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Investigating the role of lipid transfer in sonoporation

The permeabilisation of cell membranes following exposure to microbubbles and ultrasound has considerable potential for therapeutic delivery. Recent studies have demonstrated that transfer of material takes place between phospholipid-coated microbubbles and cell membranes. The aim of this study was to investigate the impact of this transfer on membrane properties and cell permeability. Microbubbles were prepared with matched concentrations and size distributions from a series of formulations utilising phospholipids with differing molecular characteristics. Quantitative fluorescence microscopy techniques were used to quantify changes in the molecular packing, viscosity, and permeability to model drugs of cancer cells under mild ultrasound exposure (15 s of 1 MHz centre frequency, 125 kPa peak negative pressure, 1 kHz pulse repetition frequency, and 10% duty cycle). The molecular “packing” of cancer cell membranes was found to be significantly affected by the transfer of both phospholipids and other microbubble coating constituents. This was particularly pronounced in the case of microbubbles containing a specific class of lipids, which promoted a ~4-fold increase in model drug uptake following ultrasound exposure. Similar results were observed in an investigation of permeability in an in vitro blood brain barrier model suggesting that microbubble composition may play a key role in the efficacy of ultrasound mediated delivery.