Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: An in-vitro investigation
Optimized doxycycline-loaded niosomal formulation for treatment of infection-associated prostate cancer: An in-vitro investigation
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DOI：
10.1016/j.jddst.2020.101715
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发表时间：
2020-06-01
影响因子：
5
通讯作者：
Mousavian, Seyede Maryam
中科院分区：
文献类型：
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作者：
Akbarzadeh, Iman;Yaraki, Mohammad Tavakkoli;Mousavian, Seyede Maryam
开发具有抗菌和抗癌作用的药物递送系统在感染相关癌症，特别是前列腺癌的治疗过程中具有重要意义。在这项研究中，司盘60，吐温60，和胆固醇被用来配制作为一个有前途的药物载体系统，无论是抗菌或抗癌制剂的多西环素加载的类囊泡。采用多目标响应面法优化处方工艺，并对其进行表征。开发的囊泡体制剂显示出长达2周的良好储存稳定性。此外，与生理pH（7.4）相比，它们在酸性溶液（pH = 3）中显示出显著的药物释放。研究了所开发的囊泡体制剂在两种不同应用中的体外性能：抗菌和抗癌。使用不同的革兰氏阴性和革兰氏阳性细菌研究了负载多西环素的囊泡的抗菌特性，其中观察到MIC值的显著（50 - 75%）降低。此外，所述囊泡体制剂还具有针对前列腺癌细胞（PC 3）的有希望的化疗效果，但增强了针对正常HEK293细胞的生物相容性。增强的化疗效果与不同基因的调节以及用囊泡制剂处理后PC 3细胞的细胞周期变化相关。这些载体可能作为一种潜在的药物传递系统用于治疗前列腺癌。
Developing drug delivery systems with both antibacterial and anti-cancer effects is of importance in the treatment process of infection-associated cancers, especially prostate cancer. In this study, Span 60, Tween 60, and cholesterol were used to formulate doxycycline-loaded niosomes as a promising drug carrier system as either antibacterial or anticancer formulation. The formulation process was optimized by multi-objective response surface methodology (RSM), and then characterized. The developed niosomal formulation showed great storage stability for up to 2 weeks. In addition, they showed remarkable drug release in acidic solution (pH = 3) compared with physiological pH (7.4). The in-vitro performances of the as-developed niosomal formulations were investigated for two different applications: antibacterial and anticancer. The antibacterial properties of doxycycline-loaded niosome were investigated using different Gram-negative, and Gram-positive bacteria, where considerable (50-75%) decreases in MIC values were observed. Moreover, the niosomal formulation also possessed promising chemotherapy effects against prostate cancer cells (PC3) but enhanced biocompatibility against normal HEK293 cells. The enhanced chemotherapy effect was correlated to the regulation of different genes as well as changes in cell cycle of PC3 cells after treatment with the niosomal formulation. These carriers could be served as a potential drug delivery system for the treatment of prostate cancer.