首页> 外文期刊>International Journal of Pharmaceutics >Antimetastasis and antitumor efficacy promoted by sequential release of vascular disrupting and chemotherapeutic agents from electrospun fibers
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Antimetastasis and antitumor efficacy promoted by sequential release of vascular disrupting and chemotherapeutic agents from electrospun fibers

机译:从电纺纤维中依次释放血管破坏和化学治疗剂可增强抗转移和抗肿瘤功效

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摘要

The vasculature in tumor microenvironment plays important roles in the tumor growth and metastasis, and the combination of vascular disrupting agents with chemotherapeutic drugs should be effective in inhibiting tumor progression. But the dosing schedules are essential to achieve a balance between vascular collapse and intratumoral uptake of chemotherapeutic agents. In the current study, emulsion and blend electrospinning were used to create compartmental fibers accommodating both combretastatin A-4 (CA4) and hydroxycamptothecin (HCPT). The release durations of CA4 and HCPT were modulated through the structure of fibers for dual drug loadings and the inoculation of 2-hydroxypropyl-beta-cyclodextrin in fiber matrices. Under a noncontact cell coculture in Transwell, the sequential release of CA4 and HCPT indicated a sequential killing of endothelial and tumor cells. In an orthotopic breast tumor model, all the CA4/HCPT-loaded fibers showed superior antitumor efficacy and higher survival rate than fibers with loaded individual drug. Compared with fibrous mats with infiltrated free CA4 and fibers with extended release of CA4 for over 30 days, fibers with sustained release of CA4 for 3-7 days from CA4/HCPT-loaded fibers resulted in the most significant antitumor efficacy, tumor vasculature destruction, and the least tumor metastasis to lungs. A judicious selection of CA4 release durations in the combination therapy should be essential to enhance the tumor suppression efficacy and antimetastasis activity.
机译:肿瘤微环境中的脉管系统在肿瘤的生长和转移中起着重要的作用,血管破坏剂与化学治疗药物的结合应有效抑制肿瘤的进展。但是给药方案对于在血管萎缩和肿瘤内化学治疗药物的吸收之间取得平衡至关重要。在当前的研究中,使用乳液静电纺丝和共混物静电纺丝来制造可容纳comretretatin A-4(CA4)和羟基喜树碱(HCPT)的隔室纤维。 CA4和HCPT的释放持续时间是通过用于双重药物负载的纤维结构以及在纤维基质中接种2-羟丙基-β-环糊精来调节的。在Transwell的非接触式细胞共培养中,CA4和HCPT的顺序释放表明内皮细胞和肿瘤细胞被顺序杀死。在原位乳腺肿瘤模型中,所有负载CA4 / HCPT的纤维均比负载单个药物的纤维显示出更高的抗肿瘤功效和更高的存活率。与具有渗透性游离CA4的纤维垫和具有CA30延长释放功能的纤维相比,具有CA4 / HCPT负载的纤维能够持续释放CA4的纤维持续3-7天的纤维具有最显着的抗肿瘤功效,肿瘤血管破坏,并且肿瘤转移到肺的最少。联合治疗中明智选择CA4释放持续时间对于增强肿瘤抑制功效和抗转移活性至关重要。

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