(135b) Cell Uptake of Morphologically Distinct Polymer Micelles
AIChE Annual Meeting
2008
2008 Annual Meeting
Materials Engineering and Sciences Division
Biomaterials for Drug Delivery I
Monday, November 17, 2008 - 3:35pm to 3:55pm
Polymer based micelles show considerable promise as drug delivery systems, with some already in clinical trials, but all of them possess spherical morphology. Cylindrical worm-like micelles seem to possess several advantages over spherical micelles, particularly longer blood circulation and higher drug loading capacity (1,2). Although in vitro and in vivo studies of worm-like micelle have demonstrated efficiency in the delivery of anti-cancer drug, little is known as to how cells internalize worm-like micelles. Detailed understanding of the cell uptake mechanism and subsequent intracellular trafficking of worm-like micelles could be helpful for development of worm-like micelles; for example, a single microns-long micelle carries enough drug to kill a single cell whereas hundreds of micelles would be required to deliver an equivalent dose. In the present work, both worm-like and spherical micelles are prepared from amphiphilic diblock copolymer poly(ethylene oxide)-b-poly(ε-caprolactone) (OCL), a bio-compatible copolymer. The volume fraction of the poly(ethylene oxide) segment determines the preferred morphology upon assembly in aqueous media (3), although sonication and other disruptive treatments can generate kinetically stable sphere micelles regardless of preferred morphology. OCL-based micelles are visualized by integration of fluorescent dyes and fluorescence microscopy used to visualize intracellular localization as a function of time in culture with human lung carcinoma cell A549. Current studies suggest that worm-like micelles are scissioned as they are internalized by cells, highlighting the strength of the fission machinery in internalization.
[Reference]
1. Geng et al. Nature Nanotechnology 2, 249-255 (2007)
2. Cai et al. Pharmaceutical Research 24, 2099-2109 (2007)
3. Discher et al. Annu, Rev. Biomed. Eng. 8, 323-341 (2006)