Ultrasound-Mediated Transscleral Delivery of Macromolecules to the Posterior Segment of Rabbit Eye In Vivo

Suen, Wai-Leung; Wong, Hoi Sang; Yu, Yu; Lau, Chi Ming Laurence; Lo, Amy Cheuk Yin; Chau, Ying

doi:10.1167/iovs.13-11978

Cited by 38 publications

(45 citation statements)

References 41 publications

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“…Most of the experiments were performed either in vitro on isolated cornea or sclera or ex vivo on entire excised eyes until 2006 [6]. Between 2006 and 2013, the majority of the studies were conducted in vivo [6,7,[66][67][68]. In the last in vivo study to date which has been found, dexamethasone (a steroidal anti-inflammatory agent) has been delivered to the aqueous humor at 2.8 times the passive penetration using 5-minute continuous wave ultrasound (CWUS) with moderate intensities (0.8W/cm²) at 400kHz [69].…”

Section: Efficacymentioning

confidence: 99%

“…In the last in vivo study to date which has been found, dexamethasone (a steroidal anti-inflammatory agent) has been delivered to the aqueous humor at 2.8 times the passive penetration using 5-minute continuous wave ultrasound (CWUS) with moderate intensities (0.8W/cm²) at 400kHz [69]. In an earlier study, transscleral delivery of fluorescein-labelled dextran has been achieved using low-frequency US (40kHz) [68]. In this particular study, significant amounts of dextran were measured in the vitreous humor (up to 1.48 µg/g), while it was undetectable without applying ultrasound.…”

Section: Efficacymentioning

confidence: 99%

“…For these reasons, most of the studies about US-mediated ocular drug delivery investigate the potential damages on tissues du to US exposures (summarized in Table 1). Safety-oriented studies have failed to find any evidence of severe eye tissue damage [4,6,7,9,68 The thermal safety of ultrasound-enhanced ocular delivery has been evaluated numerically [78]. Ultrasound exposure conditions of 5 minutes at 400 kHz -1MHz and intensities of 0.3 -1 W/cm² were considered.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…Also, the lack of long term follow-up could constitute another challenge for clinical use, the longest one being 14 days [68]. Long-term efficacy and tolerability have to be evaluated.…”

Section: Perspectivesmentioning

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: Efficacymentioning

confidence: 99%

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…Also, the lack of long term follow-up could constitute another challenge for clinical use, the longest one being 14 days [68]. Long-term efficacy and tolerability have to be evaluated.…”

Section: Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Lafond

Aptel

Mestas

et al. 2016

Expert Opinion on Drug Delivery

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show abstract

“…Drug delivery using sonophoresis (or ultrasound) to increase ocular tissue permeability is earlier in development and has not yet been demonstrated in clinical studies. Delivery of steroids, antibiotics, and, most recently, a large molecular weight dextran has been demonstrated in preclinical models, however [157, 160, 161]. …”

Section: Ophthalmic Drug Deliverymentioning

confidence: 99%

Single compartment drug delivery

Cima

Lee²,

Daniel³

et al. 2014

Journal of Controlled Release

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Drug design is built on the concept that key molecular targets of disease are isolated in the diseased tissue. Systemic drug administration would be sufficient for targeting in such a case. It is, however, common for enzymes or receptors that are integral to disease to be structurally similar or identical to those that play important biological roles in normal tissues of the body. Additionally, systemic administration may not lead to local drug concentrations high enough to yield disease modification because of rapid systemic metabolism or lack of sufficient partitioning into the diseased tissue compartment. This review focuses on drug delivery methods that physically target drugs to individual compartments of the body. Compartments such as the bladder, peritoneum, brain, eye and skin are often sites of disease and can sometimes be viewed as “privileged,” since they intrinsically hinder partitioning of systemically administered agents. These compartments have become the focus of a wide array of procedures and devices for direct administration of drugs. We discuss the rationale behind single compartment drug delivery for each of these compartments, and give an overview of examples at different development stages, from the lab bench to phase III clinical trials to clinical practice. We approach single compartment drug delivery from both a translational and a technological perspective.

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Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management

Zhou,

Xu,

Shen

et al. 2024

Adv Healthcare Materials

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As an indispensable part of the human sensory system, visual acuity may be impaired and even develop into irreversible blindness due to various ocular pathologies. Among ocular diseases, fundus neovascularization diseases (FNDs) are prominent etiologies of visual impairment worldwide. Intravitreal injection of anti‐vascular endothelial growth factor drugs remains the primary therapy but is hurdled by common complications and incomplete potency. To renovate the current therapeutic modalities, nanomedicine emerged as the times required, which has been endowed with advanced capabilities, able to fulfill the effective ocular fundus drug delivery and achieve precise drug release control, thus further improving the therapeutic effect. This review provides a comprehensive summary of advances in nanomedicine for FND management from state‐of‐the‐art studies. Firstly, we thoroughly introduce the current therapeutic modalities for FNDs, focusing on the key challenges of ocular fundus drug delivery. Secondly, we comprehensively reviewed nanocarriers for ocular posterior drug delivery based on the nanostructures: polymer‐based nanocarriers, lipid‐based nanocarriers, and inorganic nanoparticles. Thirdly, we elaborate on the characteristics of the fundus microenvironment, their pathological changes during FNDs, and corresponding strategies for constructing smart nanocarriers. Furthermore, the challenges and prospects of nanomedicine for FND management are thoroughly discussed.This article is protected by copyright. All rights reserved

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Ultrasound-Mediated Transscleral Delivery of Macromolecules to the Posterior Segment of Rabbit Eye In Vivo

Cited by 38 publications

References 41 publications

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Single compartment drug delivery

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management

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