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

Yang, Chen-Yen; Jessen, Jordan; Lin, Ken

doi:10.1002/jcu.23214

Cited by 8 publications

(6 citation statements)

References 132 publications

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“…Although there is growing interest in utilizing drug-filled microbubbles with insonation as a mechanism for targeted drug delivery, there remains a need to characterize the relationship between ultrasound and microbubble cargo in the absence of microbubbles [21]. Our study reveals ultrasound variably influences the potency of cisplatin and doxorubicin-HCl in vitro.…”

Section: Discussionmentioning

confidence: 81%

Pulsed Ultrasound Modulates the Cytotoxic Effect of Cisplatin and Doxorubicin on Cultured Human Retinal Pigment Epithelium Cells (ARPE-19)

Mohammadi,

LaRocca,

Yang

et al. 2023

JCTO

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Objective: Pulsed ultrasound has been proposed as a tool to enhance ocular drug delivery, but its effects on drug potency are not well understood. Doxorubicin-HCl and cisplatin are two drugs commonly used to treat ocular melanoma. We report the effects of pulsed ultrasound on the cytotoxicity of doxorubicin-HCl and cisplatin in vitro. Methods: Cultured human retinal pigment epithelium cells (ARPE-19) were treated with doxorubicin-HCl or cisplatin in the presence or absence of ultrasound. MTT and Trypan blue assays were performed at 24 and 48 h post treatment to assess cell metabolism and death. Results: Cells treated with ultrasound plus doxorubicin-HCl demonstrated a significant decrease in metabolism compared with cells treated with doxorubicin-HCl alone. In contrast, cells treated with ultrasound plus cisplatin exhibited a significant increase in metabolism compared with cells treated with cisplatin alone for 48 h. Cells treated with cisplatin and pretreated with ultrasound (US–Cis) exhibited a significant decrease in metabolism. Cell death was similar in doxorubicin- and cisplatin-treated cells with and without ultrasound. Conclusion: Pulsed ultrasound enhances the cytotoxicity of doxorubicin-HCl at 24 and 48 h post treatment but abrogates cisplatin toxicity 48 h post treatment. This suggests ultrasound modulates cell–drug interactions in a drug-specific manner. These findings may influence the future development of ultrasound-assisted ocular drug delivery systems.

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Section: Discussionmentioning

confidence: 81%

Pulsed Ultrasound Modulates the Cytotoxic Effect of Cisplatin and Doxorubicin on Cultured Human Retinal Pigment Epithelium Cells (ARPE-19)

Mohammadi,

LaRocca,

Yang

et al. 2023

JCTO

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“…Although there is growing interest in utilizing drug-filled microbubbles with insonation as a mechanism for targeted drug delivery, there remains a need to characterize the relationship between ultrasound and microbubble cargo in the absence of microbubbles [20]. Our study reveals ultrasound variably influences the potency of cisplatin and doxorubicin-HCl in vitro .…”

Section: Discussionmentioning

confidence: 87%

Pulsed ultrasound modulates the cytotoxic effect of cisplatin and doxorubicin on cultured human retinal pigment epithelium cells (ARPE-19)

Mohammadi,

LaRocca,

Yang

et al. 2023

Preprint

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ObjectivePulsed ultrasound has been proposed as a tool to enhance ocular drug delivery, but its effects on drug potency are not well understood. Doxorubicin-HCl and cisplatin are two drugs commonly used to treat ocular melanoma. We report the effects of pulsed ultrasound on the cytotoxicity of doxorubicin-HCl and cisplatinin vitro.MethodsCultured human retinal pigment epithelium cells (ARPE-19) cells were treated with doxorubicin-HCl or cisplatin in the presence or absence of ultrasound. MTT and Trypan blue assays were performed at 24 and 48 hours post-treatment to assess cell metabolism and death.ResultsCells treated with ultrasound plus doxorubicin-HCl demonstrated a significant decrease in metabolism compared to cells treated with doxorubicin-HCl alone. In contrast, cells treated with ultrasound plus cisplatin exhibited a significant increase in metabolism compared to cells treated with cisplatin alone at 48-hours. Cells treated with cisplatin pre-treated with ultrasound (US-Cis) exhibited a significant decrease in metabolism. Cell death was similar in doxorubicin- and cisplatin-treated cells with and without ultrasound.ConclusionPulsed ultrasound enhances the cytotoxicity of doxorubicin-HCl at 24- and 48-hours post-treatment but abrogates cisplatin toxicity 48-hours post-treatment. This suggests ultrasound modulates cell-drug interactions in a drug-specific manner. These findings may influence the future development of ultrasound-assisted ocular drug delivery systems.

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“…Latter reviews focused on either ultrasound-mediated ocular delivery of specific agents, including gene delivery [13], or investigated specific drug delivery methods for which ultrasound is used, such as trans-topical delivery [12], and trans-BRB delivery [14]. Most recently, Yang et al (2022) published a review characterising some of the therapeutic benefits and safety concerns of different methods of ultrasound-mediated drug delivery [18].…”

Section: Rationale: Current Therapeutic and Financial Challenges In T...mentioning

confidence: 99%

“…Most recently, Yang et al . (2022) published a review characterising some of the therapeutic benefits and safety concerns of different methods of ultrasound-mediated drug delivery 18 . These reviews highlight both the potential for ultrasound-mediated drug delivery to improve therapeutics and the need for additional safety and tolerability data supporting translation to the clinic.…”

Section: Introductionmentioning

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

Cited by 8 publications

References 132 publications

Pulsed Ultrasound Modulates the Cytotoxic Effect of Cisplatin and Doxorubicin on Cultured Human Retinal Pigment Epithelium Cells (ARPE-19)

Pulsed Ultrasound Modulates the Cytotoxic Effect of Cisplatin and Doxorubicin on Cultured Human Retinal Pigment Epithelium Cells (ARPE-19)

Pulsed ultrasound modulates the cytotoxic effect of cisplatin and doxorubicin on cultured human retinal pigment epithelium cells (ARPE-19)

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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