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Self-Healable Fast Responsive Poly(ω-Pentadecalactone) Thermogelling System for Effective Liver Cancer Therapy

机译:自愈快速响应的聚(ω-十五内酯)热凝胶体系可有效治疗肝癌。

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摘要

A polyurethane based thermogelling system comprising poly(ω-pentadecalactone) (PPDL), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG), termed as PDEP, was synthesized. The incorporation of PPDL lowers critical micelle concentration (CMC) as well as critical gelation concentration (CGC) of the novel copolymers compared to commercial Pluronic® F127. The thermogels showed excellent thermal stability at high temperature up to 80°C, fast response to temperature change in a time frame of less than second, as well as remarkable self-healing properties after being broken at high strain. In vitro drug release studies using docetaxel (DTX) and cell uptake studies using doxorubicin (DOX) show high potential of the hydrogel as drug reservoir for sustainable release profile of payloads, while the in vivo anti-tumor evaluation using mice model of hepatocellular carcinoma further demonstrated the significant inhibition on the growth of tumor. Together with its excellent biocompatibility in different organs, the novel PDPE thermogelling copolymers reported in this work could potentially be utilized as in situ-forming hydrogels for liver cancer therapy.
机译:合成了基于聚氨酯的热胶凝体系,该体系包括聚(ω-十五烯内酯)(PPDL),聚(乙二醇)(PEG)和聚(丙二醇)(PPG),称为PDEP。与商用Pluronic ® F127相比,PPDL的加入降低了新型共聚物的临界胶束浓度(CMC)和临界胶凝浓度(CGC)。热凝胶在高达80°C的高温下表现出出色的热稳定性,在不到一秒的时间内对温度变化具有快速响应,并且在高应变下破裂后具有出色的自愈特性。使用多西紫杉醇(DTX)进行的体外药物释放研究和使用阿霉素(DOX)的细胞摄取研究表明,水凝胶作为有效载荷可持续释放的药物储库具有很高的潜力,而使用肝细胞癌小鼠模型的体内抗肿瘤评估进一步证明了对肿瘤生长的显着抑制作用。加上其在不同器官中优异的生物相容性,这项工作中报道的新型PDPE热胶凝共聚物有可能被用作肝癌治疗的原位形成水凝胶。

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