Phospholipid-stabilized microbubbles: Influence of shell chemistry on cavitation threshold and binding to giant uni-lamellar vesicles

Wrenn, Steven P.; Mleczko, Michal J.; Schmitz, Georg

doi:10.1016/j.apacoust.2008.09.017

Cited by 28 publications

(13 citation statements)

References 61 publications

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“…The measured stiffness could assist in both the theoretical modeling and experimental studies of the mechanical stresses induced on the blood vessel walls, allowing more precise understanding of the microbubble interactions with the capillaries. The slight change of the physicochemical properties of the microbubble shell was believed to cause a direct effect on the mechanical characteristics [41], [51]. The general assumption of no structural variation of the microbubble shells typically made in theoretical modeling [17], [34] may not hold for lipid microbubbles because our results indicated that microstructures on the monolayer surface could influence the overall microbubble elasticity.…”

Section: Discussionmentioning

confidence: 91%

An experimental study on the stiffness of size-isolated microbubbles using atomic force microscopy

Chen

Finan

et al. 2013

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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To fully assess contrast-enhanced acoustic bioeffects in diagnostic and therapeutic procedures, the mechanical properties of microbubbles need to be considered. In the present study, direct measurements of the microbubble stiffness were performed using atomic force microscopy by applying nanoscale compressions (up to 25 nN/s) on size-isolated, lipid-coated microbubbles (diameter ranges of 4 to 6 μm and 6 to 8 μm). The stiffness was found to lie between 4 and 22 mN/m and to decrease exponentially with the microbubble size within the diameter range investigated. No cantilever spring constant effect was found on the measured stiffness. The Young’s modulus of the size-isolated microbubbles used in our study ranged between 0.4 and 2 MPa. Microstructures on the surface of the microbubbles were found to influence the overall microbubble elasticity. Our results indicated that more detailed theoretical models are needed to account for the size-dependent microbubble mechanical properties to accurately predict their acoustic behavior. The findings provided useful insights into guidance of cavitation-induced drug and gene delivery and could be used as part of the framework in studies on the shear stresses induced on the blood vessel walls by oscillating microbubbles.

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Section: Discussionmentioning

confidence: 91%

An experimental study on the stiffness of size-isolated microbubbles using atomic force microscopy

Chen

Finan

et al. 2013

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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“…Early UCAs, now considered first-generation agents, comprised air plus a shell of albumin, lipid, or acrylate; second-generation agents replaced air with heavier, fluorinated compounds (e.g., octafluoropropane, perfluorobutane, or sulfur hexafluoride) that dissolve more slowly; and third-generation agents incorporated additional species (e.g., charged surfactants or PEGylated lipids) into the stabilizing shell to prevent bubble coalescence and convey stealth quality so as to prolong circulation time 3. It is now appreciated that a phospholipid monolayer coating provides reasonable longevity without sacrificing too greatly the acoustic response, and the fact that phospholipid composition and microstructure can influence microbubble material properties and resulting acoustic phenomena is widely recognized 4-9…”

Section: Inertial Cavitationmentioning

confidence: 99%

Bursting Bubbles and Bilayers

Wrenn¹,

Dicker²,

Small³

et al. 2012

Theranostics

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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.

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“…The key mechanism for this effect is believed to be inertial cavitation. Although controlled inertial cavitation can be used for therapeutics, the local increase in temperature and pressure of up to 5000 K [14] and 100 MPa [15], respectively, can damage nearby microstructures, including cells [16][17][18]. For this reason microbubble contrast agents have come under scrutiny since their development [19].…”

Section: Introductionmentioning

confidence: 99%

Influence of nesting shell size on brightness longevity and resistance to ultrasound-induced dissolution during enhanced B-mode contrast imaging

et al. 2014

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Phospholipid-stabilized microbubbles: Influence of shell chemistry on cavitation threshold and binding to giant uni-lamellar vesicles

Cited by 28 publications

References 61 publications

An experimental study on the stiffness of size-isolated microbubbles using atomic force microscopy

An experimental study on the stiffness of size-isolated microbubbles using atomic force microscopy

Bursting Bubbles and Bilayers

Influence of nesting shell size on brightness longevity and resistance to ultrasound-induced dissolution during enhanced B-mode contrast imaging

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