Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, India.
Industrial Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani, India.
Int J Pharm. 2018 Apr 25;541(1-2):198-205. doi: 10.1016/j.ijpharm.2018.02.010. Epub 2018 Feb 21.
The purpose of present investigation was to nano-encapsulate atypical antipsychotic such as Olanzapine in polymeric nanoparticles in order to explore the possibility of minimizing drug associated extrapyramidal adverse effects. The polymeric nanoparticulate systems were prepared using FDA approved polymer, polycaprolactone, by simple technique of nanoprecipitation using factorial design by DoE approach. The significant factors selected for the optimization during formulation development process were polymer content and surfactant concentration at three different levels (3 factorial design). The effect of selected significant factors were studied in depth on significant responses such as particle size and encapsulation efficiency. The optimized formulation was further surface modified with surfactant (polysorbate 80) so as to enhance the brain targeting efficiency of developed nanoparticles via endocytosis pathway. Furthermore, catalepsy was induced in rodent model and the designed formulations were investigated in comparison with pure drug solution for efficiency in decreasing extrapyramidal adverse effects. The results of in vitro characterization studies demonstrated a narrow size distributed nanoparticles (73.28 ± 2.14 nm) with high stability indicating zetapotential (-32.46 ± 1.15 mV) and high encapsulation efficiency (78.77 ± 2.83%). In vitro release studies resulted in an extended release of atypical antipsychotic for 60 h from drug-loaded optimized nanoparticulate formulations. The catalepsy studies in rodent model demonstrated a significant decrease in extra pyramidal adverse effects as compared to the pure atypical antipsychotic. Thus, the designed antipsychotic loaded polymeric nanoparticulate system may be highly promising for the tremendous improvement of antipsychotic therapy with reduced adverse effects.
本研究的目的是将非典型抗精神病药（如奥氮平）纳米包封在聚合物纳米粒中，以探索最小化药物相关锥体外系不良反应的可能性。使用 FDA 批准的聚合物聚己内酯（polycaprolactone），通过采用 DoE 方法的简单纳米沉淀技术制备聚合物纳米粒系统。在制剂开发过程中，选择了显著的因素（聚合物含量和表面活性剂浓度）进行优化，在三个不同水平（3 因子设计）下进行。在选定的显著因素对显著响应（如粒径和包封效率）的影响进行了深入研究。优化的制剂进一步用表面活性剂（聚山梨醇酯 80）进行表面修饰，以通过内吞作用途径提高开发的纳米粒的脑靶向效率。此外，在啮齿动物模型中诱导了僵住症，并将设计的制剂与纯药物溶液进行了比较，以研究其在减少锥体外系不良反应方面的效果。体外特性研究结果表明，纳米粒具有窄的粒径分布（73.28 ± 2.14nm），具有高稳定性，表明 Zeta 电位（-32.46 ± 1.15mV）和高包封效率（78.77 ± 2.83%）。体外释放研究表明，载药优化纳米粒制剂可延长 60 小时释放非典型抗精神病药物。在啮齿动物模型中进行的僵住症研究表明，与纯非典型抗精神病药物相比，该制剂可显著降低锥体外系不良反应。因此，设计的载有抗精神病药物的聚合物纳米粒系统可能为改善抗精神病治疗效果、减少不良反应提供巨大的潜力。
