Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia.
AAPS PharmSciTech. 2021 Oct 19;22(8):252. doi: 10.1208/s12249-021-02111-w.
Therapeutic efficacy of antineoplastic agents possessing a selective target to the nucleus of the cancer cells could be enhanced through novel formulation approaches. Thus, towards improvement of anticancer potential of icariin (ICA) on pancreatic cancer, the drug was entrapped into the polymeric poly lactic-co-glycolic acid (PLGA) with polyethylene glycol (PEG) as diblock copolymer. Optimization of the formulation was done using Statgraphics software to standardize percentages of PEG-PLGA and tween 80 (TW80) to obtain the smallest particle size. The optimized formulation was found to be in nanometer size and low PDI (0.321). Optimized formula enhanced cytotoxicity and apoptotic potential, compared with ICA-raw, against pancreatic cancer cell lines (aspc-1). The entrapment efficiency of the polymeric micelles was 72.34 ± 2.3% with 93.1 ± 6.5% release of ICA within 72 h. There was a twofold increase in apoptosis and sevenfold increase in necrosis of aspc-1 cells when incubated with raw ICA compared to control cells. Further, loss of mitochondrial membrane potential (⁓50-fold) by the ICA-loaded PMs and free drug compared to control cells was found to be due to the generation of ROS. Findings of cell cycle analysis revealed the significant arrest of G2-M phase of aspc-1 cells when incubated with the optimized formulation. Simultaneously, a significantly increased number of cells in pre-G1 revealed maximum apoptotic potential of the drug when delivered via micellar formulation. Finally, upregulation of caspase-3 established the superiority of the PMs approach against pancreatic cancer. In summary, the acquired results highlighted the potentiality of PMs delivery tool for controlling the growth of pancreatic cancer cells for improved efficacy.
通过新型制剂方法，可以提高针对癌细胞核的抗肿瘤药物的治疗效果。因此，为了提高淫羊藿苷（ICA）对胰腺癌的抗癌潜力，将药物包封到具有聚乙二醇（PEG）的聚合性聚乳酸-共-羟基乙酸（PLGA）中作为二嵌段共聚物。使用 Statgraphics 软件优化制剂，以标准化 PEG-PLGA 和聚山梨酯 80（TW80）的百分比，以获得最小的粒径。优化的制剂被发现为纳米级且 PDI 低（0.321）。与 ICA-原样相比，优化配方增强了细胞毒性和促凋亡作用，针对胰腺癌细胞系（aspc-1）。聚合物胶束的包封效率为 72.34 ± 2.3％，在 72 h 内 ICA 的释放率为 93.1 ± 6.5％。与对照细胞相比，用原 ICA 孵育时，aspc-1 细胞的凋亡增加了两倍，坏死增加了七倍。与对照细胞相比，ICA 负载的 PMs 和游离药物导致线粒体膜电位降低（约 50 倍），这归因于 ROS 的产生。细胞周期分析的结果表明，当用优化配方孵育时，aspc-1 细胞的 G2-M 期显著停滞。同时，在预 G1 中细胞数量的显著增加表明药物的最大促凋亡作用，当通过胶束制剂给药时。最后，半胱天冬酶-3 的上调证实了 PMs 方法在控制胰腺癌方面的优越性。总之，所获得的结果强调了 PMs 传递工具在控制胰腺癌细胞生长以提高疗效方面的潜力。
