Co-delivery of 5-fluorouracil and oxaliplatin in novel poly (3-hydroxybutyrate-co-3-hydroxyvalerate acid)/poly (lactic-co-glycolic acid) nanoparticles for colon cancer therapy
Co-delivery of 5-fluorouracil and oxaliplatin in novel poly (3-hydroxybutyrate-co-3-hydroxyvalerate acid)/poly (lactic-co-glycolic acid) nanoparticles for colon cancer therapy
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DOI：
10.1016/j.ijbiomac.2018.09.119
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发表时间：
2019-03-01
影响因子：
8.2
通讯作者：
Dorkoosh, Farid Abedin
中科院分区：
文献类型：
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作者：
Handali, Somayeh;Moghimipour, Eskandar;Dorkoosh, Farid Abedin
在本研究中，开发了一种新的5FU和OXA共负载的PHBV/PLGA NPs，可诱导癌细胞凋亡。采用双乳液法制备NPs，并采用响应面法（RSM）进行d -最优设计。5FU-OXA负载的NPs通过SEM， DSC和DLS进行评价。扫描电镜显示NPs呈球形，DSC结果表明两种药物均成功捕获到NPs中。负载5FU-OXA的NPs对癌细胞的细胞毒性作用高于游离药物。据我们所知，这些结果首次表明NPs传递的5FU和OXA诱导了更多的ROS生成和更强的ROS依赖性凋亡途径的激活。此外，观察到NPs具有血液相容性。与游离药物联合相比，共载NPs的抗肿瘤效率显著提高，表明这种共载系统在癌症治疗中具有巨大的潜力。本研究结果也证实了PHBV/PLGA NPs可以作为抗肿瘤药物共递送的一个有前景的平台，为减少药物副作用治疗癌症提供了新的视角。(C) 2018 Elsevier B.V.版权所有
In the present study, a novel 5FU and OXA co-loaded PHBV/PLGA NPs was developed which induced apoptosis in cancer cells. NPs were prepared by the double emulsion method and their preparation was optimized using D-optimal design of response surface methodology (RSM). 5FU-OXA loaded NPs were evaluated by SEM, DSC and DLS. NPs were spherical as shown by SEM and the results of DSC indicated that both drugs successfully entrapped into NPs. 5FU-OXA loaded NPs exhibited higher cytotoxicity effect than free drugs on cancer cells. For the first time to our knowledge, these results showed that more ROS generation and stronger activation of the ROS-dependent apoptotic pathway were induced by 5FU and OXA delivered by NPs. Furthermore, it was observed that NPs were hemocompatible. Co-loaded NPs exhibited significantly higher antitumor efficiency compared to free drugs combination, indicating this co-delivery system provides great potential in cancer therapy. The results of present study also confirmed that PHBV/PLGA NPs can be served as a promising platform for the co-delivery of antitumor drugs and present a new view for treatment of cancer with reducing side effect of drugs. (C) 2018 Elsevier B.V. All rights reserved.