Jose S, Sowmya S, Cinu T A, Aleykutty N A, Thomas S, Souto E B
University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India.
University College of Pharmacy, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kottayam 686631, Kerala, India.
Eur J Pharm Sci. 2014 Oct 15;63:29-35. doi: 10.1016/j.ejps.2014.06.024. Epub 2014 Jul 8.
The present paper focuses on the development and in vitro/in vivo characterization of nanoparticles composed of poly-(D,L)-Lactide-co-Glycolide (PLGA) loading Bacoside-A, as a new approach for the brain delivery of the neuroprotective drug for the treatment of neurodegenerative disorders (e.g. Alzheimer Disease). Bacoside-A-loaded PLGA nanoparticles were prepared via o/w emulsion solvent evaporation technique. Surface of the nanoparticles were modified by coating with polysorbate 80 to facilitate the crossing of the blood brain barrier (BBB), and the processing parameters (i.e. sonication time, the concentration of polymer (PLGA) and surfactant (polysorbate 80), and drug-polymer ratio) were optimized with the aim to achieve a high production yield. Brain targeting potential of the nanoparticles was evaluated by in vivo studies using Wistar albino rats. The nanoparticles produced by optimal formulation were within the nanosized range (70-200 nm) with relatively low polydispersity index (0.391 ± 1.2). The encapsulation efficiency of Bacoside-A in PLGA nanoparticles was 57.11 ± 7.11%, with a drug loading capacity of 20.5 ± 1.98%. SEM images showed the spherical shape of the PLGA nanoparticles, whereas their low crystallinity was demonstrated by X-ray studies, which also confirmed no chemical interactions between the drug and polymer molecules. The in vitro release of Bacoside-A from the PLGA nanoparticles followed a sustained release pattern with a maximum release of up to 83.04 ± 2.55% in 48 h. When compared to pure drug solution (2.56 ± 1.23 μg/g tissue), in vivo study demonstrated higher brain concentration of Bacoside-A (23.94 ± 1.74 μg/g tissue) suggesting a significant role of surface coated nanoparticles on brain targeting. The results indicate the potential of surface modified PLGA nanoparticles for the delivery of Bacoside-A to the brain.
本文重点研究了负载胡黄连苷A的聚（D，L）-丙交酯-乙交酯共聚物（PLGA）纳米颗粒的研制及其体外/体内特性，这是一种用于神经保护药物脑内递送以治疗神经退行性疾病（如阿尔茨海默病）的新方法。通过水包油乳液溶剂蒸发技术制备了负载胡黄连苷A的PLGA纳米颗粒。用聚山梨酯80包被纳米颗粒表面以促进血脑屏障（BBB）的穿越，并对工艺参数（即超声处理时间、聚合物（PLGA）和表面活性剂（聚山梨酯80）的浓度以及药物-聚合物比例）进行了优化，目的是实现高产率。通过使用Wistar白化大鼠的体内研究评估了纳米颗粒的脑靶向潜力。最佳配方制备的纳米颗粒粒径在纳米范围内（70 - 200 nm），多分散指数相对较低（0.391±1.2）。胡黄连苷A在PLGA纳米颗粒中的包封率为57.11±7.11%，载药量为20.5±1.98%。扫描电子显微镜（SEM）图像显示PLGA纳米颗粒呈球形，而X射线研究表明其结晶度较低，这也证实了药物与聚合物分子之间没有化学相互作用。胡黄连苷A从PLGA纳米颗粒中的体外释放呈持续释放模式，48小时内最大释放量高达83.04±2.55%。与纯药物溶液（2.56±1.23μg/g组织）相比，体内研究表明胡黄连苷A在脑内的浓度更高（23.94±1.74μg/g组织），这表明表面包被的纳米颗粒在脑靶向方面发挥了重要作用。结果表明表面改性的PLGA纳米颗粒具有将胡黄连苷A递送至脑内的潜力。
