多西他赛Pluronic F127聚合物胶束的制备与表征

目的制备多西他赛(DTX)的F127聚合物胶束,对其药剂学特征进行评价。方法薄膜分散法制备胶束,并在单因素考察的基础上,以正交试验优化处方;透射电镜观察胶束形态;粒度分布测定仪测定其粒径、粒度分布;离心过滤法测定胶束的包封率和载药量;以DTX注射液作对照,采用动态膜透析法考察载药胶束的体外释药情况。结果薄膜分散法制备的胶束呈球形或类球形,平均粒径为(30.2±2.56)nm,平均包封率为(86.66±2.46)%,平均载药量为(0.42±0.01)%;体外释放实验结果表明该胶束具有一定的缓释能力。结论该胶束制备工艺简单,成型好,包封率高,具有一定的缓释能力。     

玻璃体内注射用地塞米松微球的制备

目的为治疗增殖性玻璃体视网膜病变,制备玻璃体内注射用地塞米松微球。方法以生物可降解乙交酯和丙交酯的无规共聚物(PLGA)为载体材料,采用W/O型乳化-溶剂挥发方法制备地塞米松微微球。研究影响微球制备的工艺条件,考察了微球的粒径大小与分布、载药量和包封率,评价载药微球的体外释放行为。结果微球形态完整,表面光滑,微球的粒径范围为4.70±1.6μm,载药量为(15.5±0.32)%,包封率为(78.8±1.3)%。体外释药13d约90%,属扩散-溶蚀机制。结论制备方法可行,地塞米松PLGA微球具有药物缓释作用。可以作为玻璃体内注射用地塞米松的给药载体。     

PEG-I-dC16酸敏释药胶束的制备及体外释放研究

目的:构建酸敏释药胶束并考查其酸敏释药特性。方法:用亚胺键连接PEG和苯棕榈酸脂肪链,用透析法制备载阿霉素胶束,对其粒径,载药量和包封率进行考察,用紫外分光光度法测定载药胶束在不同pH值条件下的释放。结果:载药胶束粒径为60~70 nm,PEG相对分子质量为2000 Da的胶束载药量和包封率分别为(12.7±1.1)%和(49.8±2.2)%,PEG相对分子质量为5000 Da的胶束载药量和包封率分别为(10.7±0.3)%和(39.9±2.1)%。体外释放研究表明酸敏释药胶束在pH 6.5时的累积释放率比pH 7.4时大,但在pH 5.0条件下其累积释放较pH 7.4时还要小,可能原因是胶束解聚太快致药物与材料形成复合物沉淀所致。结论:以酸敏感亚胺键连接的两亲材料载药胶束具有一定的酸敏释药特性。     

基于缓释递药系统的姜酮混合胶束构建及其评价

目的： 研究混合胶束包载姜酮后的药物性能以及对治疗非酒精性脂肪肝（NAFLD）的影响。方法：采用薄膜分散法制备姜酮/F68/F127/TPGS混合胶束（Z-TPGS-Ms）,通过单因素试验筛选最优处方,观察胶束形态,测定粒径、包封率及载药量,考察胶束稳定性。通过体外释放实验和体内药动学考察Z-TPGS-Ms释放效果,并建立非酒精性脂肪肝细胞模型,考察抗NAFLD作用。结果：Z-TPGS-Ms粒径为（20.78 ± 1.32）nm,包封率和载药量分别为（98.01% ± 0.17%）和（6.47% ± 1.06%）。Z-TPGS-Ms稳定性良好,体外累积释放率明显高于原料药,实现姜酮在体内缓慢释放。与姜酮相比,Z-TPGS-Ms治疗NAFLD效果明显改善。结论：基于缓释递药系统制备的姜酮混合胶束稳定、均一、载药量高,可实现缓释递药,提高体外治疗NAFLD效果。     

