Ionic-Liquid-Based Paclitaxel Preparation: A New Potential Formulation for Cancer Treatment
Ionic-Liquid-Based Paclitaxel Preparation: A New Potential Formulation for Cancer Treatment
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DOI：
10.1021/acs.molpharmaceut.8b00305
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发表时间：
2018-06-01
影响因子：
4.9
通讯作者：
Goto, Masahiro
中科院分区：
文献类型：
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作者：
Chowdhury, Md. Raihan;Moshikur, Rahman Md;Goto, Masahiro
紫杉醇（PTX）注射剂（即紫杉醇）已被用作各种癌症的有效化疗药物。然而，目前的紫杉醇制剂含有Cremophor EL，在静脉给药和水稀释沉淀过程中会引起过敏反应。本文报告了为解决上述问题而开发的基于离子液体（IL）的PTX配方的初步结果。该配方由PTX/胆碱氨基酸ILs/乙醇/吐温-80/水组成。观察到PTX的溶解度显著增强，这与il的密度和粘度以及il中用作阴离子的氨基酸侧链有相当大的相关性。而且，制剂的稳定性可达3个月。假设该配方稳定性的驱动力是IL和PTX之间不同类型的相互作用的参与。体外细胞毒性和抗肿瘤活性对HeLa细胞进行了评价。不含PTX的IL载体的细胞毒性低于紫杉醇，而基于IL的PTX制剂和紫杉醇具有相似的抗肿瘤活性。最后，对THP-1细胞进行体外超敏反应评估，发现il基制剂明显低于紫杉醇。这项研究表明，特别设计的il可以提供一种潜在的更安全的替代Cremophor EL作为一种有效的PTX制剂，用于癌症治疗，具有更少的过敏反应。
Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.