Department of Pharmacy, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, P. R. China.
BMC Pharmacol Toxicol. 2023 Mar 1;24(1):13. doi: 10.1186/s40360-023-00653-2.
Albumin-bound paclitaxel (nab-paclitaxel), as a special targeted preparation of paclitaxel, has the advantages of good curative effect and less side effects in anti-tumor therapy. The existence of the plasma-peritoneal barrier and insufficient blood supply make intravenous drugs hard to reach the peritoneum, while hyperthermic intraperitoneal chemotherapy can solve the difficulty. And compared with systemic medications, HIPEC can also give higher concentrations of chemotherapy drugs in the abdominal cavity, while ensuring lower systemic toxicity. However, at present, there is no relevant report on the clinical study of nab-paclitaxel during intraperitoneal hyperthermic chemotherapy, and its stability under special temperature conditions has not been reported either.
In this study, We examined three batches of albumin-bound paclitaxel dissolved in saline at different temperatures (25 °C, 37 °C, 41 °C, 42 °C and 43 °C) for the changes of human serum albumin content, human serum albumin polymer content, related substance content, in-vitro release rate, paclitaxel binding rate and paclitaxel content at different temperatures.
Our results demonstrated that the indicators including human serum albumin content, human serum albumin polymer content, in-vitro release rate, paclitaxel binding rate and paclitaxel content were stable to the several temperatures, except that Taxane (0.1%) and other individual impurities in the determination of related substance content fluctuated comparatively widely with the change of temperature. In addition, only Taxane (0.1%) and 7-Epitaxol (1%) were detected.
Overall, albumin-bound paclitaxel is relatively stable to different temperatures (25 °C, 37 °C, 41 °C, 42 °C and 43 °C). This study will lay a foundation for further studies on the albumin-bound paclitaxel during hyperthermic intraperitoneal chemotherapy.
白蛋白结合紫杉醇（nab-紫杉醇）作为紫杉醇的一种特殊靶向制剂，在抗肿瘤治疗中具有疗效好、副作用少的优点。由于存在血浆腹膜屏障和血供不足，静脉药物难以到达腹膜，而腹腔内热灌注化疗可以解决这一难题。与全身药物相比，HIPEC 还可以在腹腔内给予更高浓度的化疗药物，同时确保较低的全身毒性。然而，目前尚无关于 nab-紫杉醇在腹腔内热灌注化疗中临床研究的相关报道，其在特殊温度条件下的稳定性也尚未报道。
在这项研究中，我们考察了三批nab-紫杉醇在不同温度（25°C、37°C、41°C、42°C 和 43°C）下溶解在生理盐水中的变化，包括人血清白蛋白含量、人血清白蛋白聚合物含量、有关物质含量、体外释放率、紫杉醇结合率和紫杉醇含量。
我们的结果表明，除了有关物质含量测定中 Taxane（0.1%）和其他个别杂质的变化范围较宽外，人血清白蛋白含量、人血清白蛋白聚合物含量、体外释放率、紫杉醇结合率和紫杉醇含量等指标在几种温度下均较稳定。此外，仅检测到 Taxane（0.1%）和 7-Epitaxol（1%）。
总体而言，白蛋白结合紫杉醇对不同温度（25°C、37°C、41°C、42°C 和 43°C）相对稳定。这项研究将为进一步研究nab-紫杉醇在腹腔内热灌注化疗中的应用奠定基础。
