Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound (HIFU): An<i>Ex Vivo</i>Study

Murugappan, Suresh Kanna; Zhou, Yufeng

doi:10.3109/02713683.2014.980006

Cited by 11 publications

(27 citation statements)

References 29 publications

(29 reference statements)

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“…It is therefore difficult to draw conclusions on which US parameter set should be used for a particular application. The used frequency varies from 20 [71]. Considering these important differences between the exposure conditions, it is difficult to draw conclusions on ideal US parameters.…”

Section: Efficacymentioning

confidence: 99%

“…Moreover, thermal effects, responsible for deleterious side effects, are not shown to be responsible for drug delivery efficacy. Thus, the most promising strategy is to use pulsed mode ultrasound in order to maintain cavitation without inducing temperature elevation [71,72]. However, although temperature elevations are relatively easy to monitor, cavitation remains harder to quantify.…”

Section: Expert Opinionmentioning

confidence: 99%

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Ultrasound-mediated ocular delivery of therapeutic agents: a review

Lafond

Aptel

Mestas

et al. 2016

Expert Opinion on Drug Delivery

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Introduction: Due to numerous anatomical and physiological barriers, ocular drug delivery remains a major limitation in the treatment of diseases such as glaucoma, macular degeneration or inflammatory diseases. To date, only invasive approaches provide clinically effective results. Ultrasound can be defined as the propagation of a high-frequency sound wave exposing the propagation media to mechanical and thermal effects. Ultrasound has been proposed as a non-invasive physical agent for increasing therapeutic agent delivery in various fields of medicine.Areas Covered: An update on recent advances in transscleral and transcorneal ultrasoundmediated drug delivery is presented. Efficient drug delivery is achieved in vitro, ex vivo and in vivo for various types of materials. Numerous studies indicate that efficacy is related to Downloaded by [University of Lethbridge] at 02:55 18 June 2016 2 cavitation. Although slight reversible effects can be observed on the corneal epithelium, efficient drug delivery can be performed without causing damage to the cornea. Expert Opinion: Recent developments prove the potential of ultrasound-mediated ocular drug delivery. Cavitation appears to be a preponderant mechanism, opening a way to treatment monitoring by cavitation measurement. Even if no clinical studies have yet been performed, the promising results summarized here are promoting developments toward clinical applications, particularly in assessing the safety of the technique. Article highlights box• Ocular drug delivery limits the treatment of numerous diseases because of anatomical and physiological barriers so that current techniques are either inefficient (5% of the dose reaching the interior of the eye) or invasive (intravitreal injections, implants).• Ultrasound offers the possibility of acting noninvasively on the sclera or cornea.• Both in vitro and in vivo experiments report an increase in transscleral and transcorneal drug delivery by applying ultrasound which could suggest an increased treatment efficacy.• The mechanism of enhanced drug delivery is attributable to cavitation, producing slight, reversible changes in tissues.• Slight reversible damages attributable could be found. Thus, with an efficient cavitation monitoring procedure, translation to the clinic should be encouraged, as no severe damage has been observed. Downloaded by [University of Lethbridge] at 02:55 18 June 2016 3• The strategy of dosing the ultrasound exposure on measured cavitation activity in relation with its calibrated bioeffects in terms of damages and efficacy is proposed.Also, future developments shall benefit from the experience of sonophoresis.

