白藜芦醇PLGA长效注射微球的制备及工艺考察

目的采用乳化溶剂挥发法制备白藜芦醇聚乳酸羟基乙酸[poly(lactic-co-glycolic acid),PL-GA]长效微球,评价各因素对微球性质的影响。方法以微球的包封率、载药量、突释和粒径作为微球的质量评价指标,研究分散相与连续相的体积比、PLGA浓度、聚乙烯醇(polyvinyl alcohol,PVA)浓度、搅拌速度对微球性质的影响,并优化白藜芦醇PLGA微球的制备工艺。结果分散相与连续相的体积比为1∶50时,包封率高,但4 h突释量达到76%,当分散相与连续相体积比由1∶50提升到1∶150时,突释降低了22%;随着聚合物浓度的增加粒径明显增大,突释显著降低;理论载药量对粒径影响不大,在高载药量时突释显著减少;搅拌速度的增加使粒径减小,突释增加;PVA浓度的增加对粒径没有明显的影响,但当PVA的质量浓度从1 g.L-1增加到5 g.L-1时,包封率从93.57%降低到80.31%。结论分散相与连续相的体积比、PLGA浓度、PVA浓度、搅拌速度对微球性质有很大的影响。优化条件下制备的微球形态完整,载药量为(27.86±1.00)%,包封率为(93.57±2.87)%,平均粒径约为21.12μm。白藜芦醇PLGA微球体外释放25 d的累积释药率达(94.04±4.94)%,有望研制成1个月给药1次的给药系统。     

罗哌卡因-醋酸地塞米松PLGA微球的制备及体外释药特性研究

目的 制备罗哌卡因 醋酸地塞米松聚乳酸羟基乙酸共聚物（PLGA）微球（简称微球）并研究其体外释药特性。方法以PLGA为载体,采用W1/O/W2双重乳化 溶剂挥发法制备微球,研究实验过程中有机相PLGA浓度、外水相/有机相体积比、内水相体积、外水相聚乙烯醇（PVA）浓度几项因素变化对罗哌卡因 醋酸地塞米松PLGA微球粒径、表面形态﹑载药量﹑包封率和突释行为的影响。结果有机相PLGA浓度在制备微球的过程中是一个关键性因素。随着PLGA浓度增加,微球粒径增大,载药量﹑包封率明显提高,突释降低;外水相/有机相体积比增大,微球粒径增大, 载药量﹑包封率明显提高,微球表面更加光滑﹑微孔减少,突释降低;随着内水相体积增加使得微球表面的微孔明显增多,突释增加,载药量﹑包封率降低;当外水相PVA浓度由0.5%增加到2%,微球粒径变小,突释效应增加。通过优化条件制备的微球形状为球形,外观光滑圆整,粒径分布均匀,其中＞90%分布在20～70 μm。罗哌卡因载药量（7.48±0.33）%,包封率（70.97±2.36）%;醋酸地塞米松载药量（1.52±0.16）%,包封率（57.30±1.17）%。结论采用W1/O/W2双重乳化 溶剂挥发法成功制备罗哌卡因加醋酸地塞米松PLGA微球;以优化工艺制备的微球,在体外具有明显的缓释行为,释药曲线呈典型S形三阶段模式。     

阿立哌唑缓释微球的制备及体外释放特性的研究

目的 制备阿立哌唑聚乳酸-羟基乙酸共聚物(PLGA)缓释微球并考察其体外释放特性.方法 采用乳化-溶剂挥发法制备阿立哌唑缓释微球,通过正交试验优选最佳处方与制备工艺,并考察其载药量、包封率、粒径、形态和体外释放度.结果 所得微球的载药量为20.28％ ±0.38％,包封率为81.12％±0.02％,平均粒径为19.38 μm,形态圆整,30 d的体外累积释放度达88.73％.结论 所得阿立哌唑缓释微球形态圆整,载药量与包封率较高,具较好的缓释效果.     

一种聚乳酸聚乙醇酸缓释微球的制备工艺

目的:研究一种制备聚乳酸聚乙醇酸(PLGA)微球的新工艺,即将海藻酸钠与钙离子螯合形成缓释凝胶的原理与复乳法制备微球的工艺相结合。方法:以牛血清白蛋白(BSA)为模型药,以包封率、载药量、产率作为评价指标,研究PLGA黏度、海藻酸钠浓度及外水相1中氯化钙浓度对微球性质的影响,并通过L9(34)正交试验设计优选微球制备的工艺条件。结果:优选的制备工艺重现性好,微球形态圆整,结构致密,平均粒径为67.5μm,载药量、包封率和产率分别为0.669%、53.38%和80.08%。结论:本研究获得了较为满意的制备PLGA微球的新工艺,微球的理化性质良好。     

