Synergy between High Intensity Focused Ultrasound and Polypropylacrylic Acid in the Disruption of Membranes of Red Blood Cells

Abstract

The efficiency of therapeutic drugs is greatly reduced when they are administered systemically, while their potential for harm is distributed across the entire body. Synergistic relationships between high intensity focused ultrasound (HIFU) and agents of membrane disruption such as amphipathic polymers could selectively disrupt localized cell membranes and release bound chemical agents in the near vicinity to minimize side effects and increase the specificity of such agents. Human red blood cells were incubated with polypropylacrylic acid (PPAA) concentrations from 0.8 |J.g/ml to 1.6 p.g/ml, and then exposed to pulses o f high intensity focused ultrasound (HIFU) at intensities ranging from 572.68 W/cm2 to 1979.31 W/cm2. Release o f hemoglobin, a measure o f membrane disruption, was measured with UV spectrophotometry, and cavitation was quantified using LabView and MATLAB. Sham samples were run with no HIFU or no PPAA. Membrane disruption increased dramatically when both components were present. Polymer concentration did not appear to affect the extent of cavitation, while intensity of HIFU clearly was proportional to cell disruption. A synergistic effect was observed between these two agents, lending promise to the development of drug conjugation therapies.