PCL-PEG-PCL载姜黄素纳米粒子的制备以及体外药物释放的考察

目的制备一种生物可降解、生物相容性良好的姜黄素纳米粒子,并对其体外药物释放行为进行考察。方法采用开环聚合法制备生物可降解的PCL-PEG-PCL三嵌段聚合物,然后采用乳液挥发法制备负载姜黄素的PCL-PEG-PCL纳米粒子,通过透射电镜观察所制备纳米粒子的形貌特征,动态光散射(DLS)测定粒径,采用HPLC测定纳米粒子的包封率和载药量,同时考察其体外药物释放行为。结果姜黄素纳米粒子具有球形结构,粒径在200 nm左右,载药量为(14.23±0.35)%,3 d体外累积释药量65%。结论所制备的姜黄素纳米粒子具有较高的载药量和包封率,同时体外药物释放实验证实姜黄素纳米粒子具有良好的缓释功能。     

N-琥珀酰壳聚糖纳米粒的制备及体外评价

目的制备N-琥珀酰壳聚糖纳米粒并对其进行体外评价。方法采用乳化溶剂挥发法制备N-琥珀酰壳聚糖纳米粒;以包封率、载药量及粒径为指标,采用正交设计法对处方进行优化;考察其理化特征及体外释药行为。结果纳米粒包封率及载药量分别为62.36%和18.98%,平均粒径及zeta电位分别为(206.6±64.7)nm和(-27.2±0.2)mV;1 h药物释放达到45%,随后药物的释药行为是一个缓释过程。结论作者采用乳化溶剂挥发法成功制得N-琥珀酰壳聚糖纳米粒。该方法制得纳米粒包封率较高,制备工艺简单。     

阿霉素-五味子乙素pH敏感聚合物胶束的制备与制剂学性质

目的以p H敏感聚合物聚乙二醇-聚乳酸-聚组氨酸[poly(ethyleneglyco1)-poly(D,L-lactide)-poly(L-histidine),m PEG-PLA-PHis]胶束为载体,联合包载抗肿瘤药物阿霉素与多药耐药逆转剂五味子乙素制备聚合物胶束,并对其制剂学性质进行研究。方法采用薄膜分散法制备阿霉素-五味子乙素p H敏感聚合物胶束,以包封率、载药量和稳定性(载药胶束24 h的包封率和载药量变化)为评价指标,采用单因素试验及Box-Behnken效应面法筛选最优处方;应用透射电子显微镜观察载药胶束的外观形态,动态光散射法测定载药胶束的粒径及zeta电位;透析法考察载药胶束在不同p H条件下的释药行为。结果制备的阿霉素-五味子乙素p H敏感聚合物胶束平均粒径为64.73 nm,zeta电位为-8.7 m V。最优处方中阿霉素包封率为95.3%,载药量为8.7%,五味子乙素包封率为76.1%,载药量为3.4%,载药胶束稳定性较好。体外释放结果表明,所制备的阿霉素-五味子乙素p H敏感聚合物胶束在弱酸性条件下,药物释放速率明显加快。结论采用星点设计-效应面法优化处方与制备工艺,所制备的阿霉素-五味子乙素p H敏感聚合物胶束粒径分布均匀,包封率和载药量良好,具有明显的p H响应行为。     

槲皮素包合物微球的制备及其体外释放研究

目的:制备槲皮素β-环糊精包合物-壳聚糖微球(QT-CD-CM),并考察其理化性质和药物体外释放性能。方法:采用有机溶剂挥发法制备槲皮素β-环糊精包合物,再用乳化分散-离子交联法、以三聚磷酸钠为交联剂制备壳聚糖微球,并考察其形态、粒径、包封率、载药量和体外释放情况。结果:制备的QT-CD-CM形态规则、均质、无粘连,平均粒径(3.327±0.124)μm,包封率为32.4%,载药量为12.3%,在5%乙醇-磷酸盐缓冲液介质中72h可以达到完全释药,释药过程符合一级动力学模型。结论:QT-CD-CM理化性质及体外释药性能良好,制备工艺简单,有望成为理想的槲皮素给药系统。     