长春西汀聚乳酸-聚乙醇酸缓释微球的研制

目的:制备长春西汀聚乳酸-聚乙醇酸(PLGA)缓释微球,并研究其药剂学性质。方法:采用改良O/W乳化-溶剂挥发法制备微球,以PLGA浓度、理论载药量、有机相与分散介质的比例和分散介质中明胶的浓度为4因素,每个因素选定3个水平,按L9(34)的正交设计方案,以载药量、包封率和粒径分布为指标,优化处方。用扫描电镜观察微球的形态,用光学显微镜观察并计算微球的粒径分布,用差示扫描量热(DSC)法研究药物在载体中的分散状态,用紫外分光光度法检测微球中长春西汀含量并计算载药量和包封率,用动态透析释药法进行微球的体外释放研究。结果:最佳处方为PLGA浓度16%,理论载药量20%,有机相与分散介质的比例1:10,分散介质中明胶的浓度1%;制备的长春西汀PLGA缓释微球的形态圆整、光滑,粒径分布均匀,平均粒径为(10.0±0.18)μm(n=500),DSC法分析药物确已被包裹于微球中,载药量为(18.46±0.26)%,包封率为(91.30±0.98)%(n=3),24h累积释药率约为18%。结论:长春西汀PLGA缓释微球制备工艺稳定,质量符合药剂学要求,缓释性好。     

环糊精衍生物对胸腺喷丁微球突释效应的影响

先将疏水性三乙酰基-β-环糊精(TA-β-CD)和亲水性羟丙基-β-环糊精(HP-β-CD)分别与胸腺喷丁(1)制得共冻干复合物,再采用s/o/w乳化-溶剂挥发法以乳酸-羟基乙酸共聚物(PLGA)为载体制成缓释微球,比较环糊精衍生物对1-PLGA微球载药量、包封率和突释效应的影响,并初步探讨其降低突释效应的机制.结果表明,1-PLGA微球和1-TA-β-CD-PLGA微球的粒径、载药量、包封率和突释率(即24h累积释放率)分别为(62.6±1.2)和(33.9±1.1)μm、(6.37±0.22)％和(8.59±0.19)％、(57.4±0 8)％和(80.4±0.6)％、32.7％和15.2％.而1-HP-β-CD-PLGA微球与1-PLGA微球相比,载药量和包封率反而有所降低,且突释效应未见明显改善.冷场发射扫描电镜、差示扫描量热法和X-射线粉末衍射分析结果表明,在1-TA-β-CD共冻干过程中存在晶型转变,提示药物和辅料间可能发生了相互作用,阻止了1的扩散.     

聚乳酸-羟基乙酸共聚物载药微球性质及缓释行为的影响因素

聚乳酸-羟基乙酸共聚物（PLGA）包裹药物制成缓释微球是药物缓释方向的研究热点,PLGA微球作为载体,具有良好的生物相容性和降解性,但载药微球的性质和释药性能易受很多因素影响,如PLGA相对分子质量,LA/GA比例,微球制备工艺等,这些因素对载药体系在生物医学领域的应用造成一定限制。结合国内外相关文献,本文综述了PLGA微球在制备及释药过程中,影响其理化性质和重要性能的因素,包括载药量,包封率,突释问题等方面,为PLGA微球进一步研究和优化提供思路。     

丹皮酚聚乳酸羟基乙酸微球的制备及体外释药考察

目的:制备丹皮酚聚乳酸羟基乙酸(PLGA)微球,考察其体外释药过程。方法:以丹皮酚为芯材,以PLGA为载体,采用乳化溶剂挥发法制备丹皮酚PLGA微球;以聚乙烯醇质量分数、PLGA质量浓度、药物与PLGA质量比及水油相体积比为考察因素,以包封率和载药量的综合评分为评价指标,采用正交试验优选制备工艺;扫描电镜和光学显微镜观察微球的外观和粒径,并测定其体外释药过程。结果:优选的工艺为聚乙烯醇质量分数0.9%、PLGA质量浓度60g/L、药物与PLGA质量比1∶3、水油相体积比1∶10。制得的微球球型规则,表面平滑,平均粒径为(31.75±0.13)μm。微球的载药量为(21.16±0.51)%,包封率为(66.91±1.62)%,8h体外累积释药量为37%。结论:所选工艺可用于制备丹皮酚PLGA微球,可为缓释药物传递系统的开发提供参考。     

盐酸四环素缓释微球的制备

目的制备盐酸四环素聚乳酸-聚羟基乙酸共聚物(PLGA)微球并优化其工艺。方法采用复乳-溶剂蒸发法制备盐酸四环素PLGA微球,以微球包封率为检测指标,通过单因素试验和正交试验优选最佳制备工艺。结果在优化条件下制备的微球形态规则,粒径为16.72±0.33μm,载药量为0.52%±0.01%,包封率为78.56%±1.05%,微球的体外释药规律符合Higuichi方程(r=0.9986)。结论该制备工艺合理,为制备盐酸四环素PLGA微球提供了理论基础。     

