Effect of biomimetic shear stress on intracellular uptake and cell-killing efficiency of doxorubicin in a free and liposomal formulation

Abstract

Shear stress could be considered in the context of cellular uptake and cell-killing efficiency. Thus, mimicking the dynamic characteristics of in vivo environment is important in targeted drug delivery. We investigated the intracellular uptake and cell-killing efficiency of doxorubicin (DOX) in a free and liposomal form (Doxil(®)) under biomimetic shear stress to mimic in vivo environment. In this dynamic environment, cells demonstrated significantly higher fluorescence intensity than that of the static environment, and fluorescence microscopy images indicated increased intracellular uptake of DOX in the presence of fluidic shear stress. In cells treated with free DOX and liposomal Doxil(®), cell-killing efficiency was affected by shear stress. Taken together, shear stress, affecting drug uptake and cell-killing efficiency, is important in intracellular drug targeting.

Keywords: Biomimetic dynamic conditions; Cell microenvironment; Cell-killing efficiency; Cellular drug delivery; Doxorubicin; Liposomal formulation; Shear stress.