Examination of Effects of Low-Frequency Ultrasound on Scleral Permeability and Collagen Network

Suen, Wai Leung Langston; Jiang, Jun; Wong, Hoi Sang; Qu, Jianan Y.; Chau, Ying

doi:10.1016/j.ultrasmedbio.2016.07.013

Cited by 9 publications

(19 citation statements)

References 28 publications

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“…The effective thickness of delivery in this study is comparable to the diffusion distance of choromophores into collagen-based structures by ultrasound with/without microbubbles [ 18 , 30 ]. It was reported that 1–2 mm depth of tumor invasion into lamina propria was a negative prognostic factor of non-muscle invasive bladder cancer [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 88%

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model

et al. 2017

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Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.

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Section: Discussionmentioning

confidence: 88%

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model

et al. 2017

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“…A potential concern of scleral ultrasound is that the sclera is a much larger structure than the cornea and that coarse ultrasound application on its surface may lead to morphological or functional injury. However, studies of scleral ultrasound exposure indicate that ultrasound induces no significant changes to the scleral collagen network 100 . These data bolster the idea that ultrasound is a tolerable approach for drug delivery to the posterior segment.…”

Section: Ultrasound As An Ocular Drug Delivery Toolmentioning

confidence: 62%

“…However, studies of scleral ultrasound exposure indicate that ultrasound induces no significant changes to the scleral collagen network. 100 These data bolster the idea that ultrasound is a tolerable approach for drug delivery to the posterior segment.…”

Section: Pre-clinicalmentioning

confidence: 78%

Ultrasound‐assisted ocular drug delivery: A review of current evidence

Yang

Jessen

Lin

2022

J of Clinical Ultrasound

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Efficient ocular drug delivery is a challenging clinical problem with various therapeutic options but no clearly preferred methodology. Given the ubiquity of ultrasound as a diagnostic technique, the safety profile of ultrasound in an ocular context, and the prospect of custom‐made ultrasound‐sensitive contrast agents, ultrasound presents an attractive ocular drug delivery modality. In this review, we evaluate our present understanding of ultrasound as it relates to ocular drug delivery and significant knowledge gaps in the field. In doing so, we hope to call attention to a potentially novel drug delivery pathway that could be manipulated to treat or cure ocular diseases.

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“…Year Animal model Target Coefficient Quality of study reporting [69] 2002 Rabbit Transcorneal to anterior segment 0.36 Insufficient [62] 2004 Rabbit Transcorneal to anterior segment 0.39 Insufficient [60] 2004 Rabbit Transcorneal to anterior segment 0.53 Poor [36] 2006 Rabbit Intrascleral 0.63 Average [37] 2007 Rat Intraconjunctival 0.56 Poor [64] 2008 Bovine Vitreal-retinal uptake 0.42 Poor [82] 2009 Rat Subretinal 0.46 Poor [75] 2009 Rat Vitreal-retinal uptake and blood-retinal barrier 0.39 Insufficient [38] 2009 Rat Vitreal-retinal uptake and subretinal 0.51 Average [77] 2010 Mouse Intravitreal and vitreal-retinal uptake 0.34 Insufficient [76] 2010 Rat Blood-retinal barrier 0.46 Poor [33] 2010 Rat Vitreal-retinal uptake 0.59 Poor [61] 2010 Rabbit Intrascleral 0.53 Poor [28] 2011 Rat Intra-ciliary 0.61 Average [154] 2011 Rat Vitreal-retinal uptake 0.61 Average [66] 2012 Rat Blood-retinal barrier 0.61 Average [65] 2012 Rabbit Vitreal-retinal uptake 0.56 Poor [34] 2012 Rat Vitreal-retinal uptake 0.56 Poor [71] 2013 Rabbit Intrascleral 0.58 Poor [70] 2013 Rabbit Transcorneal to anterior segment 0.44 Poor [39] 2013 Rabbit Transscleral to posterior segment 0.59 Poor [44] 2014 Mice Blood-retinal barrier 0.56 Poor [16] 2014 Rabbit Transcorneal to anterior segment 0.66 Average [74] 2014 Rabbit Transscleral to posterior segment 0.47 Poor [49] 2015 Pig Intrascleral 0.33 Insufficient [83] 2015 Rat Subretinal 0.54 Poor [35] 2016 Rat Subretinal 0.59 Poor [73] 2016 Rabbit Intraconjunctival 0.43 Poor [46] 2016 Rabbit Vitreal-retinal uptake 0.46 Poor [17] 2017 Rat Vitreal-retinal uptake 0.61 Average [72] 2017 Rabbit Intrascleral 0.50 Poor [40] 2017 Pig & Cow Intravitreal and vitreal-retinal uptake 0.56 Poor…”

Section: Refmentioning

confidence: 99%

“…Finally, ultrasound power may also be measured using a hydrophone, whereby the hydrophone is initially positioned at the area of highest pressure from the transducer (ISP), and the plane parallel to the spatial peak position is measured in a 1 cm x 1 cm grid using the "pressure squared interval mode." The data obtained is filtered by omitting values ≤ 0.25 of the peak intensity [113], and the intensity can be calculated by the equation [43,73]:…”

Section: Powermentioning

confidence: 99%

A systematic review of ultrasound-mediated drug delivery to the eye and critical insights to facilitate a timely path to the clinic

Rad,

Chapman,

Tupally

et al. 2023

Theranostics

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Ultrasound has long been identified as a promising, non-invasive modality for improving ocular drug delivery across a range of indications. Yet, with 20 years of learnings behind us, clinical translation remains limited. To help address this, and in accordance with PRISMA guidelines, the various mechanisms of ultrasound-mediated ocular drug delivery have been appraised, ranging from first principles to emergent applications spanning both ex vivo and in vivo models. The heterogeneity of study methods precluded meta-analysis, however an extensive characterisation of the included studies allowed for semi-quantitative and qualitative assessments. Methods: In this review, we reflected on study quality of reporting, and risk of bias (RoB) using the latest Animal Research: Reporting of In Vivo Experiments (ARRIVE 2.0) guidelines, alongside the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) RoB tools. Literature studies from 2002 to 2022 were initially characterised according to methods of ultrasound application, ultrasound parameters applied, animal models employed, as well as safety and efficacy assessments. This exercise contributed to developing a comprehensive understanding of the current state of play within ultrasound-mediated ocular drug delivery. The results were then synthesised and processed into a guide to aid future study design, with the goal of improving the reliability of data, and to support efficient and timely translation to the clinic. Results: Key attributes identified as hindering translation included: poor reporting quality and high RoB, skewed use of animals unrepresentative of the human eye, and the over reliance of reductionist safety assessments. Ex vivo modelling studies were often unable to have comprehensive safety assessments performed on them, which are imperative to determining treatment safety, and represent a pre-requisite for clinical translation. Conclusion:With the use of our synthesised guide, and a thorough understanding of the underlying physicochemical interactions between ultrasound and ocular biology provided herein, this review offers a firm foundation on which future studies should ideally be built, such that ultrasound-mediated ocular drug delivery can be translated from concept to the coalface where it can provide immense clinical benefit.

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Examination of Effects of Low-Frequency Ultrasound on Scleral Permeability and Collagen Network

Cited by 9 publications

References 28 publications

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model

Ultrasound‐assisted ocular drug delivery: A review of current evidence

A systematic review of ultrasound-mediated drug delivery to the eye and critical insights to facilitate a timely path to the clinic

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