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。     

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%。     

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。     

聚乳酸-羟基乙酸聚合物载入羟基喜树碱载药纳米粒子的制备及表征

以抗癌药物羟基喜树碱作为模型药物,可降解材料聚乳酸-羟基乙酸(PLGA)为药物负载体,采用溶剂-抗溶剂沉淀法制备聚乳酸-羟基乙酸/羟基喜树碱的载药纳米微球,考察不同溶剂-反溶剂体系对载药包封效果的影响。结果表明,以丙酮-水为溶剂体系制备的载药微球性能较好,形貌外观呈圆球形,球表面圆润光滑,粒度均一,分散效果良好,平均粒径为160 nm,载药微球包封率随着载药量的增加而减小,实测载药量为7.83%的PLGA载药微球,其载药包封率为87.68%,在28 d后溶出累计量约50%,可见以聚乳酸-羟基乙酸为载体制备的羟基喜树碱剂型,缓释作用良好。     

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。     

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。     

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.     

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...     

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。     

非诺贝特聚合物缓释微球的制备及体外实验研究

目的制备可生物降解的具有降血脂作用的非诺贝特聚合物载药微球。方法通过复乳溶剂-挥发法制备非诺贝特缓释微球,表征其形态、粒径,并计算其载药量、包封率:用磷酸盐7.4的磷酸盐缓冲液在37℃溶解微球,并在不同的时间段在286 nm处测得其峰面积,绘制保准曲线,计算累计释放量。通过红外和差示热量扫描法显示其药物化学结构未发生改变。结果微球表面形貌光滑、完整,粒径分布均匀,平均粒径在1μm呈正态分布较好,其包封率在(89.46±0.54)%,载药量为(18.39±0.48)%,随着微球的降解,其缓释作用可以持续12天。结论通过复乳-溶剂挥发法制备的载非诺贝特PLGA缓释微球形态规整,分散性良好,并且能在12天内实现缓控释放。     

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.     

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.     

5-氟尿嘧啶明胶微球的制备、表征及释药性能

为了获得粒径为50～100μm的5-氟尿嘧啶／明胶微球（5-Fu／GMs），采用乳化一化学交联法，讨论了5-Fu用量、乳化剂浓度和水／油比等因素对微球平均粒径、载药量及包封率等的影响。结果表明，5-Fu／明胶质量比为0．5，乳化剂浓度为0．5％和水／油相体积比为1／10时，可获得最大的载药量30．1％和包封率90．2％。体外释药性能表明5-氟尿嘧啶明胶微球具有明显的药物缓释作用。     

Biodegradable Nanoparticles-Loaded PLGA Microcapsule for the Enhanced Encapsulation Efficiency and Controlled Release of Hydrophilic Drug

Recently, nano- and micro-particulate systems have been widely utilized to deliver pharmaceutical compounds to achieve enhanced therapeutic effects and reduced side effects. Poly (DL-lactide-co-glycolide) (PLGA), as one of the biodegradable polyesters, has been widely used to fabricate particulate systems because of advantages including controlled and sustained release, biodegradability, and biocompatibility. However, PLGA is known for low encapsulation efficiency (%) and insufficient controlled release of water-soluble drugs. It would result in fluctuation in the plasma levels and unexpected side effects of drugs. Therefore, the purpose of this work was to develop microcapsules loaded with alginate-coated chitosan that can increase the encapsulation efficiency of the hydrophilic drug while exhibiting a controlled and sustained release profile with reduced initial burst release. The encapsulation of nanoparticles in PLGA microcapsules was done by the emulsion solvent evaporation method. The encapsulation of nanoparticles in PLGA microcapsules was confirmed by scanning electron microscopy and confocal microscopy. The release profile of hydrophilic drugs can further be altered by the chitosan coating. The chitosan coating onto alginate exhibited a less initial burst release and sustained release of the hydrophilic drug. In addition, the encapsulation of alginate nanoparticles and alginate nanoparticles coated with chitosan in PLGA microcapsules was shown to enhance the encapsulation efficiency of a hydrophilic drug. Based on the results, this delivery system could be a promising platform for the high encapsulation efficiency and sustained release with reduced initial burst release of the hydrophilic drug.     

Incorporation of HSA Microparticles Within the Taxol-Loaded In Situ Forming PLGA Microspheres: Synthesis,Characterization, and Drug Release

Taxol-loaded poly(lactic acid-co-glycolic acid) (PLGA) microspheres containing different portions of human serum albumin microparticles (mHSA) were prepared via an in situ forming method. mHSA was obtained using a freezing-induced phase separation method and further surface modified via PLGA chains (g-mHSA). Surface modification of mHSA improved their dispersion within microspheres. Incorporation of 3% mHSA within microspheres increased their size and surface porosity, while g-mHSA decreased their size. Addition of 1.5% and 3% mHSA into microspheres decreased their initial burst release from 40.7% to 21.1% and 10.2%, respectively. Microspheres consisting 1.5% and 3% g-mHSA displayed 29.9% and 33.1% initial burst release, respectively.     

膜乳化技术-复乳法制备载药微囊的研究

以乙交酯和丙交酯的无规共聚物(PLGA)做为包埋材料,采用膜乳化技术结合复乳溶剂挥发法制备BSA载药微囊。研究了膜乳化压力、搅拌速度和固化时间对包封率的影响,以及载药微囊的体外释放行为。分析表明,随着膜乳化压力的增加,包封率会不同程度的降低;当搅拌速度大于200 rpm时,搅拌速度的增加也会导致包封率的降低;固化时间为5h时,包封率最高。采用膜乳化技术,可以有效的缓解载药微囊的突释现象,1个月内的累计释放量可以达到80%以上。     

Exendin-4结构的稳定性及其微球制备

目的分析影响Exendin-4二级结构稳定性的各种因素,并制备Exendin-4微球。方法利用远紫外圆二色光谱(Circular dichroism,CD)技术,分析pH值、温度、高速搅拌、油水界面对Exendin-4二级结构的影响及冰浴和蛋白质保护剂对其二级结构的保护作用。在此基础上,选用乳酸-羟基乙酸共聚物(PLGA)为成球材料,采用复乳法(W/O/W)制备Exendin-4微球,并对其理化性质进行评价。结果优化了实现Exendin-4二级结构稳定性的药剂学方法。制备的Exendin-4微球流动性良好,球形圆整,平均粒径为(25.3±3.2)μm,结构保持完好,微球的载药量约为1.0%,包封率为72.3%±2.4%,微球的释药曲线符合Higuchi释放模型,未发生明显的突释,具有良好的缓释效果。结论采取适当的药剂学方法,可以保证Exendin-4结构的稳定性并制备出理化性质合格的微球。     

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.     

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.