Tongji University School of Medicine, Shanghai, China.
Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University school of medicine, Shanghai, China.
Biomed Chromatogr. 2021 Aug;35(8):e5107. doi: 10.1002/bmc.5107. Epub 2021 Apr 15.
Paclitaxel (PTX) is one of the most widely used chemotherapeutic agents. The commercial PTX formulation was based on Cremophor EL and ethanol owing to its poor aqueous solubility. However, Cremophor EL has been shown to cause toxic effects such as life-threatening anaphylaxis. In our study, we diluted PTX in a commercially available 20% (w/v) lipid emulsion (Lip-PTX) in order to avoid Cremophor EL. The purpose of this study was to evaluate the pharmacokinetics and tissue distributions between Lip-PTX and PTX injection. We also investigated the effects of Lip-PTX and PTX injection on human gastric cancer cells HGC-27 by MTT assay. The apoptosis was detected by flow cytometry with Annexin V/propidium iodide (PI) double staining. Furthermore, the safety such as acute toxicity was also assessed. The results showed that PTX in Sprague-Dawley rats administered Lip-PTX exhibited extended half-life, increased clearance (P < 0.05) and smaller area under the concentration-time curve compared with PTX injection and there was little significant difference in the distribution of PTX in Sprague-Dawley rats or tumor-bearing mice between Lip-PTX and PTX injection. The cells treated with Lip-PTX had a higher percentage of apoptosis and a higher G /M phase ratio, which indicated that the anticancer effect of Lip-PTX was significantly better than that of PTX injection. Moreover, our study highlighted the safety of Lip-PTX. This study demonstrated the feasibility and potential advantages of Lip-PTX for clinical therapy.
紫杉醇（PTX）是最广泛使用的化疗药物之一。由于其水溶性差，商业上的 PTX 制剂基于聚氧乙基代蓖麻油（Cremophor EL）和乙醇。然而，Cremophor EL 已被证明会引起毒性作用，如危及生命的过敏反应。在我们的研究中，我们将 PTX 稀释在一种市售的 20%（w/v）脂质乳剂（Lip-PTX）中，以避免使用 Cremophor EL。本研究的目的是评估 Lip-PTX 和 PTX 注射液之间的药代动力学和组织分布。我们还通过 MTT 法研究了 Lip-PTX 和 PTX 注射液对人胃癌细胞 HGC-27 的影响。通过 Annexin V/碘化丙啶（PI）双重染色的流式细胞术检测细胞凋亡。此外，还评估了急性毒性等安全性。结果表明，给予 Lip-PTX 的 Sprague-Dawley 大鼠中的 PTX 表现出延长的半衰期、增加的清除率（P<0.05）和较小的浓度-时间曲线下面积，与 PTX 注射液相比，Sprague-Dawley 大鼠或荷瘤小鼠中 PTX 的分布几乎没有显著差异。用 Lip-PTX 处理的细胞凋亡率更高，G/M 期比例更高，这表明 Lip-PTX 的抗癌作用明显优于 PTX 注射液。此外，我们的研究强调了 Lip-PTX 的安全性。本研究证明了 Lip-PTX 用于临床治疗的可行性和潜在优势。
