Drug Delivery and Formulation, Medicinal Chemistry Platform, Ontario Institute for Cancer Research, 101 College Street, Suite 800, Toronto, Ontario M5G 0A3, Canada.
J Control Release. 2012 Sep 28;162(3):575-81. doi: 10.1016/j.jconrel.2012.07.043. Epub 2012 Aug 10.
Cellax is a PEGylated carboxymethylcellulose conjugate of docetaxel (DTX) which condenses into a 120-nm nanoparticle, and was compared against the approved clinical taxane nanoformulation (Abraxane®) in mouse models. Cellax increased the systemic exposure of taxanes by 37× compared to Abraxane, and improved the delivery specificity: Cellax uptake was selective to the tumor, liver and spleen, with a 203× increase in tumor accumulation compared to Abraxane. The concentration of released DTX in Cellax treated tumors was well above the IC50 for at least 10 d, while paclitaxel released from Abraxane was undetectable after 24h. In s.c. PC3 (prostate) and B16F10 (melanoma) models, Cellax exhibited enhanced efficacy and was better tolerated compared to Abraxane. In an orthotopic 4T1 breast tumor model, Cellax reduced the incidence of lung metastasis to 40% with no metastasic incidence in other tissues. Mice treated with Abraxane displayed increased lung metastasic incidence (>85%) with metastases detected in the bone, liver, spleen and kidney. These results confirm that Cellax is a more effective drug delivery strategy compared to the approved taxane nanomedicine.
Cellax 是一种聚乙二醇化羧甲基纤维素与多西紫杉醇（DTX）的缀合物，可缩合为 120nm 的纳米颗粒，并在小鼠模型中与已批准的临床紫杉醇纳米制剂（Abraxane®）进行了比较。与 Abraxane 相比，Cellax 使紫杉醇的全身暴露增加了 37 倍，并提高了递送的特异性：Cellax 摄取对肿瘤、肝脏和脾脏具有选择性，与 Abraxane 相比，肿瘤的蓄积增加了 203 倍。在 Cellax 治疗的肿瘤中释放的 DTX 浓度至少在 10d 内高于 IC50，而 Abraxane 释放的紫杉醇在 24h 后无法检测到。在皮下 PC3（前列腺）和 B16F10（黑色素瘤）模型中，与 Abraxane 相比，Cellax 表现出增强的疗效且耐受性更好。在原位 4T1 乳腺癌模型中，Cellax 将肺转移的发生率降低到 40%，而其他组织没有转移发生率。用 Abraxane 治疗的小鼠肺转移发生率增加（>85%），在骨骼、肝脏、脾脏和肾脏中检测到转移。这些结果证实，与已批准的紫杉醇纳米药物相比，Cellax 是一种更有效的药物递送策略。
