Effect of microfluidization parameters on the physical properties of PEG-PLGA nanoparticles prepared using high pressure microfluidization

The objective of this work was to develop uniformly distributed poly(ethylene glycol) grafted poly(lactide-co-glycolide) (PEG-PLGA) nanoparticles of mean size range ～100–200 nm using ethyl acetate as the solvent. In the multiple emulsion solvent evaporation method a high pressure microfluidization process was adopted to produce the W/O/W multiple emulsion. Non-toxic ethyl acetate was used to solubilize PEG-PLGA. The mean size of nanoparticles obtained was less than 180 nm. The particle size and size distribution were dependent on the microfluidization conditions applied. Mean particle size steadily increased from 121 nm at three passes to 172 nm at 20 passes of the microfluidizer, indicating that over-processing may be detrimental to PEG-PLGA nanoparticles prepared using this technique. There was no significant alteration of the PEG-PLGA matrix, as evidenced from the differential scanning calorimetric studies.     

Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide

Safe and effective oral delivery of peptide is a challenge. Here, we used exenatide and zinc ions (Zn²⁺) to form a complex to explore a meaningful oral-targeted drug-delivery system. Polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA) was used to prepare nanoparticles (NPs) to escape the degradation caused by gastrointestinal enzymes. Transferrin (Tf) was used as a targeting group. PEG-PLGA-NPs and Tf-modified exenatide-Zn²⁺-loaded NPs (Tf-PEG-PLGA-NPs) were uniformly sized spheres according to transmission electron microscopy. The results of pharmacodynamic and pharmacokinetic investigations in vivo were consistent with in vitro studies using Caco-2 cells. Tf enhanced NPs transport in cell-uptake and transmembrane-transport experiments. Our results showed that the relative bioavailability of Tf-exenatide-Zn²⁺-NPs was higher than that of exenatide-Zn²⁺-NPs. The relative bioavailability of Tf-exenatide-Zn²⁺-NPs versus subcutaneous injection of exenatide was 6.45%. This was a preliminary exploration of the oral administration of exenatide, that data from which can be used for future investigations.     

尼莫地平PEG-PLGA纳米粒的制备及其处方优化

目的：负载尼莫地平的聚乙二醇修饰的聚乳酸-羟基乙酸共聚物[poly （ethylene glycol-poly （lactin-co-glycolic acid）,PEG-PLGA）]纳米粒,并对其进行制备工艺、质量评价以及体外释放等相关性研究。方法：以PEG-PLGA为药物载体,采用乳化溶剂挥发法成功制备尼莫地平载药纳米粒。单因素实验和响应面法设计优化处方工艺,透射电子显微镜观察纳米粒形态,激光粒度仪测定其粒径和Zeta电位,HPLC法测定其包封率及载药量并考察其体外释药特性。结果：制备的尼莫地平纳米粒外观呈实心球体,大小均匀且分散性良好;平均粒径为（183.2±3.30） nm,PDI为（0.115±0.049）,Zata电位为（-11.78±2.16） mV;平均包封率为84.99%,平均载药量为2.45%;尼莫地平原料药在4 h时基本释放完全（达到95%左右）,而尼莫地平纳米粒在4 h时释放仅为43.9%,在第24 h时累计释放度达到（83.66±2.57）%。与对照组相比,制剂组释放缓慢,符合实验设计缓释的要求。结论：本实验成功制备了尼莫地平PEG-PLGA纳米粒,其体外释药具有明显缓释特征,为心脑血管疾病的治疗奠定了基础。     

