Coencapsulation of lipid microbubbles within polymer microcapsules for contrast applications

Dicker, Stephen; Mleczko, Michal J.; Hensel, Karin; Bartolomeo, Antonio Di; Schmitz, Georg; Wrenn, Steven P.

doi:10.1179/1758897911y.0000000002

Cited by 10 publications

(10 citation statements)

References 24 publications

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“…It appears that two regimes exist with a threshold between 1.3 and 2.1 MPa. Observations of thresholds associated with cavitation-induced biologic effects and other ultrasonic phenomena are not unusual and are very well documented [18,28,[39][40][41]. For the purpose of this study, it has been confirmed that at the lowest peak negative pressure (PNP = 0.54 MPa) 0.52 ± 6% of the sample is inertially cavitating and at the highest pressure (PNP = 3.7 MPa) 36 ± 6% of the sample is inertially cavitating.…”

Section: Discussionsupporting

confidence: 68%

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Ultrasound triggered drug delivery with liposomal nested microbubbles

Wallace

Wrenn

2015

Ultrasonics

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When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa).

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Section: Discussionsupporting

confidence: 68%

“…Microbubbles were prepared as described previously [19]. Lipid film solutions of 95 mol% DSPC in chloroform and 5 mol% DSPE-PEG3000 in chloroform both with a concentration of 25 mg/mL, were mixed together in a 20 mL scintillation vial and spin dried under a stream of nitrogen for 15 min or until the chloroform had evaporated.…”

Section: Microbubble Formationmentioning

confidence: 99%

Ultrasound triggered drug delivery with liposomal nested microbubbles

Wallace

Wrenn

2015

Ultrasonics

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“…Microbubbles were prepared as described previously [29]. Lipid film solutions of 95 mol% DSPC in chloroform and 5 mol% DSPE-PEG3000 in chloroform both with a concentration of 25 mg/mL, were mixed together and spin dried under a constant flow of nitrogen to ensure a uniform film on the bottom of the vial.…”

Section: Microbubble Formationmentioning

confidence: 99%

“…For example, when microbubbles are nested within the aqueous interior of a poly-lactic acid (PLA) shell, the destruction of microbubbles at 1 MPa decreases from 70% to 20% [29]. PLA allows for greater stability of the contrast agent within the body and is already approved by the FDA for several in vivo applications, such as medical implants [22].…”

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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“…In particular, microbubbles are co-encapsulated with drugs inside a vesicle or microcapsule where the drug has little-to-no (side) effect. Drug is released on command using ultrasound as a remote-mechanical trigger to induce inertial cavitation of the microbubbles; the ensuing shock wave then cracks the microcapsule (or forms pores in the vesicle) shell 43, 44…”

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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Coencapsulation of lipid microbubbles within polymer microcapsules for contrast applications

Cited by 10 publications

References 24 publications

Ultrasound triggered drug delivery with liposomal nested microbubbles

Ultrasound triggered drug delivery with liposomal nested microbubbles

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

Bursting Bubbles and Bilayers

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