Bursting Bubbles and Bilayers

Abstract

This paper discusses various interactions between ultrasound, phospholipid monolayer-coated gas bubbles, phospholipid bilayer vesicles, and cells. The paper begins with a review of microbubble physics models, developed to describe microbubble dynamic behavior in the presence of ultrasound, and follows this with a discussion of how such models can be used to predict inertial cavitation profiles. Predicted sensitivities of inertial cavitation to changes in the values of membrane properties, including surface tension, surface dilatational viscosity, and area expansion modulus, indicate that area expansion modulus exerts the greatest relative influence on inertial cavitation. Accordingly, the theoretical dependence of area expansion modulus on chemical composition - in particular, poly (ethylene glyclol) (PEG) - is reviewed, and predictions of inertial cavitation for different PEG molecular weights and compositions are compared with experiment. Noteworthy is the predicted dependence, or lack thereof, of inertial cavitation on PEG molecular weight and mole fraction. Specifically, inertial cavitation is predicted to be independent of PEG molecular weight and mole fraction in the so-called mushroom regime. In the “brush” regime, however, inertial cavitation is predicted to increase with PEG mole fraction but to decrease (to the inverse 3/5 power) with PEG molecular weight. While excellent agreement between experiment and theory can be achieved, it is shown that the calculated inertial cavitation profiles depend strongly on the criterion used to predict inertial cavitation. This is followed by a discussion of nesting microbubbles inside the aqueous core of microcapsules and how this significantly increases the inertial cavitation threshold. Nesting thus offers a means for avoiding unwanted inertial cavitation and cell death during imaging and other applications such as sonoporation. A review of putative sonoporation mechanisms is then presented, including those involving microbubbles to deliver cargo into a cell, and those - not necessarily involving microubbles - to release cargo from a phospholipid vesicle (or reverse sonoporation). It is shown that the rate of (reverse) sonoporation from liposomes correlates with phospholipid bilayer phase behavior, liquid-disordered phases giving appreciably faster release than liquid-ordered phases. Moreover, liquid-disordered phases exhibit evidence of two release mechanisms, which are described well mathematically by enhanced diffusion (possibly via dilation of membrane phospholipids) and irreversible membrane disruption, whereas liquid-ordered phases are described by a single mechanism, which has yet to be positively identified. The ability to tune release kinetics with bilayer composition makes reverse sonoporation of phospholipid vesicles a promising methodology for controlled drug delivery. Moreover, nesting of microbubbles inside vesicles constitutes a truly “theranostic” vehicle, one that can be used for both long-lasting, safe imaging and for controlled drug delivery.

High intensity focused ultrasound (HIFU) applied to hepato-bilio-pancreatic and the digestive system—current state of the art and future perspectives

“…HIFU can achieve a spectacular decrease of cancer-related pain and could complement or even replace opioids and plexus neurolysis. The mechanical effect of HIFU seems to induce neuromodulation and pain relief through a reversible block of nerve activity (85). Different considerations have to be HIFU, high intensity focused ultrasound.…”

Perfluoroalkylated poly(oxyethylene) thiols: Synthesis, adsorption dynamics and surface activity at the air/water interface, and bubble stabilization behaviour

“…Water was purified using a Millipore system (surface tension: 72.1 mN m À1 at 20 8C, resistivity: 18.2 MV cm). 1 H, 13 C, and 19 F NMR spectra were recorded in CDCl 3 with a Bruker AM 400 spectrometer. Chemical shifts are reported in parts per million (d in ppm) relative to Me 4 Si ( 1 H, 13 C) and CFCl 3 ( 19 F).…”

“…The same procedure applied to the synthesis of the other F-alkyl POE thiols gave the following overall yields: n = 4, y = 4: $15%; n = 4, y = 6: $20%; n = 6, y = 6: $15%. All the final compounds were characterized by 1 H, 13 …”

“…Gas microbubbles are, for example, promising theranostic agents susceptible to crossing physiological barriers with limited damage under focalized application of ultrasound [10][11][12]. Shell film viscosity and elasticity, and hence, shell composition, determine the inertial cavitation threshold so as to either achieve or avoid cavitation at a given operating pressure [13,14]. Control of surfactant film elasticity is therefore highly desirable.…”

Ultrasound triggered drug delivery with liposomal nested microbubbles

“…In this case, poration of the membrane facilitates release of the drug from the liposome to a nearby structure, which we refer to as reverse sonoporation. In reverse sonoporation, the direction of transport and perhaps also the mechanism of poration is different than traditional sonoporation [18]. Using focused ultrasound, only the desired region within the focal zone of the transducer will receive enough energy to release the drug, reducing systemic side effects.…”