黄芩苷PEG-PLGA纳米胶束的制备、表征及在急性心肌缺血模型大鼠体内的组织分布

目的制备黄芩苷-聚乙二醇-聚乳酸羟基乙酸共聚物(PEG-PLGA)载药纳米胶束,并研究其体外释药性能及在急性心肌缺血模型大鼠体内的组织分布。方法采用正交试验优选黄芩苷PEG-PLGA纳米胶束的制备工艺,优化的黄芩苷PEG-PLGA纳米胶束再进行粒径、Zeta电位和透射电子显微镜(TEM)检测表征,采用体外释放实验、组织分布实验对该载药系统进行评价。结果黄芩苷PEG-PLGA纳米胶束优选的制备工艺条件为黄芩苷-PEG-PLGA的质量比为1∶10,旋转蒸发仪转动速率为80 r/min,水化温度为40℃,优化的黄芩苷PEG-PLGA纳米胶束粒径为(18.5±0.5)nm,Zeta电位为(-10.9±0.7)mV,载药量为(7.9±0.3)%,包封率为(86.2±2.5)%。采用芘测定法检测PEG-PLGA纳米胶束的临界胶束质量浓度为3.8μg/mL,TEM检测发现黄芩苷PEG-PLGA纳米胶束呈现粒径均一的圆球型;体外释放实验表明,黄芩苷PEG-PLGA纳米胶束具有明显的缓释特征;组织分布实验表明黄芩苷PEG-PLGA纳米胶束在正常大鼠脏器中分布大小顺序为肝脾心肾肺脑,而在急性心肌缺血模型大鼠脏器分布大小顺序为肝心脾肾肺脑,与正常大鼠比较,急性心肌缺血模型大鼠心脏中药物浓度在各时间段都呈现明显升高的趋势,在120 min时最高药物质量浓度可达(2 897±135)ng/mL,显著高于正常大鼠中心脏的最高药物浓度(2 411±89)ng/mL,该结果表明,黄芩苷PEG-PLGA纳米胶束在急性心肌缺血区域具有良好的靶向性。结论黄芩苷PEG-PLGA纳米胶束具有良好的载药性能,体外释药缓慢,且可以将药物蓄积于缺血心肌部位,具有良好的心脏靶向性。     

透明质酸修饰的葛根素PEG-PLGA纳米粒的处方工艺优化及其体外评价

目的?以乳酸-羟基乙酸共聚物（PEG-PLGA）为载体,优化纳米沉淀法制备透明质酸修饰的葛根素PEG-PLGA纳米粒（HA/Pue-NPs）,并对其体外性质进行初步评价。方法?以PEG-PLGA为载体材料,透明质酸为表面修饰剂,采用纳米沉淀法制备了透明质酸修饰的HA/Pue-NPs;应用正交实验设计优化处方,对其体外性质进行表征;并采用体外释药行为评价透明质酸修饰HA/Pue-NPs。结果?制备出的载药纳米粒外观呈球形,平均粒径、Zeta电位分别为（88.9±2.2）nm、（-21.9±0.54）mV,载药量及包封率分别为6.75%、78.52%。体外释药试验表明,载药纳米粒释药缓慢,24h的累计释放率为65.8%。结论?透明质酸修饰的葛根素PEG-PLGA纳米粒粒径大小均一,体外性质良好且具有一定的缓释特性。      

载雄激素受体三螺旋形成寡核苷酸PEG-PLGA 纳米粒子的制备与应用

  【目的】 以生物可降解材料聚乙二醇-聚乳酸聚乙醇酸共聚物(PEG-PLGA)制备载雄激素受体三螺旋形成寡核苷酸的纳米粒子(TFO-NPs),并初步探讨其对前列腺癌LNCaP细胞的生长抑制作用? 【方法】 采用改良自乳化溶剂挥发法(modified-SESD)制备TFO-NPs,对其形态?包封率?载药量及体外释放特点进行鉴定?倒置荧光显微镜观察LNCaP细胞对TFO-NPs的摄取情况,四唑盐(MTT)法测定体外细胞毒作用? 【结果】 制备的TFO-NPs呈球形?大小均匀,平均粒径128 nm,平均包封率和载药量分别为72.28%和1.02%,在体外具有缓释作用?LNCaP细胞对TFO-NPs的摄取率显著高于裸TFO?TFO-NPs对LNCaP细胞的抑制作用明显强于裸TFO(P < 0.05),抑制率分别为61.2% ± 6.5%和20.7% ± 3.1%? 【结论】 本法制备的TFO-NPs理化性质优良,在体外能够有效抑制LNCaP细胞的增殖?     

