism and magnetic mobility have potential use as drug carriers for uniform release and magnetic targeting hyperthermia in biological fields. © 2015 Society of Chemical Industry     

单分散性PLGA磁性微球制备及其缓释性研究

为获得单分散性PLGA磁性微球,文中以纳米四氧化三铁明胶分散液作为内水相(W1),PLGA（聚乳酸羟基乙酸共聚物）的二氯甲烷溶液作为油相(O),PVA（聚乙烯醇）水溶液作为外水相(W2),利用T型微通道并采用复合乳液法制备PLGA磁性微球,考察流速比和油相与内水相体积比对微球制备的影响。借助FTIR、SEM及VSM（振动样品磁强计）对磁性微球组分、形貌、粒径分布和磁学性能进行表征;并以阿司匹林作为药物模型进行缓释性测试。结果表明：流速比v(W2):v(W1/O)=120:1且体积比V(O):V(W1)=2:1时可均匀成球,其粒径分布系数CV值仅为4.66%,表现出良好单分散性;此时比饱和磁化强度可达1.52emu/g,兼具优异顺磁性。制得的载药微球在60h内表现出阶段性匀速释放,且有较好磁响应性,有望用于磁响应性药物载体。