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Delivery of therapeutic agents using nanoparticles
Uptake of fluorescent nanoparticles into macrophage cells. The nucleus (blue) was stained with Draq5, actin cytoskeleton (red) with Phalloidin Alexa Fluor 568 and the nanoparticles fluoresce green.
Certain drugs can be effectively targeted to specific cells in the body, such as cancer cells, by using polymeric nanoparticles to deliver them. The Cytometry Facility provided methods for testing encapsulation and drug delivery.
Encapsulation and drug delivery
Encapsulating paclitaxel, a commonly used anti-neoplastic agent, can promote an increase in bio-availability, protection from drug clearance, controlled drug release and reduction of systemic toxicity. Alisar Zahr (from Michael Pishko's group in the Department of Chemical Engineering) fabricated core-shell drug nanoparticles of paclitaxel and tested their anti-tumor activity in vitro with a breast carcinoma cell line. Confocal microscopy confirmed that particles were internalized and not just resident on the cell surface.
Clearance from the body
A major limitation of nanoparticle drug delivery is the time available for the drug to reach target cells before being removed from the body. Flow cytometry was used to determine how many nanoparticles were phagocytosed by white blood cell macrophages in vitro. Macrophages and fluorescent nanoparticles, prepared under a variety of experimental conditions, were incubated together. The number of live cells with and without nanoparticles could be easily determined. By testing a series of timepoints the extent of clearance by macrophages were quantitated.
Publications arising
- Zahr AS, Davis CA and Pishko MV (2006) Encapsulation of drug nanoparticles in self-assembled macromolecular nanoshells. Langmuir 22: 8178-8185
- Zahr AS and Pishko MV (2007) Encapsulation of Paclitaxel in macromolecular nanoshells. Biomacromolecules 8: 2004-2010.