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

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:

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

Acknowledgments

The authors are grateful for the financial support of NIH/ NCI R01CA140449 (JL), R01CA115483 (KSL), NIH/NCRR RR 1313461 and NIH/NCI 1R01CA155642 (PTH), Prostate Cancer Foundation (KSL), and the California Breast Cancer Research Program 14IB-0075 (PTH, TJ). The authors also thank the Center for Molecular and Genomic Imaging, UC Davis, for its imaging contributions, supported in part by a UC Davis Cancer Center support grant (P30CA093373, NCI).

Disclosures

The authors report no conflicts of interest in this work. KL is the founding scientist of LamnoTherapeutics Inc, which plans to develop the nanotherapeutics described in the manuscript.