期刊
JOURNAL OF CONTROLLED RELEASE
卷 162, 期 3, 页码 575-581出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2012.07.043
关键词
Paclitaxel; Abraxane; Carboxymethylcellulose; Drug delivery; Docetaxel; Nanoparticles
资金
- Ontario Institute for Cancer Research
- Ontario Ministry of Economic Development and Innovation
- MaRS Innovation [MSC-PoP2011-0193]
- Ontario Centres of Excellence
- Canadian Institutes of Health Research [MOP-258715]
- Coalition to Cure Prostate Cancer Young Investigator Award
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(R)) in mouse models. Cellax increased the systemic exposure of taxanes by 37x compared to Abraxane, and improved the delivery specificity: Cellax uptake was selective to the tumor, liver and spleen, with a 203x 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 24 h. 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. (C) 2012 Elsevier B. V. All rights reserved.
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