Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, Egypt.
Drug Deliv. 2022 Dec;29(1):1863-1877. doi: 10.1080/10717544.2022.2072544.
Pancreatic cancer (PC) frequency and incidence have grown rapidly in recent years. One of the most serious problems with PC is the existence of asymptotic manifestations, which frequently delays early detection, and until the diagnosis is established, tumor cells progress to the metastatic stage. Another significant concern with PC is the scarcity of well-defined pharmacotherapeutic drugs. The aim of this study was to develop an efficient nanocarrier system to augment the efficacy of raloxifene (RLX) against PC cells. As a result, the current investigation was carried out in order to give an effective treatment method, in which an optimum RLX loaded phospholipid-based vesicles with melittin (PL-MEL) was chosen using experimental design software, with particle size, zeta potential and entrapment efficiency % as dependent variables. Furthermore, anticancer activity against PANC1 cells was assessed. The optimized nanovesicle parameters were 172.5 nm for the measured size, zeta potential of -0.69 mV, and entrapment efficiency of 76.91% that were in good agreement with the expected ones. RLX-raw, plain formula, and optimized RLX-PL-MEL showed IC concentrations of 26.07 ± 0.98, 9.166 ± 0.34, and 1.24 ± 0.05 µg/mL, respectively. Furthermore, cell cycle analysis revealed that the nanovesicle was most effective in the G2-M phase, whereas Bax, and Bcl-2 estimates revealed that optimized RLX formula had the highest apoptotic activity among treatments investigated. However, as compared to RLX alone or plain formula alone, the optimized formula demonstrated higher expression of TNFα and Bax while a significant reduction of Bcl-2 and NF-κB expression was observed. mitochondrial membrane potential (MMP) analysis confirmed the apoptosis as well as the anticancer effect of the optimized formula. Thus, the present study results showed an improvement in the anti-PC effects of the RLX with phospholipid conjugated melittin, making it a novel treatment approach against PC.
近年来，胰腺癌（PC）的发病率和频率迅速增长。PC 最严重的问题之一是存在亚临床表现，这经常延迟早期检测，直到诊断确立，肿瘤细胞才进展到转移阶段。PC 另一个重要问题是缺乏明确的药物治疗药物。本研究的目的是开发一种有效的纳米载体系统，以提高雷洛昔芬（RLX）对 PC 细胞的疗效。因此，进行了这项研究，以提供一种有效的治疗方法，其中使用实验设计软件选择了载有蜂毒素（PL-MEL）的最佳 RLX 载磷脂纳米囊泡，以粒径、Zeta 电位和包封效率%为因变量。此外，还评估了对 PANC1 细胞的抗癌活性。优化的纳米囊泡参数为测量尺寸为 172.5nm，Zeta 电位为-0.69mV，包封效率为 76.91%，与预期值吻合良好。RLX-原药、普通配方和优化的 RLX-PL-MEL 的 IC 浓度分别为 26.07±0.98μg/mL、9.166±0.34μg/mL和 1.24±0.05μg/mL。此外，细胞周期分析表明，纳米囊泡在 G2-M 期最有效，而 Bax 和 Bcl-2 估计表明，在所研究的治疗中，优化的配方具有最高的凋亡活性。然而，与 RLX 单独或普通配方单独相比，优化的配方显示出更高的 TNFα 和 Bax 表达，而 Bcl-2 和 NF-κB 表达显著降低。线粒体膜电位（MMP）分析证实了优化配方的凋亡和抗癌作用。因此，本研究结果表明，磷脂结合蜂毒素的 RLX 的抗 PC 作用得到了改善，为 PC 的治疗提供了一种新方法。