利培酮长效注射微球的制备及体外释放的研究

目的：制备利培酮长效注射微球并考察其体外释放行为。方法：使用乳酸-羟基乙酸共聚物（PLGA）为材料,采用乳化-溶剂挥发法制备利培酮微球,观察微球的形态及粒径,测定微球的载药量和包封率,考察微球的体外释放情况。结果：利培酮微球表面圆整,粒径集中在40～80μm之间。微球的包封率较高,达到80％以上,以低分子量PLGA（50：50）制备的微球,体外突释很高达到40％以上;以高分子量PLGA（75：25）制备的微球,在高载药量时突释较小,可持续释放达3周以上。结论：以高分子量PLGA制备的高载药量的利培酮微球,体外突释较小可缓释达3周以上。     

牛血清白蛋白阳离子微球的制备及体外评价

目的制备牛血清白蛋白（BSA）口服阳离子微球,考察天然阳离子物质壳聚糖（CHS）的加入对蛋白微球的粒径、电动电势、包封率、载药量及体外释放情况的影响。方法以乳酸／羟基乙酸共聚物（PLGA）和壳聚糖（CHS）为载体材料,采用W／O／W复乳-溶剂挥发法制备牛血清白蛋白乳酸／羟基乙酸共聚物-壳聚糖（PLGA／CHS）阳离子微球。通过正交设计优化制备工艺,确定最佳处方。建立准确而简便的蛋白含量测定方法,并对微球进行体外评价。结果最佳处方为：BSA浓度为150g·L^-1、PLGA浓度为8％、外水相体积为80mL、壳聚糖浓度为0．2％。制得的微球形态圆整,平均粒径为（6．9±5．5）μm,为表面荷正电的阳离子微球[ζ电势=00．0±0．6）mV],包封率为（75．4±4．6）％,载药量为（9．3±0．2）％。体外释放结果表明,在模拟胃液和模拟肠液中,壳聚糖的加入均能减少突释,延缓药物的释放。结论与PLGA微球相比,制得的PLGA／CHS阳离子微球表面带正电,具有较高的包封率和载药量,可以延缓药物释放,同时减少突释现象。     

β-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.     

蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球研究进展

缓释微粒给药系统是蛋白质/多肽药物传输系统的一个重要研究方向，聚乳酸和乳酸-羟基乙酸共聚物是制备缓释微球最常用的载体材料。蛋白质/多肽药物聚乳酸/乳酸-羟基乙酸共聚物微球常用的制备方法包括溶剂萃取/挥发法(复乳法)、相分离法和喷雾干燥法。本文总结了微球制备中面临的难点如蛋白质/多肽药物稳定性、包封率、药物突释和药物吸附等问题，并综述了保持药物结构稳定性和生物活性、提高包封率、改善药物释放曲线等微球制备方法和进展。     

In vitro degradation and dissolution behaviours of microspheres prepared by three low molecular weight polyesters

Three low-molecular weight polyesters, poly(L-lactic acid) (PLA), copoly(lactic acid/glycolic acid) (PLGA) and poly(delta-valerolactone) (PV), were used to prepare water-soluble sodium diclofenac-loaded microspheres by using the oil-in-oil (o/o) emulsification-solvent evaporation method. Their micromeritic and physicochemical properties, and degradation and dissolution behaviours were determined in vitro. The results indicate that high encapsulation efficiency and better monodispersity might be achieved by the o/o emulsification-solvent evaporation method, depending on the amount of drug loading used. The slower evaporation of organic solvent from the system during microencapsulation seemed to modify the crystallinity of drug and polyester in the microspheres, determined by powder x-ray diffractometry and differential scanning calorimetry. The in vitro degradation rate of all the microspheres in pH7.4 phosphate buffer solution showed first-order kinetics and ranked in the order of PLGA > PLA > PV microspheres. Furthermore, the first-order release rate was also found in all the microspheres after an initial drug burst and ranked in the order of PLGA> PLA > PV microspheres, too. The relationship between degradation and dissolution behaviours of these microspheres is discussed.     

