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

Wenwu Xiao, Juntao Luo, Teesta Jain, John W. Riggs, Harry P. Tseng, Paul Henderson, Simon R Cherry, Douglas Rowland, Kit Lam

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1587-1597
Number of pages11
JournalInternational Journal of Nanomedicine
Volume7
DOIs
StatePublished - 2012

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Pharmacokinetics
Paclitaxel
Heterografts
Ovarian Neoplasms
Tumors
Imaging techniques
Chemotherapy
Scintillation
Scintillation Counting
Neoplasms
Liquids
Drug Therapy
Micelles
Optical Imaging
Solubility
Radio
Nanoparticles
Tissue
Water
Research

Keywords

  • Imaging guided drug delivery
  • MicroSPECT/CT
  • Nanomicelle
  • Paclitaxel
  • Telodendrimer

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer. / Xiao, Wenwu; Luo, Juntao; Jain, Teesta; Riggs, John W.; Tseng, Harry P.; Henderson, Paul; Cherry, Simon R; Rowland, Douglas; Lam, Kit.

In: International Journal of Nanomedicine, Vol. 7, 2012, p. 1587-1597.

Research output: Contribution to journalArticle

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