Ray Sayantan, Ghosh Ray Suparna, Mandal Supratim
a Department of Quality Assurance , Stadmed Pvt. Ltd. , Kolkata , West Bengal , India.
b Department of Radiotherapy , Calcutta National Medical College , Kolkata , West Bengal , India.
Artif Cells Nanomed Biotechnol. 2017 Aug;45(5):944-954. doi: 10.1080/21691401.2016.1196457. Epub 2016 Jun 21.
In this study we report the development and optimization of poly (D, L-lactide-co-glycolide) (PLGA) polymer encapsulated poorly aqueous soluble nonsteroidal antiandrogen drug bicalutamide, to develop a sustained release formulation for the treatment of prostate cancer. The bicalutamide-loaded PLGA nanoparticles were prepared by single emulsion (O/W) solvent evaporation method, and different process parameters like polymer concentration in the organic phase, surfactant concentration in aqueous phase and centrifugation speed for separation of nanoparticles were evaluated to optimize the drug-loaded nanoparticles. The optimum formulation of bicalutamide-loaded PLGA nanoparticles characterized extensively by different analytical techniques like laser light scattering to determine average particle size and size distribution, scanning electron microscopy (SEM) for surface morphology, powder X-ray diffraction (PXRD) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. Significant decrease of crystallinity of bicalutamide confirms entrapment of the drug within the PLGA polymer matrix. Further, the drug encapsulation efficiency (EE) and in vitro drug release profile were measured by high-performance liquid chromatography and UV-spectrophotometry. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release up to 5 days. Optimum formulation of bicalutamide-loaded PLGA nanoparticles shows significant anti-tumor activity over prostate cancer cell lines (DU 145). The newly developed optimum formulation nanoparticles could be useful for sustained release delivery of bicalutamide.
在本研究中，我们报告了聚（D，L-丙交酯-共-乙交酯）（PLGA）聚合物包裹难溶于水的非甾体抗雄激素药物比卡鲁胺的研发与优化，以开发一种用于治疗前列腺癌的缓释制剂。采用单乳液（O/W）溶剂蒸发法制备了载比卡鲁胺的PLGA纳米粒，并对不同工艺参数进行了评估，如有机相中聚合物浓度、水相中表面活性剂浓度以及分离纳米粒的离心速度，以优化载药纳米粒。通过不同的分析技术对载比卡鲁胺的PLGA纳米粒的最佳配方进行了广泛表征，如用激光散射法测定平均粒径和粒径分布，用扫描电子显微镜（SEM）观察表面形态，用粉末X射线衍射（PXRD）分析表面化学，用差示扫描量热法（DSC）研究热谱性质。比卡鲁胺结晶度的显著降低证实了药物被包裹在PLGA聚合物基质中。此外，通过高效液相色谱法和紫外分光光度法测定了药物包封率（EE）和体外药物释放曲线。体外药物释放呈现双相模式，先是初始突释，随后是缓慢且持续的释放，长达5天。载比卡鲁胺的PLGA纳米粒的最佳配方对前列腺癌细胞系（DU 145）显示出显著的抗肿瘤活性。新开发的最佳配方纳米粒可用于比卡鲁胺的缓释递送。