PLGA and PHBV Microsphere Formulations and Solid-State Characterization: Possible Implications for Local Delivery of Fusidic Acid for the Treatment and Prevention of Orthopaedic Infections

Purpose  To develop and characterize the solid-state properties of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) microspheres for the localized and controlled release of fusidic acid (FA). Methods  The effects of FA loading and polymer composition on the mean diameter, encapsulation efficiency and FA released from the microspheres were determined. The solid-state and phase separation properties of the microspheres were characterized using DSC, XRPD, Raman spectroscopy, SEM, laser confocal and real time recording of single microspheres formation. Results  Above a loading of 1% (w/w) FA phase separated from PLGA polymer and formed distinct spherical FA-rich amorphous microdomains throughout the PLGA microsphere. For FA-loaded PLGA microspheres, encapsulation efficiency and cumulative release increased with initial drug loading. Similarly, cumulative release from FA-loaded PHBV microspheres was increased by FA loading. After the initial burst release, FA was released from PLGA microspheres much slower compared to PHBV microspheres. Conclusions  A unique phase separation phenomenon of FA in PLGA but not in PHBV polymers was observed, driven by coalescence of liquid microdroplets of a DCM-FA-rich phase in the forming microsphere. Electronic supplementary material   The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Sophoridine-loaded PLGA microspheres for lung targeting: preparation,in vitro,and in vivo evaluation

Lung-targeting sophoridine-loaded poly(lactide-co-glycolide) (PLGA) microspheres were constructed by a simple oil-in-oil emulsion-solvent evaporation method. The obtained microspheres were systematically studied on their morphology, size distribution, drug loading, encapsulation efficiency, in vitro release profile, and biodistribution in rats. The drug-loaded microparticles showed as tiny spheres under SEM and had an average size of 17?μm with 90% of the microspheres ranging from 12 to 24?μm. The drug loading and encapsulation efficiency were 65% and 6.5%, respectively. The in vitro drug release behavior of microspheres exhibited an initial burst of 16.6% at 4?h and a sustained-release period of 14 days. Drug concentration in lung tissue of rats was 220.10?μg/g for microspheres and 6.77?μg/g for solution after intraveneous injection for 30?min, respectively. And the microsphere formulation showed a significantly higher drug level in lung tissue than in other major organs and blood samples for 12 days. These results demonstrated that the obtained PLGA microspheres could potentially improve the treatment efficacy of sophoridine against lung cancer.     

盐酸多西环素微球的制备及质量控制

目的:制备盐酸多西环素(DXY)微球并建立其质量控制方法。方法:以乳酸-羟基乙酸共聚物(PLGA)为载体材料,采用O/O型乳化溶剂挥发法制备微球,用光学显微镜观察微球的外观形态和粒径,采用紫外分光光度法测定微球的载药量和体外释放度等。结果:所制微球外观光滑圆整,平均粒径为(49±6.9)μm,跨距为0.9,平均载药量为(3.3±0.2)%,平均包封率为(52.4±3.2)%(n=3),0.5h的累积释放度为28%,并可持续释药30d以上。结论:DXY微球的制备工艺可行,质量可控。     

海藻酸-壳聚糖-聚乳酸羟乙醇酸复合微球的制备及其对蛋白释放的调节

目的制备蛋白的海藻酸-壳聚糖-聚乳酸羟乙醇酸(PLGA)复合微球，以增加蛋白药物的包封率、减少突释和不完全释放。方法以牛血清白蛋白为模型药物采用修饰的乳化、醇洗法制备小粒径海藻酸微囊，再以壳聚糖孵育制得海藻酸-壳聚糖双层微囊，并进一步用PLGA包裹制得复合微球。采用微量BCA试剂盒测定蛋白浓度，考察其包封率及释放行为，改变各种制备因素调节微球的释放特性。结果复合微球粒径约30 μm，形态圆整。与单纯PLGA微球相比，包封率由60%-70%上升至80%以上。复合微球在磷酸盐缓冲液的1 h突释量由40%-50%下降至25%以下，在生理盐水中则进一步下降至5%以下。结论海藻酸-壳聚糖-PLGA复合微球提高了蛋白药物的包封率，减少了药物的突释，并可通过调节PLGA比例调节药物的释放。     

Bupivacaine-loaded biodegradable poly(lactic-co-glycolic) acid microspheres I. Optimization of the drug incorporation into the polymer matrix and modelling of drug release

Bupivacaine has been encapsulated by solvent evaporation method based on O/W emulsion, using poly(DL-lactic-co-glycolic) acid (PLGA) 50:50. The particle size can be controlled by changing stirring rate and polymer concentration. The encapsulation efficiency was affected by polymer concentration and burst effect of bupivacaine released from particles was affected by drug/polymer mass ratio. Orthogonal design was used to optimize the formulation according to drug content, encapsulation efficiency and burst effect. The dissolution profile and release model were evaluated with two different bupivacaine microspheres (bupi-MS) groups including low drug loading (6.41%) and high drug loading (28.92%). It was observed that drug release was affected by drug loading especially the amount of drug crystal attached on surface of bupi-MS. The drug release profile of low drug loaded bupi-MS agreed with Higuchi equation and that of high drug loaded bupi-MS agreed with first order equation.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15?000 microspheres possessed a smooth and round appearance with average particle size of 50?µm or so. The encapsulation percentages of microspheres prepared from PLGA 15?000, 20?000 and 30?000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30?000 microspheres to 3.97% of PLGA 15?000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30°C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.