透明质酸修饰的PAMAM纳米胶束的制备及性质研究

目的采用透明质酸(HA)修饰聚酰胺-胺(PAMAM)树状大分子,以姜黄素、阿霉素为模型药物,构建HA-PAMAM纳米胶束肿瘤主动靶向给药系统。方法采用酰胺化反应合成不同透明质酸取代度的HA-PAMAM;采用溶剂挥发法制备HA-PAMAM单药和双药联合载药胶束;采用高效液相色谱法测定姜黄素、阿霉素的包封率和载药量;通过体外透析法研究载药胶束的释药特性。结果采用溶剂挥发法制备阿霉素、姜黄素单药或联合载药胶束,载药胶束的包封率与载药量较高(姜黄素分别为66.70%、6.57%,阿霉素分别为82.14%、33.15%)。HA-PAMAM载药胶束体外释放显示出良好的缓释性能。结论透明质酸修饰的PAMAM是一种具有良好肿瘤靶向性应用前景的纳米载药系统。     

姜黄素聚合物胶束的制备及体外评价

目的:制备姜黄素的Soluplus聚合物胶束,并对其进行体外评价。方法:采用薄膜分散法制备姜黄素聚合物胶束;采用粒径测定仪、透射电镜、X-射线衍射(XRD)对其进行表征;采用紫外分光光度法测定胶束的包封率和载药量;采用动态膜透析法考察载药胶束的体外释药特性。结果:薄膜分散法制备的胶束呈球形或类球形,平均粒径为(65.54±2.57)nm,平均包封率为(87.73±2.94)%,平均载药量(7.96±2.13)%;XRD结果表明姜黄素以无定型状态或分子状态包载在聚合物胶束中;体外释放结果表明姜黄素的soluplus聚合物胶束具有缓释作用。结论:该胶束制备工艺简单,其粒径、包封率、载药量可控,具有缓释作用。     

Preparation of Tacrolimus loaded micelles based on poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone)

Self-assembled polymeric micelles are widely applied in drug delivery system. In this study, Tacrolimus (FK506) loaded micelles were prepared based on biodegradable poly(?-caprolactone)-poly(ethylene glycol)-poly(?-caprolactone) (PCEC) copolymers. Micelles were prepared by self-assembly of triblock copolymer PCEC in distilled water triggered by its amphiphilic characteristics. Drug loading and encapsulation efficiency were determined by adjusting the weight ratio of FK506 and PCEC. The particle size distribution and variation of obtained micelles were determined using Malvern laser particle size analyzer, while the spherical geometry was observed on transmission electron microscope (TEM), and the crystallographic assays were fulfilled by X-ray diffractometer (XRD). Besides, in vitro release profile demonstrated a significant difference between rapid release of free Tacrolimus and much slower and sustained release of FK506 loaded micelles. These results suggested that we have successfully prepared Tacrolimus loaded micelles in an improved method which is safer and more efficient. The prepared micelles might be potential carriers for Tacrolimus delivery in immunosuppressive therapy.     

艾塞那肽聚乳酸-羟基乙酸共聚物纳米粒的制备及其分析方法研究

目的以聚乳酸-羟基乙酸共聚物(PLGA)为载体,用乳化复乳法制备包载艾塞那肽(EX)的PLGA纳米粒(EX-PLGANPs),并对其分析方法进行研究。方法2018年10月至2019年8月,采用Box-Behnken Design(BBD)响应面分析法对纳米粒制备的处方工艺进行优化,动态光散射技术检测EX-PLGA NPs粒径和Zeta电位;通过高效液相色谱法(HPLC)测定EX-PLGANPs中艾塞那肽含量并进行方法学验证。结果制备的EX-PLGA NPs粒径为(157.2±3.1)nm,Zeta电位为(¹19.5±2.6)mV;载药量和包封率分别为(4.41±0.28)%和(73.43±0.59)%,透射电镜图显示纳米粒外观圆整,分布均匀;EX-PLGA NPs体外稳定性良好,透析袋法释放结果显示其具有缓释效果。结论制备的EX-PLGA NPs粒径分布均一,包封率和载药量高,稳定性好,艾塞那肽含量分析方法科学有效,为艾塞那肽抗糖尿病口服缓释制剂的分析和开发提供了实验基础。     

