|Wong, Ho - UNIVERSITY OF TORONTO|
|Rauth, Andrew - ONTARIO CANCER INSTITUTE|
|Bendayan, Reina - UNIVERSITY OF TORONTO|
|Manias, Janet - UNIVERSITY OF TORONTO|
|Ramaswamy, Manisha - UNIVERSITY OF TORONTO|
|Wu, Xiao - UNIVERSITY OF TORONTO|
Submitted to: Pharmaceutical Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 1, 2006
Publication Date: July 7, 2006
Citation: Wong, H.L., Rauth, A.M., Bendayan, R., Manias, J.L., Ramaswamy, M., Liu, Z., Erhan, S.Z., Wu, X.Y. 2006. A new polymer-lipid hybrid nanoparticle system increases cytotoxicity of doxorubicin against multidrug-resistant human breast cancer cells. Pharmaceutical Research. 23(7):1574-1585. Interpretive Summary: In this study we developed a new polymer from epoxidized soybean oil that can efficently load and release water-soluble anticancer drug doxorubicin hydrochloride (DOX) and enhances its efficacy against multidrug resistant breast cancer cells.
Technical Abstract: 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. Dox loaded nanoparticles (Dox-SLN) were prepared by dispersing a lipid with a complex of Dox and a new anionic polymer in water. Drug loading and release properties were measured spectrophotometrically. The in vitro cytotoxicity of Dox-SLN and the excipients in a MDR human breast cancer cell line (MDA435/LCC6/MDR1) and its wild-type line were evaluated by trypan blue exclusion and clonogenic assays. Dox-SLN 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. The new polymer-lipid hybrid nanoparticle system is effective for delivery of Dox and enhances its efficacy against MDR breast cancer cells.