(748e) Oil-In-Water Emulsion Based Fabrication of Biodegradable Prolate Spheroids (rods) for Drug Delivery

Authors: 
Heslinga, M. J., University of Michigan


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Biodegradable polymeric nanospheres have been widely suggested as injectable drug delivery vehicles as they are more likely than larger particles to clear the microcirculation.  Nevertheless, recent publications suggest that nano-sized particles exhibit minimal localization and adhesion to the blood vessel wall from bulk blood flow typical in large vessels.  Non-spherical particles may offer a higher likelihood of finding and binding to the blood vessel wall than spherical particles of the same volume due to the hydrodynamics of blood flow, leading to improved efficiency in the delivery of therapeutics to the vasculature. 

We previously showed that biodegradable poly(lactic-co-glycolic acid) (PLGA) prolate spheroids can be fabricated via oil-in-water (O/W) and water-in-oil-in-water (W/O/W) emulsion solvent evaporation.  We now demonstrate the flexibility of these fabrication methods to multiple biodegradable polymers and therapeutics.  In addition to particles made from PLGA, we fabricated prolate spheroid rods from poly(L-lactide-co-epsilon-caprolactone) (PLC) polymer.  Additionally, we now demonstrate that these techniques can encapsulate a wide range of therapeutics and imaging agents.  Encapsulated hydrophobic drugs include paclitaxel, lovastatin, and TNP-470, an analogue of fumagillin, while bovine serum albumin (BSA) was loaded as a hydrophilic drug.  For imaging, we demonstrate the capacity to fabricate spheroids loaded with fluorescein dye and iron oxide nanoparticles. We find that the release profile of loaded particles is geometry dependent by comparison of paclitaxel release from loaded spheroids and spheres of equivalent volumes at 37°C.