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Core-Shell Drug Nanoparticles for Therapeutic Delivery

Alisar S. Zahr, Chemical Engineering, The Pennsylvania State Univeristy, 263 MRL, Hastings Rd, University Park, PA 16802 and Michael V. Pishko, Department of Chemical Engineering, The Pennsylvania State University, 104 Fenske Laboratory, University Park, PA 16802-4400.

A layer-by-layer (LbL) self-assembly technique was used to encapsulate core charged drug nanoparticles in a polymeric nanoshell. This approach provides a new strategy in the development of polymeric vehicles in controlling drug release and targeting to diseased tissues and cells specific to a human illness, such as cancer. Core paclitaxel nanoparticles were fabricated by a modified solvent-evaporation technique to yield nanoparticles with an average size of 150 nm. A nanoshell composed of multilayered polyelectrolytes, poly-L-lysine and heparan sulfate, was assembled step wise onto core charged drug nanoparticles. The presence of each adsorbed layer was confirmed by zeta potential measurements. Also, transmission electron microscopy was utilized to confirm the successful encapsulation of core paclitaxel nanoparticles within a nanoshell with approximate thickness of 10 nm.

An in vitro cytotoxic assay was performed by incubating core-shell nanoparticles of paclitaxel with breast cancer cells, MCF-7, for 24 and 48 hours. Results illustrated that paclitaxel nanoparticles arrested MCF-7 cells in the G2/M phase, which agreed with results in literature. These results were also compared to the standard method of delivery; paclitaxel dissolved in Cremophor EL and dehydrated ethanol. Confocal microscopy confirmed that the paclitaxel core-shell nanoparticles induced apoptosis and necrosis of MCF-7 cells after 24 hours at low and high concentrations, respectively. The results suggest that paclitaxel core-shell nanoparticles suspended in a buffered solution provides an alternative mode of delivery that may increase efficacy by decreasing systemic toxicity.