A docetaxel-carboxymethylcellulose nanoparticle outperforms the approved taxane nanoformulation, Abraxane, in mouse tumor models with significant control of metastases.

Abstract

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.

• Authors: Mark J Ernsting, Mami Murakami, Elijus Undzys, Ahmed Aman, Barry Press, Shyh-Dar Li
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 162 Issue 3 Pg. 575-81 (Sep 28 2012) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 22967490 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Albumin-Bound Paclitaxel
• Albumins
• Antineoplastic Agents
• Delayed-Action Preparations
• Taxoids
• Docetaxel
• Carboxymethylcellulose Sodium
• Paclitaxel

Topics

• Albumin-Bound Paclitaxel
• Albumins (administration & dosage, pharmacokinetics)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Carboxymethylcellulose Sodium (administration & dosage, pharmacokinetics)
• Cell Line, Tumor
• Delayed-Action Preparations (administration & dosage, pharmacokinetics)
• Docetaxel
• Female
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, SCID
• Nanoparticles (administration & dosage)
• Neoplasms (drug therapy, pathology)
• Paclitaxel (administration & dosage, pharmacokinetics)
• Taxoids (administration & dosage, pharmacokinetics)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays