Equilibrium loading of cells with macromolecules by ultrasound:: Effects of molecular size and acoustic energy

Ultrasound has been shown to deliver small compounds, macromolecules, and DNA into cells, which suggests potential applications in drug and gene delivery. However, the effect of molecular size on intracellular uptake has not been quantified. This study measured the effect of molecule size (calcein, 623 Da; bovine serum albumin, 66 kDa; and two dextrans, 42 and 464 kDa) on molecular uptake and cell viability in DU145 prostate cancer cells exposed to 500 kHz ultrasound. Molecular uptake in viable cells was shown to be very similar for small molecules and macromolecules and found to correlate with acoustic energy exposure. Molecular uptake was seen to be heterogeneous among viable cells exposed to the same ultrasound conditions; this heterogeneity also correlated with acoustic energy exposure. In a fraction of these cells, molecular uptake reached thermodynamic equilibrium with the extracellular solution for the small molecule and all three macromolecules. The results demonstrate that ultrasound provides a means to load viable cells with large numbers of macromolecules, which may be of use for laboratory and possible clinical drug delivery applications. (C) 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.