Acoustic vaporization threshold of lipid-coated perfluoropentane droplets

Aliabouzar, Mitra; Kumar, Krishna N.; Sarkar, Kausik

doi:10.1121/1.5027817

Cited by 32 publications

(31 citation statements)

References 55 publications

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“…Using larger micrometer-sized PFC droplets, an early report showed that the activation threshold decreased when the agents were exposed to US pulses of increased frequency (Kripfgans et al, 2004). A similar trend in PCCA activation thresholds was found when using smaller PFC-based nanodroplets (Aliabouzar et al, 2018;Sheeran et al, 2013;Sheeran et al, 2016), which agreed with our findings and what nucleation therapy predicts. Several studies have also demonstrated that PCCA activation thresholds are considerably reduced when using larger PCCAs (Kripfgans et al, 2004;Miles et al, 2016;Schad and Hynynen, 2010;Shpak et al, 2014), going from room to body temperatures (Schad and Hynynen, 2010;Williams et al, 2013), or by incorporating PFC compounds with lower boiling points during PCCA formulation (de Gracia Lux et al, 2017;Matsunaga et al, 2012;Sheeran et al, 2011).…”

Section: Figsupporting

confidence: 91%

“…In the presence of US wave energy, this nanodroplet vaporization process occurs beyond a critical peak negative pressure, which is called the vaporization or activation threshold. Importantly, the activation threshold depends on the properties of the nanodroplet PFC liquid core and phospholipid coating, ambient conditions, and US excitation parameters (Aliabouzar et al, 2018;Hoyt et al, 2016;Kripfgans et al, 2004;Martz et al, 2011;Sheeran et al, 2012;Shpak et al, 2014).…”

Section: Theorymentioning

confidence: 99%

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Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Raut

Khairalseed

Honari

et al. 2019

The Journal of the Acoustical Society of America

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A phase-change contrast agent (PCCA) can be activated from a liquid (nanodroplet) state using pulsed ultrasound (US) energy to form a larger highly echogenic microbubble (MB). PCCA activation is dependent on the ambient pressure of the surrounding media, so any increase in hydrostatic pressure demands higher US energies to phase transition. In this paper, the authors explore this basic relationship as a potential direction for noninvasive pressure measurement and foundation of a unique technology the authors are developing termed tumor interstitial pressure estimation using ultrasound (TIPE-US). TIPE-US was developed using a programmable US research scanner. A custom scan sequence interleaved pulsed US transmissions for both PCCA activation and detection. An automated US pressure sweep was applied, and US images were acquired at each increment. Various hydrostatic pressures were applied to PCCA samples. Pressurized samples were imaged using the TIPE-US system. The activation threshold required to convert PCCA from the liquid to gaseous state was recorded for various US and PCCA conditions. Given the relationship between the hydrostatic pressure applied to the PCCA and US energy needed for activation, phase transition can be used as a surrogate of hydrostatic pressure. Consistent with theoretical predictions, the PCCA activation threshold was lowered with increasing sample temperature and by decreasing the frequency of US exposure, but it was not impacted by PCCA concentration.

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Section: Figsupporting

confidence: 91%

Section: Theorymentioning

confidence: 99%

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Raut

Khairalseed

Honari

et al. 2019

The Journal of the Acoustical Society of America

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“…The lung surfactant nanodrops formed in this study did not spontaneously vaporize at physiological temperature or at very low ultrasound MIs, but rather vaporized in a controllable manner at MIs suitable for diagnostic imaging and therapeutic applications. The implementation of the three different ultrasound systems operating at different transmit frequencies indicate that MI was a suitable parameter to control to initiate ADV, although prior literature has shown inconsistent effects of frequency and pressure on nanodrop ADV [27]. This is an important result illustrating the ability for lung surfactant nanodrops to be rapidly translated to the clinic.…”

