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

170 Citations (Scopus)

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

Fingerprint

Paclitaxel
Ovarian Neoplasms
Nanoparticles
Tumors
Micelles
Polyethylene glycols
Toxicity
Copolymers
Fluorescence
Cells
Tissue
Infrared radiation
Imaging techniques
Molecules
Acids
Pharmaceutical Preparations
Neoplasms
Cholic Acid
Maximum Tolerated Dose
Optical Imaging

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

Cite this

A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer. / Xiao, Kai; Luo, Juntao; Fowler, Wiley L.; Li, Yuanpei; Lee, Joyce S; Xing, Li; Cheng, R. Holland; Wang, Li; Lam, Kit.

In: Biomaterials, Vol. 30, No. 30, 10.2009, p. 6006-6016.

Research output: Contribution to journalArticle

Xiao, Kai ; Luo, Juntao ; Fowler, Wiley L. ; Li, Yuanpei ; Lee, Joyce S ; Xing, Li ; Cheng, R. Holland ; Wang, Li ; Lam, Kit. / A self-assembling nanoparticle for paclitaxel delivery in ovarian cancer. In: Biomaterials. 2009 ; Vol. 30, No. 30. pp. 6006-6016.
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