The efficacy of a
drug is dependent on its mode of delivery and its potency at the
tumor site. In this study, the
drug delivery and efficacy of
silk fibroin coated
liposomes (SF-ELP), encapsulating a
receptor tyrosine kinase inhibitor,
emodin, on Her2/neu over-expressing
breast cancer cells, was investigated. This study demonstrates that SF-ELP was more efficacious in suppressing the growth of Her2/neu over-expressing
breast cancer cells MDA-MB-453 and BT-474 as compared to uncoated
emodin loaded
liposomes (ELP). Reduced levels of phosphorylated Her2/neu correlated with growth inhibition observed in the MDA-MB-453 cells, treated with both ELP and SF-ELP. ELP treatment of MDA-MB-453
breast cancer cells resulted in inhibition of the PI3K pathway whereas SF-ELP treatment inhibited both the PI3K and MAPK pathways, which contributed to the enhanced growth inhibitory effects of Her2/neu over-expressing
breast cancer cells. Coating of ELP with
silk fibroin did not alter the target specificity of
emodin, on the other hand the
emodin efficacy was enhanced. Higher uptake of
emodin delivered by SF-ELP lead to increased cell death as compared to
emodin delivery via ELP.
Silk fibroin coating around the
liposome imparts an extra layer that
emodin has to extravasate in order to release from the encapsulating
liposome. This increases retention of the
drug in the cell for a longer time and protects
emodin from quick release and metabolism. Longer intracellular retention may lead to the longer availability of
emodin for down-modulation of various Her2/neu pathways. This study demonstrates that
silk fibroin coating enhanced
emodin delivery in Her2/neu over-expressing
breast cancer cells thereby increasing the overall efficacy of the
drug.