Section: Resultsmentioning

confidence: 97%

Contrast-enhanced sonography with biomimetic lung surfactant nanodrops

Thomas

Song

Upadhyay

et al. 2020

Preprint

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Nanodrops comprising a perfluorocarbon liquid core can be acoustically vaporized into echogenic microbubbles for ultrasound imaging. Packaging the microbubble in its condensed liquid state provides distinct advantages, including in situ activation of the acoustic signal, longer circulation persistence, and the advent of expanded diagnostic and therapeutic applications in pathologies which exhibit compromised vasculature. One obstacle to clinical translation is the inability of the limited surfactant present on the nanodrop to encapsulate the greatly expanded microbubble interface, resulting in ephemeral microbubbles with limited utility. In this study, we examine a biomimetic approach to stabilizing an expanding gas surface by employing the lung surfactant replacement, Beractant. Lung surfactant contains a suite of lipids and surfactant proteins that provides efficient shuttling of material from bilayer folds to the monolayer surface. We therefore hypothesized that Beractant would improve stability of acoustically vaporized microbubbles. To test this hypothesis, we characterized Beractant surface dilation mechanics and revealed a novel biophysical phenomenon of rapid interfacial melting, spreading and re-solidification. We then harnessed this unique spreading capability to increase the stability and echogenicity of microbubbles produced after acoustic droplet vaporization for in vivo ultrasound imaging. Such biomimetic lung surfactant-stabilized nanodrops may be useful for applications in ultrasound imaging and therapy.

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“…Intermediate response resulting from the presence of the nanoemulsion near the liposomes is influencing drug release, possibly by enhanced energy transfer to the lipid bilayer that can deform or disrupt the bilayer. The phase transition of PFC from liquid to gas, which is in the range of 1 to 10 MPa (Aliabouzar et al, 2018), and the resulting expansion seems a plausible mechanism for the more efficient payload release. Thermal effects can be excluded since the maximum temperature increase upon HIFU exposure did not exceed 2 degrees (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Ultrasound-Sensitive Liposomes for Triggered Macromolecular Drug Delivery: Formulation and In Vitro Characterization

et al. 2019

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Mistletoe lectin-1 (ML1) is a nature-derived macromolecular cytotoxin that potently induces apoptosis in target cells. Non-specific cytotoxicity to normal cells is one of the major risks in its clinical application, and we therefore propose to encapsulate ML1 in a nanocarrier that can specifically release its cargo intratumorally, thus improving the efficacy to toxicity ratio of the cytotoxin. We investigated the encapsulation of ML1 in ultrasound-sensitive liposomes (USL) and studied its release by high-intensity focused ultrasound (HAccessedIFU). USL were prepared by entrapment of perfluorocarbon nanodroplets in pegylated liposomes. The liposomes were prepared with different DPPC/cholesterol/DSPE-PEG2000 lipid molar ratios (60/20/20 for USL20; 60/30/10 for USL10; 65/30/5 for USL5) before combination with perfluorocarbon (PFC) nanoemulsions (composed of DPPC and perfluoropentane). When triggered with HIFU (peak negative pressure, 2–24 MPa; frequency, 1.3 MHz), PFC nanodroplets can undergo phase transition from liquid to gas thus rupturing the lipid bilayer of usl. Small unilamellar liposomes were obtained with appropriate polydispersity and stability. ML1 and the model protein horseradish peroxidase (HRP) were co-encapsulated with the PFC nanodroplets in USL, with 3% and 7% encapsulation efficiency for USL20 and USL10/USL5, respectively. Acoustic characterization experiments indicated that release is induced by cavitation. HIFU-triggered release of HRP from USL was investigated for optimization of liposomal composition and resulted in 80% triggered release for USL with USL10 (60/30/10) lipid composition. ML1 release from the final USL10 composition was also 80%. Given its high stability, suitable release, and ultrasound sensitivity, USL10 encapsulating ML1 was further used to study released ML1 bioactivity against murine CT26 colon carcinoma cells. Confocal live-cell imaging demonstrated its functional activity regarding the interaction with the target cells. We furthermore demonstrated the cytotoxicity of the released ML1 (I.E., After USL were treated with HIFU). The potent cytotoxicity (IC50 400 ng/ml; free ML1 IC50 345 ng/ml) was compared to non-triggered USL loaded with ML1. Our study shows that USL in combination with HIFU hold promise as trigger-sensitive nanomedicines for local delivery of macromolecular cytotoxins.

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Acoustic vaporization threshold of lipid-coated perfluoropentane droplets

Cited by 32 publications

References 55 publications

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

Contrast-enhanced sonography with biomimetic lung surfactant nanodrops

Ultrasound-Sensitive Liposomes for Triggered Macromolecular Drug Delivery: Formulation and In Vitro Characterization

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