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Section: Efficacymentioning

confidence: 99%

Section: Expert Opinionmentioning

confidence: 99%

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Lafond

Aptel

Mestas

et al. 2016

Expert Opinion on Drug Delivery

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“…24 Ocular ointments are the easiest method of drug delivery but do not stay on the eye long enough. 25 Therefore, drug absorption is limited to a few minutes and the bioavailability is low. 25 High-intensity focused ultrasound-mediated drug delivery could be a potential treatment option for ocular disorders.…”

Section: Applicationsmentioning

confidence: 99%

Using High-Intensity Focused Ultrasound as a Means to Provide Targeted Drug Delivery

McClure

2016

Journal of Diagnostic Medical Sonography

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Cancer is a prevalent condition affecting millions of individuals worldwide. According to the United Kingdom's Cancer Research Center, 1 there are more than 200 different forms of cancer. Many patients living with cancer are not eligible for certain forms of treatment due to tumor size, location, and multi-focality or multi-centricity. 2 A highintensity focused ultrasound (HIFU)-mediated drug delivery system, or sonophoresis, has the capability to provide patients with a potential alternative. 3 This novel approach provides patients with a targeted noninvasive treatment option for a variety of different cancers as well as other disorders. 3 Sonophoresis is a process that can accelerate the absorption of a localized treatment compared to other types of cancer treatments that are more invasive or damaging to the patient. 3 This technique is considered a form of HIFU. Cancer is a devastating disease that can oftentimes ravish the body. Management of cancer often involves harsh treatment options over the course of several months or years. A clear issue with cancer treatment is the use of aggressive chemicals and radiation. One of the shortcomings is the lack of targeting, which results in several undesirable side effects for many patients. Those who receive chemotherapy can sometimes find it difficult to attend work and live normally. According to the World Health Organization 4 (WHO), cancer rates are on a steep incline, and it is predicted that approximately 15 million new cases of cancer will be reported by the year 2020. The average of all cancer survival rates is approximately 50%; therefore, finding different treatment options is crucial. 5 The most popular forms of treatment for cancer are chemotherapy, radiation, and surgery. These treatment options prove to be painful and uncomfortable for the patient for long durations. Some forms of treatment are limited because of tumor specifics. 2 Efforts are being made to reduce doselimiting toxicity and improve localized drug delivery. High-intensity focused ultrasound-mediated drug delivery could provide a noninvasive and safe approach to treating a variety of cancers within the body.

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“…Pulsed high-intensity focused ultrasound has been also studied recently in order to facilitate drug delivery across the sclera noninvasively. 103 …”

Section: Advances In Drug Delivery To the Posterior Segmentmentioning

confidence: 99%

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

Agarwal¹,

Rhoades²,

Hanout³

et al. 2015

OPTH

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Contemporary management of neovascular age-related macular degeneration (AMD) has evolved significantly over the last few years. The goal of treatment is shifting from merely salvaging vision to maintaining a high quality of life. There have been significant breakthroughs in the identification of viable drug targets and gene therapies. Imaging tools with near-histological precision have enhanced our knowledge about pathophysiological mechanisms that play a role in vision loss due to AMD. Visual, social, and vocational rehabilitation are all important treatment goals. In this review, evidence from landmark clinical trials is summarized to elucidate the optimum modern-day management of neovascular AMD. Therapeutic strategies currently under development, such as gene therapy and personalized medicine, are also described.

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Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound (HIFU): AnEx VivoStudy

Abstract: In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth. In vivo studies are necessary to further evaluate its performance, including the drug penetration and its possible side effects.

Cited by 11 publications

References 29 publications

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Using High-Intensity Focused Ultrasound as a Means to Provide Targeted Drug Delivery

Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development

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Transsclera Drug Delivery by Pulsed High-Intensity Focused Ultrasound (HIFU): AnEx VivoStudy

Abstract: In summary, pulsed-HIFU may be an effective modality in the transsclera drug delivery with a high transporting rate and depth. In vivo studies are necessary to further evaluate its performance, including the drug penetration and its possible side effects.

Cited by 11 publications

References 29 publications

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Using High-Intensity Focused Ultrasound as a Means to Provide Targeted Drug Delivery

Management of neovascular age-related macular degeneration: current state-of-the-art care for&nbsp;optimizing visual outcomes and therapies in&nbsp;development

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Management of neovascular age-related macular degeneration: current state-of-the-art care for optimizing visual outcomes and therapies in development