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Therapeutic Efficacy and Biodistribution of Paclitaxel-Bound Amphiphilic Cyclodextrin Nanoparticles: Analyses in 3D Tumor Culture and Tumor-Bearing Animals In Vivo

机译:紫杉醇结合的两亲性环糊精纳米粒子的治疗疗效和生物分布:体内3D肿瘤培养和肿瘤瘤动物分析

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摘要

The uniqueness of paclitaxel’s antimitotic action mechanism has fueled research toward its application in more effective and safer cancer treatments. However, the low water solubility, recrystallization, and side effects hinder the clinical success of classic paclitaxel chemotherapy. The aim of this study was to evaluate the in vivo efficacy and biodistribution of paclitaxel encapsulated in injectable amphiphilic cyclodextrin nanoparticles of different surface charges. It was found that paclitaxel-loaded amphiphilic cyclodextrin nanoparticles showed an antitumoral effect earlier than the drug solution. Moreover, the blank nanoparticles reduced the tumor growth with a similar trend to the paclitaxel solution. At 24 h, the nanoparticles had not accumulated in the heart and lungs according to the biodistribution assessed by in vivo imaging. Therefore, our results indicated that the amphiphilic cyclodextrin nanoparticles are potentially devoid of cardiac toxicity, which limits the clinical use and commercialization of certain polymeric nanoparticles. In conclusion, the amphiphilic cyclodextrin nanoparticles with different surface charge increased the efficiency of paclitaxel in vitro and in vivo. Cyclodextrin nanoparticles could be a good candidate vehicle for intravenous paclitaxel delivery.
机译:紫杉醇的抗阳性动作机制的独特性促进了在更有效和更安全的癌症治疗中的应用研究。然而,低水溶性,重结晶和副作用阻碍了经典紫杉醇化疗的临床成功。本研究的目的是评估紫杉醇的体内疗效和生物分布,其包封在不同表面电荷的可注射两亲环糊精纳米粒子中。发现紫杉醇加载的两亲性环糊精纳米颗粒表现出比药物溶液更早的抗肿瘤效果。此外,空白纳米颗粒与紫杉醇溶液的相似趋势降低了肿瘤生长。在24小时,根据通过体内成像评估的生物分布,纳米颗粒在心脏和肺中累积。因此,我们的结果表明两亲性环糊精纳米颗粒可能缺乏心脏毒性,这限制了某些聚合物纳米颗粒的临床用途和商业化。总之,具有不同表面电荷的两亲性环糊精纳米颗粒在体外和体内紫杉醇提高了紫杉醇的效率。环糊精纳米颗粒可以是静脉内紫杉醇递送的良好候选载体。

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