复合碳酸钙空腔纳米粒的制备及性能评价

目的 制备甘草次酸/海藻酸钠修饰碳酸钙空腔纳米粒并进行体外评价。方法 以可溶性淀粉为模板剂制备中空球状碳酸钙纳米粒（CaCO3 Nps）;在非均相体系中合成了甘草次酸/海藻酸钠聚合物（GA-ALG）;并以聚合物（GA-ALG）为壳以中空结构的碳酸钙纳米粒为核,合成了壳核结构的GA-ALG-CaCO3 Nps。采用Malvern粒度分析仪测定纳米粒子的粒度分布和Zeta电位,并通过SEM对纳米粒的形态进行表征。应用荧光分光光度计评价载盐酸阿霉素（DOX）纳米粒的载药量、包封率及体外释放特征。结果 纳米粒分布均一,平均粒径为（425.4±31.1）nm,PDI为0.289,Zeta 电位为（-17.0±0.3）mV。药物的载药量为（13.06±0.51）%,包封率为（78.35±3.08）%。;体外释放结果显示,纳米粒具有一定的缓释作用。结论 GA-ALG-CaCO3 Nps作为新型的药物载体,具有良好的pH响应性,并能显著提高载药量,还具有明显的缓释效果,为新型的纳米给药系统的深入研究提供参考。     

瑞德西韦聚合物纳米胶束的制备及表征

目的 改良瑞德西韦现有剂型,构建瑞德西韦聚合物纳米胶束,并对其体外特性进行表征.方法 采用生物可降解材料甲氧基聚乙二醇-b-聚D,L-丙交酯(mPEG-b-PDLLA),并用固体分散法制备瑞德西韦聚合物胶束.利用透射电子显微镜与马尔文激光粒度测定仪分析胶束的形态与粒径,用X射线单晶体衍射仪定性测试胶束包裹效果,并通过高...     

Effect of chitosan on physicochemical properties of exenatide-loaded PLGA nanoparticles

The aim of this study was to test stability of exenatide and compare physicochemical properties of PLGA nanoparticles. To make small, stable, uniform and highly encapsulated nanoparticles, various factors such as the components (polymer and stabilizer) and preparation condition (organic phase, temperature or sonication time) were considered. We tested the effect of organic phase, acid/base, ultrasonication time or temperature on exenatide to decide preparation condition of PLGA nanoparticles. And, PLGA nanoparticles were prepared by the double emulsion-solvent evaporation method and chitosan was selected as stabilizer. PLGA nanoparticles were characterized by yield, encapsulation efficiency, drug loading, particle size, zeta potential, polydispersity index and morphology. In this study, PLGA nanoparticles showed different physicochemical properties according to chitosan molecular weight. In case of particle size, PLGA nanoparticles using 0.5 g chitosan (4 kDa) showed biggest particle size (781.4 ± 24.1 nm) among PLGA nanoparticles prepared in this study and PLGA nanoparticles using 1 g chitosan (2 kDa) showed highest encapsulation efficiency (52.8 ± 1.7 %) among PLGA nanoparticles prepared in this study. And, all of PLGA nanoparticles using chitosan showed that polydispersity index was low and zeta-potential was increased. These results suggest that chitosan molecular weight affects physicochemical properties of PLGA nanoparticle.     

