Purdue University, Department of Industrial and Physical Pharmacy, West Lafayette 47907, USA.
Purdue University, Electrical and Computer Engineering Technology, West Lafayette 47907, USA.
J Control Release. 2014 Feb 28;176:76-85. doi: 10.1016/j.jconrel.2013.12.018. Epub 2013 Dec 27.
The aim of the present study was to prepare and evaluate a paclitaxel nanocrystal-based formulation stabilized by serum protein transferrin in a non-covalent manner. The pure paclitaxel nanocrystals were first prepared using an antisolvent precipitation method augmented by sonication. The serum protein transferrin was selected for use after evaluating the stabilizing effect of several serum proteins including albumin and immunoglobulin G. The formulation contained approximately 55-60% drug and was stable for at least 3months at 4°C. In vivo antitumor efficacy studies using mice inoculated with KB cells demonstrate significantly higher tumor inhibition rate of 45.1% for paclitaxel-transferrin formulation compared to 28.8% for paclitaxel nanosuspension treatment alone. Interestingly, the Taxol(®) formulation showed higher antitumor activity than the paclitaxel-transferrin formulation, achieving a 93.3% tumor inhibition rate 12days post initial dosing. However, the paclitaxel-transferrin formulation showed a lower level of toxicity, which is indicated by a steady increase in body weight of mice over the treatment period. In comparison, treatment with Taxol(®) resulted in toxicity issues as body weight decreased. These results suggest the potential benefit of using a serum protein in a non-covalent manner in conjunction with paclitaxel nanocrystals as a promising drug delivery model for anticancer therapy.
本研究旨在制备并评价一种以血清蛋白转铁蛋白非共价方式稳定的紫杉醇纳米晶制剂。首先采用抗溶剂沉淀法结合超声处理制备纯紫杉醇纳米晶。在评价了几种血清蛋白（包括白蛋白和免疫球蛋白 G）的稳定效果后，选择了转铁蛋白用于该制剂。该制剂含有约 55-60%的药物，在 4°C 下至少稳定 3 个月。使用接种 KB 细胞的小鼠进行的体内抗肿瘤功效研究表明，与紫杉醇纳米混悬剂单独治疗（28.8%）相比，紫杉醇-转铁蛋白制剂的肿瘤抑制率显著提高（45.1%）。有趣的是，与紫杉醇-转铁蛋白制剂相比，Taxol（®）制剂表现出更高的抗肿瘤活性，在初始给药后 12 天达到 93.3%的肿瘤抑制率。然而，紫杉醇-转铁蛋白制剂的毒性较低，这表现为在治疗期间小鼠的体重稳步增加。相比之下，Taxol（®）治疗导致毒性问题，体重下降。这些结果表明，以非共价方式使用血清蛋白与紫杉醇纳米晶结合作为一种有前途的抗癌治疗药物递送模型具有潜在益处。
