In vitro ultrasound-mediated leakage from phospholipid vesicles

Pong, Mona; Umchid, Sumet; Guarino, Andrew J.; Lewin, Peter A.; Litniewski, Jerzy; Nowicki, Andrzej; Wrenn, Steven P.

doi:10.1016/j.ultras.2006.07.021

Cited by 64 publications

(61 citation statements)

References 55 publications

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“…Variations in lipid membrane composition are shown to influence sonosensitivity of liposomes (Pong et al, 2006;Schroeder et al, 2009;Evjen et al, 2010a;Evjen et al, 2010b;Lin et al, 2001). We recently demonstrated that incorporation of DOPE into liposome bilayers drastically enhanced sonosensitivity compared to DSPE-based liposomes and standard liposomal DXR, respectively (Evjen et al, 2011a).…”

Section: Effect Of Dope Level On Sonosensitivitymentioning

confidence: 99%

“…Recently, there has been increasing interest in using ultrasound (US) as a means to physically and non-invasively trigger drug release from liposomes upon accumulation in tumour tissue (de Smet et al, 2010;Schroeder et al, 2009;Myhr and Moan, 2006;Pong et al, 2006). Local application of US to tumours produces several effects, such as enhancing extravasation of liposomes to tumours, inducing drug leakage from the liposome carrier and enhancing cell membrane permeability with a resulting increased intracellular drug uptake (For recent reviews see Schroeder et al, 2009;Pitt et al, 2004;Frenkel, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin

Evjen¹,

Hagtvet

Nilssen³

et al. 2011

European Journal of Pharmaceutical Sciences

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Ultrasound sensitive (sonosensitive liposomes) are drug delivery systems designed for releasing their drug load upon exposure to ultrasound (US). Inclusion of dioleoylphosphatidylethanolamine (DOPE) in liposome membranes was previously shown to induce sonosensitivity. For efficient US mediated drug delivery to solid tumours, a long blood circulation time of the liposomal drug providing high tumour uptake is required. In this study, blood pharmacokinetics of DOPE-based liposomal doxorubicin (DXR) were evaluated in mice. A markedly faster blood clearance of DXR was observed for DOPE-rich liposomes compared to Caelyx! (standard liposomal DXR). Subsequently, liposome membrane composition was altered to improve drug retention in the bloodstream, while maintaining sonosensitivity. Formulations with reduced blood clearance of DXR were obtained by reducing the content of DOPE from 62 to 32 or 25 mol%. These formulations showed long blood circulation time, as approximately 20% of the administered DXR dose was present in the bloodstream 24 h after intravenous injection. The reduction in liposomal DOPE content did not significantly reduce US mediated DXR release in vitro, indicating that DOPE is a potent modulator to sonosensitivity. The novel liposome formulations, containing moderate amounts of DOPE, displayed similar blood pharmacokinetic profiles as standard liposomal DXR, but a markedly improved sonosensitivity.

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Section: Effect Of Dope Level On Sonosensitivitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin

Evjen¹,

Hagtvet

Nilssen³

et al. 2011

European Journal of Pharmaceutical Sciences

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“…Researchers who have used similar devices to ours to study ultrasonically induced permeation have measured ultrasonic intensities in their devices using a hydrophone and reported values range from 0.03 to 3 W cm À2 . [34,37,43] While these intensities are higher than ultrasonic intensities used for diagnostic applications, they are certainly within the range of therapeutically accessible ultrasonic intensities. [34] G. D. Pangu, K. P. Davis, F. S. Bates, D. A.…”

Section: Discussionmentioning

confidence: 99%

“…A comparison of our results with the studies of ultrasonically induced leakage from liposomes reveals that the percentage leakage from polymer vesicles of similar sizes is comparable to that observed for liposomes. [41,43,44] However most of these studies with liposomes used sonication intervals of less than 10 min for their experiments. Also, a sonication cycle followed by an ultrasound-off period for fluorescence reading may have had a different effect on formation and growth of cavities than simultaneous measurement of fluorescent release during sonication.…”

Section: Discussionmentioning

confidence: 99%

“…[42] Studies have reported the dependence of liposomal permeabilization and release on sonication frequency, time, intensity, and liposome size with the general finding that the extent of release is higher at lower (<1 MHz) ultrasonic frequencies. [43,44] In this work, we assess the effect of low frequency ultrasound (20 kHz) on polymer vesicles formed from PEO-PBD copolymers. The permeabilization of vesicles is measured by loading a fluorescent molecule in aqueous core of the vesicles with another molecule that quenches its fluorescence.…”

Section: Introductionmentioning

confidence: 99%

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Ultrasonically Induced Release from Nanosized Polymer Vesicles

Pangu

Davis

Bates

et al. 2010

Macromolecular Bioscience

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Vesicles made from synthetic diblock copolymers, polymersomes, have great potential for targeted imaging and drug delivery. Ultrasound is gaining attention as a therapeutic tool in addition to its use in diagnostics. We report on the response of nanoscale vesicles made from PEO-b-PBD copolymers to ultrasound at 20 kHz. Leakage of a fluorescent dye from vesicle core was measured to study the permeation. Ultrasound causes significant leakage from the core above threshold intensity, suggesting that leakage is governed by acoustic cavitation. Size measurements and direct visualization of vesicles show that ultrasound does not completely rupture them into fragments but causes transient poration. The extent of leakage inversely depends on membrane thickness and directly depends on sonication time and intensity.

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Acoustically active liposome‐nanobubble complexes for enhanced ultrasonic imaging and ultrasound‐triggered drug delivery

Nguyen

Wrenn

2014

WIREs Nanomed Nanobiotechnol

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Ultrasound is well known as a safe, reliable imaging modality. A historical limitation of ultrasound, however, was its inability to resolve structures at length scales less than nominally 20 µm, which meant that classical ultrasound could not be used in applications such as echocardiography and angiogenesis where one requires the ability to image small blood vessels. The advent of ultrasound contrast agents, or microbubbles, removed this limitation and ushered in a new wave of enhanced ultrasound applications. In recent years, the microbubbles have been designed to achieve yet another application, namely ultrasound-triggered drug delivery. Ultrasound contrast agents are thus tantamount to 'theranostic' vehicles, meaning they can do both therapy (drug delivery) and imaging (diagnostics). The use of ultrasound contrast agents as drug delivery vehicles, however, is perhaps less than ideal when compared to traditional drug delivery vehicles (e.g., polymeric microcapsules and liposomes) which have greater drug carrying capacities. The drawback of the traditional drug delivery vehicles is that they are not naturally acoustically active and cannot be used for imaging. The notion of a theranostic vehicle is sufficiently intriguing that many attempts have been made in recent years to achieve a vehicle that combines the echogenicity of microbubbles with the drug carrying capacity of liposomes. The attempts can be classified into three categories, namely entrapping, tethering, and nesting. Of these, nesting is the newest-and perhaps the most promising.

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In vitro ultrasound-mediated leakage from phospholipid vesicles

Cited by 64 publications

References 55 publications

Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin

Sonosensitive dioleoylphosphatidylethanolamine-containing liposomes with prolonged blood circulation time of doxorubicin

Ultrasonically Induced Release from Nanosized Polymer Vesicles

Acoustically active liposome‐nanobubble complexes for enhanced ultrasonic imaging and ultrasound‐triggered drug delivery

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