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Int J Nanomedicine. 2012;7:1587-97. doi: 10.2147/IJN.S29306. Epub 2012 Mar 27.

Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer.

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1
Department of Biochemistry and Molecular Medicine, UC Davis Cancer Center, University of California Davis, Sacramento, CA 95817, USA.

Abstract

BACKGROUND:

A multifunctional telodendrimer-based micelle system was characterized for delivery of imaging and chemotherapy agents to mouse tumor xenografts. Previous optical imaging studies demonstrated qualitatively that these classes of nanoparticles, called nanomicelles, preferentially accumulate at tumor sites in mice. The research reported herein describes the detailed quantitative imaging and biodistribution profiling of nanomicelles loaded with a cargo of paclitaxel.

METHODS:

The telodendrimer was covalently labeled with ¹²⁵I and the nanomicelles were loaded with ¹⁴C-paclitaxel, which allowed measurement of pharmacokinetics and biodistribution in the mice using microSPECT/CT imaging and liquid scintillation counting, respectively.

RESULTS:

The radio imaging data showed preferential accumulation of nanomicelles at the tumor site along with a slower clearance rate than paclitaxel formulated in Cremophor EL (Taxol®). Liquid scintillation counting confirmed that ¹⁴C-labeled paclitaxel sequestered in nanomicelles had increased uptake by tumor tissue and slower pharmacokinetics than Taxol.

CONCLUSION:

Overall, the results indicate that nanomicelle-formulated paclitaxel is a potentially superior formulation compared with Taxol in terms of water solubility, pharmacokinetics, and tumor accumulation, and may be clinically useful for both tumor imaging and improved chemotherapy applications.

KEYWORDS:

imaging guided drug delivery; microSPECT/CT; nanomicelle; paclitaxel; telodendrimer

PMID:
22605931
PMCID:
PMC3352867
DOI:
10.2147/IJN.S29306
[Indexed for MEDLINE]
Free PMC Article
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