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。     

快速膜乳化法制备胸腺法新长效缓释微球

采用快速膜乳化技术结合溶剂蒸发法制备以生物可降解聚乳酸-羟基乙酸(PLGA)为载体的胸腺法新载药微球,考察了PLGA分子量、油相中PLGA和乳化剂浓度、外水相pH值和内水相体积等对微球包埋率和粒径的影响. 结果表明,制备粒径均一的PLGA载药微球的优化条件为：PLGA分子量51 kDa,油相中PLGA和乳化剂浓度为100和10 g/L,内水相体积0.5 mL,外水相pH值为3.5. 该条件下所制载药微球粒径均一性好(Span<0.7),药物包埋率高达80%以上,突释率24 h内低于20%,线性持续稳定释药时间长达30 d.     

负载药物替莫唑胺的纳米羟基磷灰石/聚乳酸-羟基乙酸共聚物微球的缓释行为

以聚乳酸-基乙酸共聚物(PLGA)和纳米羟基磷灰石(nHA)作为生物降解材料制备了药物替莫唑胺(Temozolomide,TMZ)的缓释系统.采用湿法化学工艺制备了球状和棒状的nHA粉末.将TMZ药物分子负载在nHA表面(nHA-TMZ),再通过乳化溶剂挥发法将nHA-TMZ包裹在PLGA微球中,同时研究了微球中nHA的形貌和含量对缓释微球物化性能的影响.用扫描电镜、紫外分光光度计分别测定了微球的结构、形貌、药物包封率和缓释行为.相比于不含有nHA的TMZ/PLGA缓释微球,nHA的介入能够显著提高药物的包封率,并且包封率与nHA的加入量有关.此外,药物释放实验表明包裹在微球中的nHA的形貌和溶解速率能够影响微球的缓释行为.     

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.     

聚(乳酸-羟基乙酸)共聚物PLGA缓释微球的制备及其缓释性能研究

首次以头孢吡肟为球心物质,聚乙烯吡咯烷酮（PVP）为分散剂,采用溶剂挥发法制备了聚（乳酸-羟基乙酸）共聚物PLGA载药微球。透射电镜、光学显微镜测试表明微球球型规则,表面平滑,分布均匀,微球粒径在400nm左右,包覆效果良好,微球栽药率为6．50％,药物包封率为35．75％。经红外光谱（FT—IR）分析得知,两种物质互相融为一体。以pH=7．4的PBS缓冲溶液为释放介质,用紫外分光光度计（UV）对微球的体外释药过程进行了实验,微球在前10d有明显的突释,此后缓慢释药,最终药物释药率达65．30％以上。实验结果表明：PLGA是一种理想的控缓释材料。     

PLGA缓释微球的制备及其释药降解性能研究

以巴比妥为球心物质,聚乙烯吡咯烷酮（PVP）为分散剂,采用溶剂挥发法制备了聚（乳酸-羟基乙酸）共聚物PLGA载药微球。透射电镜、光学显微镜测试表明微球球型规则,表面平滑,分布均匀,微球粒径在400nm左右,包覆效果良好,微球载药率1．039％,药物包封率42．34％。红外（FT—IR）分析得知,两种物质互相融为一体。以PH=7．4的PBS缓冲溶液为释放介质,用紫外分光光度计（UV）对微球的体外释药过程进行了实验,微球在前10天有明显的突释,此后缓慢释药,45天后药物释药率在80％以上。实验结果表明：PLGA是一种理想的控缓释材料。     

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。     

柚皮苷-PLGA微球的制备及表征

目的:制备柚皮苷-PLGA缓释微球,并对其性能进行体外评价.为促骨生长类药物的长效制剂的设计与研发奠定基础.方法:以聚乙烯醇(PVA)、聚乳酸-羟基乙酸共聚物(PLGA)为复合载体材料,采用乳化溶剂挥发法制备柚皮苷-PLGA微球,以微球外观形态、包封率为主要评价指标,单因素投料比(1︰5、1︰10、1︰15)、转速(1...     

快速膜乳化法制备载紫杉醇聚乳酸类微球

采用快速膜乳化法、均质乳化法和超声法制备了聚乳酸(PLA)空白微球,比较了3种方法所制微球的均一性.采用均质乳化法和超声法制备的PLA微球平均粒径分别为1.022和0.987μm,多分散系数分别为0.133和0.145,而快速膜乳化法制备的PLA微球平均粒径为0.906μm,多分散系数为0.005.在此基础上,采用快速膜乳化法制备了聚乳酸、聚(乳酸-羟基乙酸)共聚物(PLGA)和聚(乳酸-聚乙二醇)二嵌段共聚物(PELA)载紫杉醇微球,平均粒径分别为0.906,0.987和1.015μm,多分散系数均为0.005,载药率分别为3.89%,4.93%和3.18%,包埋率分别为63.2%,71.6%和51.3%,在磷酸盐缓冲液中释放60d后,PLGA微球的药物释放率为83.87%,PLA微球为50.25%,PELA微球为41.27%.     

星点设计-效应面法优化鸦胆子油乳酸-羟基乙酸共聚物微球的制备工艺研究

采用乳化溶剂挥发法制备鸦胆子油PLGA微球,以微球的包封率为评价指标,应用星点设计-效应面法考察乳酸-羟基乙酸共聚物(PLGA)的质量浓度、聚乙烯醇(PVA)的质量浓度、鸦胆子油的药物质量浓度对制备工艺的影响,对结果进行多元线性回归和二项式拟合,效应面法优选最佳工艺条件,得到优化后的处方工艺为PLGA质量浓度为6.01mg/m L,PVA的质量浓度为26.52 mg/m L,鸦胆子油的药物质量浓度为90.28 mg/m L,油酸的实测平均包封率为93.8%,与预测值相比,偏差为6.1%。     

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.     

Multiparticulation of ciprofloxacin HCl-encapsulated chitosan microspheres using poly(dl-lactide-co-glycolide)

In this study, we prepared poly(dl-lactide-co-glycolide) (PLGA)-coated chitosan oligosaccharide (COS) microspheres. Ciprofloxacin HCl (CIP)-encapsulated COS microspheres were prepared by the pressure homogenization and spray drying technique. The microspheres have spherical shapes and their particle size was in the range of 2–3 μm in diameter. When they were coated with PLGA, PLGA-coated COS microspheres showed rough spherical surfaces, indicating that COS microspheres might be existed on the surface of particles in addition to the inside of particles. The efficiency of loading and size of particle were increased with the increase of the amount of PLGA feeding amount. At the effect of PLGA series, the loading efficiency and particle size were in the order of RG504H > RG503H > RG502H. Drug release rate was decreased with the increase of the amount of PLGA feeding and initial burst was 3–10 days according to the PLGA feeding amount. At the effect of PLGA series, drug release rate was in the order of RG502H > RG503H > RG504H. When acetone was used, drug release rate was slightly increased. PLGA-coated COS microspheres were successfully prepared and characterized.     

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 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     

壳聚糖季铵盐表面修饰对载紫杉醇PLGA微球体外药效学的影响

采用聚(乳酸-羟基乙酸)共聚物(PLGA)纳微球装载紫杉醇,并用壳聚糖季铵盐(HTCC)对PLGA微球表面进行镀层修饰,比较了修饰前后载药微球的形貌、粒径、电位、载药率、释药行为和细胞杀伤效果. 结果表明,修饰后微球表面圆整光滑,平均粒径为882 nm,载药率可达5.15%,包埋率达70.46%,体外释药22 d累积释药率为70.17%,与修饰前没有显著性差异;但修饰后微球表面电荷由修饰前的-14.8 mV翻转为+36.7 mV,肿瘤细胞对PLGA和HTCC-PLGA载药微球的内吞量分别是Taxol?的5.6和9.7倍,且HTCC-PLGA载药微球对细胞杀伤效果显著,是一种有潜力的难溶性药物递送系统.     

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。     

季铵化两亲性壳聚糖衍生物载药性质研究

合成新型季铵化两亲性壳聚糖衍生物(DEAE-CMC)。用乳化交联固化法制备DEAE-CMC/VB12载药微球。用激光粒径仪、扫描电镜对微球的大小和形态进行表征。载药微球的平均粒径为4.53μm。在pH=7.4磷酸盐缓冲溶液中,DEAE-CMC/VB12载药微球体外药物释放达到平衡时间为60 h,药物包封率为33.70%,载药量为12.47%,平衡时药物累积释放率为56.30%。     

Synthesis and characterization of star-shaped poly (lactide-co-glycolide) and its drug-loaded microspheres

The star-shaped poly (lactide-co-glycolide) (PLGA) was synthesized via the ring-opening polymerization of d,l-lactide and glycolide, with pentaerythritol as a multifunctional initiator and stannous 2-ethyl hexanoate as a catalyst. The structures of these polymers were characterized by ¹³C-NMR spectroscopy, while the molecular weight and polydispersity index (PDI) were determined by gel permeation chromatography (GPC). The glass transition temperature (T _g) of copolymer was determined by differential scanning calorimetry (DSC). Bovine serum albumin (BSA) loaded microspheres were fabricated using star-shaped PLGA by a W/O/W double emulsion solvent evaporation method. The results of characterization demonstrated that the particle size of the PLGA microspheres were about 80–150 μm, the maximum loading capacity and encapsulation efficiency of BSA-loaded microspheres were 67.51 μg/(mg microspheres) and 78.39%, respectively, which were better than linear PLGA. The in vitro release profiles of BSA in phosphate buffer saline (PBS) lasted for 37 h. Drug release profiles can be affected by polymer molecular weight and the ratio of polymer to drug. The maximum release percentage was 80%.