Pharmaceutical Research

, Volume 23, Issue 7, pp 1574–1585

A New Polymer–Lipid Hybrid Nanoparticle System Increases Cytotoxicity of Doxorubicin Against Multidrug-Resistant Human Breast Cancer Cells

  • Ho Lun Wong
  • Andrew M. Rauth
  • Reina Bendayan
  • Janet L. Manias
  • Manisha Ramaswamy
  • Zengshe Liu
  • Sevim Z. Erhan
  • Xiao Yu Wu
Research Paper

DOI: 10.1007/s11095-006-0282-x

Cite this article as:
Wong, H.L., Rauth, A.M., Bendayan, R. et al. Pharm Res (2006) 23: 1574. doi:10.1007/s11095-006-0282-x

Purpose

This work is intended to develop and evaluate a new polymer–lipid hybrid nanoparticle system that can efficiently load and release water-soluble anticancer drug doxorubicin hydrochloride (Dox) and enhance Dox toxicity against multidrug-resistant (MDR) cancer cells.

Methods

Cationic Dox was complexed with a new soybean-oil-based anionic polymer and dispersed together with a lipid in water to form Dox-loaded solid lipid nanoparticles (Dox–SLNs). Drug loading and release properties were measured spectrophotometrically. The in vitro cytotoxicity of Dox–SLN and the excipients in an MDR human breast cancer cell line (MDA435/LCC6/MDR1) and its wild-type line were evaluated by trypan blue exclusion and clonogenic assays. Cellular uptake and retention of Dox were determined with a microplate fluorometer.

Results

Dox–SLNs were prepared with a drug encapsulation efficiency of 60–80% and a particle size range of 80–350 nm. About 50% of the loaded drug was released in the first few hours and an additional 10–20% in 2 weeks. Treatment of the MDR cells with Dox–SLN resulted in over 8-fold increase in cell kill when compared to Dox solution treatment at equivalent doses. The blank SLN and the excipients exhibited little cytotoxicity. The biological activity of the released Dox remained unchanged from fresh, free Dox. Cellular Dox uptake and retention by the MDR cells were both significantly enhanced (p < 0.05) when Dox was delivered in Dox–SLN form.

Conclusions

The new polymer–lipid hybrid nanoparticle system is effective for delivery of Dox and enhances its efficacy against MDR breast cancer cells.

Key Words

breast cancer cells doxorubicin delivery in vitro cytotoxicity multidrug resistance polymer–lipid hybrid nanoparticles 

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Ho Lun Wong
    • 1
  • Andrew M. Rauth
    • 2
  • Reina Bendayan
    • 1
  • Janet L. Manias
    • 1
  • Manisha Ramaswamy
    • 1
  • Zengshe Liu
    • 3
  • Sevim Z. Erhan
    • 3
  • Xiao Yu Wu
    • 1
  1. 1.Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoCanada
  2. 2.Ontario Cancer InstituteTorontoCanada
  3. 3.Food and Industrial Oil ResearchUSDA/ARS/NCAURPeoriaUSA