姜黄素聚合物胶束的制备及抗肿瘤活性评价

目的:制备姜黄素的维生素E聚乙二醇琥珀酸酯(TPGS)聚合物胶束,从而改善姜黄素的水溶性和抗肿瘤活性。方法:以TPGS为载体材料,采用薄膜水化法制备姜黄素胶束;以包封率和粒径为指标,考察水化温度、水化时间、药载比和水化体积的影响;以包封率、粒径、载药量为指标,经四因素三水平正交试验,确定姜黄素/TPGS胶束的最佳制备工艺;考察姜黄素/TPGS胶束的体外释放度;利用MTT法测试姜黄素/TPGS的体外抗肿瘤活性。结果:姜黄素/TPGS胶束的最佳药载比为1∶40,水化温度为60℃,水化时间为30 min,水化体积为6 mL;所得胶束平均粒径为11.02 nm, Zeta电位为-11.31,载药量为2.65%,包封率为96.20%;姜黄素/TPGS 48 h体外累积释放率为78%,具有一定的缓释性;MTT法表明,姜黄素/TPGS具有良好的抗肿瘤活性。结论:该文采用薄膜水化法制备了一种稳定的姜黄素/TPGS胶束,改善了姜黄素的水溶性,明显提高了其抗肿瘤效果。     

Enhanced cellular uptake of chlorine e6 mediated by stearic acid–grafted chitosan oligosaccharide micelles

Chlorines are attractive compounds for photodynamic therapy because of their high absorption in the red wavelength region. The stearic acid–grafted chitosan oligosaccharide (CSO-SA) micelles have been presented as potential candidates for intracellular drug delivery carrier because of their special structure. In this study, CSO-SA micelles were prepared to encapsulate chlorine e6 (Ce6). The physicochemical properties of synthesized CSO-SA micelles were characterized. The critical micelle concentration (CMC) of CSO-SA with 4.96% amino substituted degree (SD %) was about 36.27?±?1.51?μg/mL. The Ce6-loaded CSO-SA micelles were then prepared by a dialysis method, and the properties and drug release profiles of Ce6-loaded CSO-SA micelles (CSO-SA/Ce6) were investigated. The loading of Ce6 in the CSO-SA micelles could reach higher drug encapsulation efficiency (%), which was ~100%. The size of CSO-SA/Ce6 decreased after the loading of Ce6. The zeta potential of CSO-SA/Ce6 and the drug release rate decreased with the loading content of drug. After the Ce6 molecules were encapsulated into the micelles of CSO-SA, the cellular uptake percentage of Ce6 was much more than that of the free drug. And the cellular uptake percentage of CSO-SA/Ce6 micelles was increased with the incubation time in a short period.     

利福喷丁/聚乳酸-羟基乙酸纳米粒的制备及处方工艺优化

目的： 研制负载利福喷丁的聚乳酸-羟基乙酸共聚物[poly（lactic-co-glycolic acid）,PLGA]纳米粒,并对其处方及制备工艺进行优化。方法： 采用快速膜乳化法制备利福喷丁/PLGA纳米粒。通过单因素实验考察了乳化剂浓度、PLGA浓度、油相/水相体积比、初乳制备转速、初乳制备时间、过膜压力、过膜次数对纳米粒制备的影响。在此基础上以粒径、载药率、包封率为评价指标,使用正交实验设计对纳米粒制备的处方工艺进行优化,以TOPSIS法进行多指标综合分析。然后对最优处方工艺进行验证,并对载药纳米粒的体外释药行为进行考察。结果： 经最优处方工艺制备的载药纳米粒,粒径（428±11.4）nm,粒径分布为（0.186±0.036）,包封率为（76.89±2.6）%,载药率为（10.89±1.2）%。用透视电镜观察呈均匀分布的球形。在体外药物释放实验中,药物在72 h内累计释放了78.81%。结论： 采用快速膜乳化可以简单快捷地制备均匀圆整、包封性好、具有良好缓释性能的利福喷丁/PLGA纳米粒,并为新型抗结核精准治疗的开发提供了基础。