Department of Applied Chemistry, Graduate School of Engineering , Kyushu University , 744 Motooka , Nishi-ku, Fukuoka 819-0395 , Japan.
Advanced Transdermal Drug Delivery System Center , Kyushu University , 744 Motooka , Nishi-ku, Fukuoka 819-0395 , Japan.
Mol Pharm. 2018 Jun 4;15(6):2484-2488. doi: 10.1021/acs.molpharmaceut.8b00305. Epub 2018 May 18.
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.
紫杉醇（PTX）注射液（即 Taxol）已被用作治疗各种癌症的有效化疗药物。然而，目前的 Taxol 制剂中含有 Cremophor EL，这会导致静脉注射时产生过敏反应，并在水稀释时沉淀。本通讯报道了基于离子液体（IL）的 PTX 制剂的初步研究结果，旨在解决上述问题。这些制剂由 PTX/胆碱氨基酸 IL/乙醇/Tween-80/水组成。观察到 PTX 的溶解度显著提高，与 IL 的密度和粘度以及用作 IL 阴离子的氨基酸的侧链有很大的相关性。此外，这些制剂在 3 个月内稳定。该制剂稳定的驱动力被假设为 IL 与 PTX 之间存在不同类型的相互作用。在 HeLa 细胞上评估了基于 IL 的制剂的体外细胞毒性和抗肿瘤活性。不含 PTX 的 IL 载体被发现比 Taxol 的细胞毒性更小，而基于 IL 的 PTX 制剂和 Taxol 均表现出相似的抗肿瘤活性。最后，在 THP-1 细胞上评估了体外过敏反应，发现基于 IL 的制剂比 Taxol 显著降低。这项研究表明，专门设计的 IL 可以作为 Cremophor EL 的一种潜在更安全的替代品，为癌症治疗提供有效的 PTX 制剂，减少过敏反应。
