Mar 1, 2011
Doxorubicin-loaded micelles increase drug activity and lower systemic toxicity
Doxorubicin loaded MPEG-PCL (Dox/MPEG-PCL) micelles have been readily prepared by a self-assembly method. The incorporation of doxorubicin in MPEG-PCL micelles enhanced the anticancer activity of the active ingredient and decreased its systemic toxicity compared with free Dox. The development team hopes that the Dox/MPEG-PCL micelles could lead to potential clinical applications in cancer therapy.
MaLing Gou and colleagues from the Nano-biomaterials research group at Sichuan University readily prepared Dox/MPEG-PCL micelles by a novel self-assembly method. The technique involves heating an MPEG-PCL aqueous slurry to 50 °C and then incorporating Dox into MPEG-PCL micelles through a pH-induced self-assembly method. The team believes that this self-assembly method may be one of the easiest ways to prepare Dox-loaded polymeric nanoparticles/micelles in the literature.
Dox/MPEG-PCL micelles with a drug loading of 4.2% were monodisperse and ∼20 nm in diameter. Compared with free Dox, the Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Furthermore, these Dox/MPEG-PCL micelles induced lower systemic toxicity than free Dox.
The researchers also examined the extravasation of Dox and MPEG-PCL micelle-encapsulated Dox from vessels to surrounding spaces in vivo in a transgenetic zebrafish model. Taking advantage of the transparency of the zebrafish larva and the visual contrast between Dox and EGFP-exp host endothelial cells, this in vivo analysis was carried out in real time.
The group found that encapsulation of Dox in MPEG-PCL micelles slowed the extravasation of Dox (see images above), which may be one of the reasons for the reduced systemic toxicity of Dox/MPEGPCL micelle treatment, compared with free Dox treatment.
Full results can be found in the journal Nanotechnology.
About the author
This study was conducted by the Nano-biomaterials research group, which is part of the State Key Laboratory of Biotherapy at Sichuan University in Chengdu, China. The team is led by Prof. Zhiyong Qian, who is associate editor of two international journals – J. Biomed Nanotechnology and Advanced Science Letters. His research interest is focused on advanced drug-delivery systems, including nanobiotechnology, thermo- and pH-sensitive hydrogels, non-viral gene vectors, as well as other systems. This work was mainly performed by MaLing Gou, PhD, who is an assistant professor at the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University. Gou's research involves using nanotechnology to improve cancer treatment.