A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer

Kai Xiao, Juntao Luo, Wiley L. Fowler, Yuanpei Li, Joyce S Lee, Li Xing, R. Holland Cheng, Li Wang, Kit Lam

Research output: Contribution to journalArticle

179 Scopus citations

Abstract

Paclitaxel (PTX) is one of the most effective chemotherapeutic drugs for the treatment of a variety of cancers. However, it is associated with serious side effects caused by PTX itself and the Cremophor EL emulsifier. In the present study, we report the development of a well-defined amphiphilic linear-dendritic copolymer (named as telodendrimer) composed of polyethylene glycol (PEG), cholic acid (CA, a facial amphiphilic molecule) and lysine, which can form drug-loaded core/shell micelles when mixed with hydrophobic drug, such as PTX, under aqueous condition. We have used PEG5k-CA8, a representive telodendrimer, to prepare paclitaxel-loaded nanoparticles (PTX-PEG5k-CA8 NPs) with high loading capacity (7.3 mg PTX/mL) and a size of 20-60 nm. This novel nanoformulation of PTX was found to exhibit similar in vitro cytotoxic activity against ovarian cancer cells as the free drug (Taxol®) or paclitaxel/human serum albumin nanoaggregate (Abraxane®). The maximum tolerated doses (MTDs) of PTX-PEG5k-CA8 NPs after single dose and five consecutive daily doses in mice were approximately 75 and 45 mg PTX/kg, respectively, which were 2.5-fold higher than those of Taxol®. In both subcutaneous and orthotopic intraperitoneal murine models of ovarian cancer, PTX-PEG5k-CA8 NPs achieved superior toxicity profiles and anti-tumor effects compared to Taxol® and Abraxane® at equivalent PTX doses, which were attributed to their preferential tumor accumulation, and deep penetration into tumor tissue, as confirmed by near infrared fluorescence (NIRF) imaging.

Original languageEnglish (US)
Pages (from-to)6006-6016
Number of pages11
JournalBiomaterials
Volume30
Issue number30
DOIs
StatePublished - Oct 2009

Keywords

  • Amphiphilic linear-dendritic copolymer
  • Biocompatibility
  • Chemotherapy
  • Drug delivery
  • Micelle
  • Ovarian cancer

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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  • Cite this

    Xiao, K., Luo, J., Fowler, W. L., Li, Y., Lee, J. S., Xing, L., Cheng, R. H., Wang, L., & Lam, K. (2009). A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer. Biomaterials, 30(30), 6006-6016. https://doi.org/10.1016/j.biomaterials.2009.07.015