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Liu, Jin; Lewis, Thomas N.; Prausnitz, Mark R.

doi:10.1023/a:1011984817567

Cited by 132 publications

(18 citation statements)

References 18 publications

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“…It is well accepted that ultrasonic energy above a threshold readily generates heat, which may be detrimental to cell health [36]. The cellular response to an ultrasound-driven increase in localised temperature has not been extensively evaluated for long-term effects [34].…”

Section: Discussionmentioning

confidence: 99%

Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina

et al. 2017

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Herein we showcase the potential of ultrasound-responsive nanobubbles in enhancing macromolecular permeation through layers of the retina, ultimately leading to significant and direct intracellular delivery; this being effectively demonstrated across three relevant and distinct retinal cell lines. Stably engineered nanobubbles of a highly homogenous and echogenic nature were fully characterised using dynamic light scattering, B-scan ultrasound and transmission electron microscopy (TEM). The nanobubbles appeared as spherical liposome-like structures under TEM, accompanied by an opaque luminal core and darkened corona around their periphery, with both features indicative of efficient gas entrapment and adsorption, respectively. A nanobubble +/- ultrasound sweeping study was conducted next, which determined the maximum tolerated dose for each cell line. Detection of underlying cellular stress was verified using the biomarker heat shock protein 70, measured before and after treatment with optimised ultrasound. Next, with safety to nanobubbles and optimised ultrasound demonstrated, each human or mouse-derived cell population was incubated with biotinylated rabbit-IgG in the presence and absence of ultrasound +/- nanobubbles. Intracellular delivery of antibody in each cell type was then quantified using Cy3-streptavidin. Nanobubbles and optimised ultrasound were found to be negligibly toxic across all cell lines tested. Macromolecular internalisation was achieved to significant, yet varying degrees in all three cell lines. The results of this study pave the way towards better understanding mechanisms underlying cellular responsiveness to ultrasound-triggered drug delivery in future ex vivo and in vivo models of the posterior eye.

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Section: Discussionmentioning

confidence: 99%

Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina

et al. 2017

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“…“Cavitation” is defined as the formation and activity of gas bubbles (Leighton 1994; Paliwal et al 2006; Saroha et al 2011). Cavitation has been shown to enable the penetration of drugs and macromolecules to the cell (Guzman et al 2002; Lawrie et al 1999; Liu et al 1998; Paliwal et al 2006). In the case of stable cavitation, the sheer stresses and micro-streaming around bubbles that are oscillating in the ultrasound field can cause the rupture in the cell membrane (Miller 1987).…”

Section: Discussionmentioning

confidence: 99%

Ultrasound-Enhanced Delivery of Antibiotics and Anti-Inflammatory Drugs Into the Eye

Nabili

Patel

Mahesh

et al. 2013

Ultrasound in Medicine & Biology

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Delivery of sufficient amounts of therapeutic drugs into the eye is often a challenging task. In this study, ultrasound application (frequencies of 400 KHz to 1 MHz, intensities of 0.3–1.0 W/cm2 and exposure duration of 5 min) was investigated to overcome the barrier properties of cornea, which is a typical route for topical administration of ophthalmic drugs. Permeability of ophthalmic drugs, tobramycin and dexamethasone and sodium fluorescein, a drug-mimicking compound, was studied in ultrasound- and sham-treated rabbit corneas in vitro using a standard diffusion cell setup. Light microscopy observations were used to determine ultrasound-induced structural changes in the cornea. For tobramycin, an increase in permeability for ultrasound- and sham-treated corneas was not statistically significant. Increase of 46%–126% and 32%–109% in corneal permeability was observed for sodium fluorescein and dexamethasone, respectively, with statistical significance (p < 0.05) achieved at all treatment parameter combinations (compared with sham treatments) except for 1-MHz ultrasound applications for dexamethasone experiments. This permeability increase was highest at 400 kHz and appeared to be higher at higher intensities applied. Histologic analysis showed structural changes that were limited to epithelial layers of cornea. In summary, ultrasound application provided enhancement of drug delivery, increasing the permeability of the cornea for the anti-inflammatory ocular drug dexamethasone. Future investigations are needed to determine the effectiveness and safety of this application in in vivo long-term survival studies. (E-mail: mnabili@gwu.edu)

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“…Calorimetry was used because this specific method is commonly used in the literature to estimate ultrasonic power (31). The three powers at 20 kHz were 2.5, 5, and 7.5 W/cm 2 .…”

Section: Methodsmentioning

confidence: 99%

Ultrasound-mediated gastrointestinal drug delivery

et al. 2015

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There is a significant clinical need for rapid and efficient delivery of drugs directly to the site of diseased tissues for the treatment of gastrointestinal (GI) pathologies, in particular, Crohn’s and ulcerative colitis. However, complex therapeutic molecules cannot easily be delivered through the GI tract because of physiologic and structural barriers. We report the use of ultrasound as a modality for enhanced drug delivery to the GI tract, with an emphasis on rectal delivery. Ultrasound increased the absorption of model therapeutics inulin, hydrocortisone, and mesalamine two- to tenfold in ex vivo tissue, depending on location in the GI tract. In pigs, ultrasound induced transient cavitation with negligible heating, leading to an order of magnitude enhancement in the delivery of mesalamine, as well as successful systemic delivery of a macromolecule, insulin, with the expected hypoglycemic response. In a rodent model of chemically induced acute colitis, the addition of ultrasound to a daily mesalamine enema (compared to enema alone) resulted in superior clinical and histological scores of disease activity. In both animal models, ultrasound treatment was well tolerated and resulted in minimal tissue disruption, and in mice, there was no significant effect on histology, fecal score, or tissue inflammatory cytokine levels. The use of ultrasound to enhance GI drug delivery is safe in animals and could augment the efficacy of GI therapies and broaden the scope of agents that could be delivered locally and systemically through the GI tract for chronic conditions such as inflammatory bowel disease.

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Cited by 132 publications

References 18 publications

Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina

Stably engineered nanobubbles and ultrasound - An effective platform for enhanced macromolecular delivery to representative cells of the retina

Ultrasound-Enhanced Delivery of Antibiotics and Anti-Inflammatory Drugs Into the Eye

Ultrasound-mediated gastrointestinal drug delivery

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