Tuesday, 24 May 2005

This presentation is part of: Polymeric Biomaterials Posters

Amphiphilic-scoripion like macromolecules (AScMs): efficient carriers for intracellular drug delivery

Jelena Djordjevic, Rutgers University, Piscataway, NJ and Kathryn E. Uhrich, Rutgers University, Piscataway, NJ.

Amphiphilic scorpion-like macromolecules (AScMs) are biodegradable, non-toxic and non-immunogenic block copolymers that form micelles above their CMC (~ 10-7 M). The purpose of this study was to demonstrate and characterize uptake and intracellular retention of AScMs in vitro using human umbilical vein endothelial cells (HUVEC). Briefly, uptake studies were performed by monitoring cellular accumulation of the fluorescent dye-loaded AScMs (R110 and R123, respectively) as a function of time (15-240 min) and AScMs concentration (0.00011 mM); intracellular distribution and localization of dye-loaded AScMs in HUVEC was investigated using confocal microscope. In addition, intracellular localization of AScMs was confirmed using transmission electron microscopy studies. The uptake of R110- and R123-loaded AScMs was found to decrease with an increase in the AScMs concentration; the decreased accumulation of R110- and R123-loaded AScMs in HUVEC monolayers was inversely correlated with the extent of dyes partitioning into AScMs. In addition, uptake of R110- and R123-loaded micelles was found to be time-dependent; the uptake was seen as early as at 15 min and peaked within 60 min of experiment. Furthermore, confocal microscopy studies demonstrated increased fluorescence activity in the cells with increase in the incubation time, whereas TEM studies confirmed presence of AScMs within the cellular compartments. In conclusion, AScMs were shown to be rapidly internalized into the HUVEC; cellular uptake was shown to be time- and AScMs concentration-dependent, and the micelles were mainly localized in the cytoplasm. Thus, AScMs are useful for localizing therapeutic compounds or genes into endothelial cells to achieve a sustained therapeutic effect.

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