Oral nano-delivery of anticancer ginsenoside 25-OCH3-PPD,a natural inhibitor of the MDM2 oncogene: Nanoparticle preparation,characterization, in vitro and in vivo anti-prostate cancer activity,and mechanisms of action

The Mouse Double Minute 2 (MDM2) oncogene plays a critical role in cancer development and progression through p53-dependent and p53-independent mechanisms. Both natural and synthetic MDM2 inhibitors have been shown anticancer activity against several human cancers. We have recently identified a novel ginsenoside, 25-OCH₃-PPD (GS25), one of the most active anticancer ginsenosides discovered thus far, and have demonstrated its MDM2 inhibition and anticancer activity in various human cancer models, including prostate cancer. However, the oral bioavailability of GS25 is limited, which hampers its further development as an oral anticancer agent. The present study was designed to develop a novel nanoparticle formulation for oral delivery of GS25. After GS25 was successfully encapsulated into PEG-PLGA nanoparticles (GS25NP) and its physicochemical properties were characterized, the efficiency of MDM2 targeting, anticancer efficacy, pharmacokinetics, and safety were evaluated in in vitro and in vivo models of human prostate cancer. Our results indicated that, compared with the unencapsulated GS25, GS25NP demonstrated better MDM2 inhibition, improved oral bioavailability and enhanced in vitro and in vivo activities. In conclusion, the validated nano-formulation for GS25 oral delivery improves its molecular targeting, oral bioavailability and anticancer efficacy, providing a basis for further development of GS25 as a novel agent for cancer therapy and prevention.     

PEG-PLGA包裹的介孔碳纳米给药系统的制备和表征

目的:利用一种简便易行的方法改善介孔碳(MCN)的分散性,并以其为载体构建纳米给药系统,探索其生物应用的效果。方法:利用TEM观察聚乙二醇-聚乳酸-羟基乙酸共聚物(PEG-PLGA)包裹前后MCN的大小和形态变化。稳定性检测用于评估PEG-PLGA包裹的MCN纳米粒(MCNP)的分散性。热效应实验评价MCNP的近红外(NIR)光热转化能力。构建PEG-PLGA包裹的载阿霉素(DOX)的介孔碳给药系统(MCNPD),从Zeta电荷、载药量、释放以及细胞摄取实验对其进行表征。结果:溶液静置24h后,原始MCN几乎完全聚集沉降,而MCNP仍均匀分散;NIR照射后,MCNP表现出很好的热效应;构建的给药系统MCNPD具有较高的载药量,并且呈p H-依赖释放和NIR-触发释放,同时能够很好地摄取进入细胞。结论:PEG-PLGA包裹以提高MCN分散性的方法简单可行,成功构建了一种具有良好分散性的MCN递药载体,利于生物应用。     

醋酸地塞米松PEG-PLGA纳米粒的制备及表征

目的 研究醋酸地塞米松PEG-PLGA纳米粒的制备工艺及影响因素,并优化冻干粉针工艺.方法 采用乳化/溶剂蒸发法制备醋酸地塞米松PEG-PLGA纳米粒,并考察其粒径分布、包封率、载药量等;采用单因素试验筛选出合适的冻干保护剂.结果 醋酸地塞米松PEG-PLGA纳米粒的粒径为91.43±1.00 nm,Zeta电位为-22.73 ±0.57 mv,包封率为88.78％ ±2.10％,载药量为4.95％-±0.23％;10％蔗糖作为冻干保护剂的效果最好,冻于复溶后粒径约117.27 nm.结论 所用制备工艺简单易行,可用于制备醋酸地塞米松PEG-PLGA纳米粒.     

基于PEG-PLGA和CMCS载体制备白藜芦醇纳米粒在结肠癌治疗中的应用＊

目的 为了提高白藜芦醇（Resveratrol，RES）的生物利用度,将其制备成纳米粒子，并研究其体外抗结肠癌的作用。方法 分别以聚乙丙交酯聚乙二醇共聚物（PEG-PLGA）和羧甲基壳聚糖（Carboxymethyl chitosan，CMCS）作为药物载体，采用纳米沉淀法和乳化交联法分别制备了PEG-PLGA共载白藜芦醇纳米粒（RES-PEG-PLGA NPs）和CMCS共载白藜芦醇纳米粒（RES-CMCS NPs），利用紫外分光光度计、激光粒度分析仪和透射电子显微镜等仪器对纳米粒的理化性质进行表征；采用CCK-8检测法测定纳米粒对人结肠癌细胞（SW480）的抗增殖活性，并通过荧光显微镜考察了纳米粒在SW480细胞中的摄取。结果 RES-PEG-PLGA NPs粒径为78.67 ± 1.0 nm，包封率为87%；RES-CMCS NPs粒径为231 ± 1.6 nm,包封率为60%。结论 两种纳米粒在模拟肿瘤微环境下均能实现白藜芦醇的缓释，都可以有效地被SW480细胞摄取，并且对SW480细胞表现出较高的抑制作用。