Ultrasound-enhanced intrascleral delivery of protein

Cheung, Alex; Yu, Yu; Tay, David; Wong, Hoi Sang; Ellis-Behnke, Rutledge; Chau, Ying

doi:10.1016/j.ijpharm.2010.09.001

Cited by 38 publications

(59 citation statements)

References 36 publications

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“…While the majority of studies were once based on CWUS, findings on the mechanistic effects of US-mediated ocular drug delivery reoriented treatment strategy. Indeed, a large number of studies have associated drug delivery efficacy with cavitation [4,6,10,45,70]. This was confirmed with studies using low duty cycles and high pressure amplitudes.…”

Section: Efficacymentioning

confidence: 78%

“…However, in some studies increased permeability only occurs during insonication, and not after, whereas some of the tissue changes are sustained, suggesting that the material has to be in the sonicated zone while applying ultrasound [4,6,7]. Similarly, separate administration of ultrasound first, followed by the drug solution, did not lead every time to an increased permeability.…”

Section: Safety and Tolerabilitymentioning

confidence: 97%

“…Despite the fact that experimental studies seem to confirm the potential efficacy of ultrasound ocular drug delivery, safety has yet to be demonstrated, particularly regarding the cornea, which is a transparent structure, and clinical evidence is still lacking [4][5][6][7][8][9][10]. Scleral ultrasound drug delivery may be Downloaded by [University of Lethbridge] at 02: 55 18 June 2016 complementary to corneal drug delivery, as it can address a wider range of ocular diseases, including diseases of the posterior segment of the eye.…”

Section: General Contextmentioning

confidence: 99%

“…These studies showed encouraging results. Cheung et al, for example, showed that low-power ultrasound (0.05 W/cm2 at 3 MHz in continuous wave) could enhance the penetration depth of fluorescein in an isolated rabbit sclera by 50% [4]. On an ex vivo rabbit cornea, permeability can be increased by 2.1-4.2 times with continuous 880 kHz ultrasound for intensities of respectively 0.19 and 0.56 W/cm 2 [10].…”

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%

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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: 78%

Section: Safety and Tolerabilitymentioning

confidence: 97%

Section: General Contextmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

Section: Safety and Tolerabilitymentioning

confidence: 99%

See 3 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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Low‐intensity low‐frequency ultrasound mediates riboflavin delivery during corneal crosslinking

Sun

Chung

et al. 2022

Bioengineering & Transla Med

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We employed the mechanical effect from 40 kHz ultrasound (US) to improve the delivery of riboflavin into corneal stroma for collagen crosslinking, which can benefit the treatment of keratoconus and other corneal ectasias. Experiments were conducted, first with porcine corneas ex vivo and then with New Zealand white rabbits in vivo, at varying mechanical index (MI) and sonication time. Results showed that 15 min of US applied on the cornea at MI = 0.8 in the presence of 0.5% of riboflavin solution enabled its delivery to deeper corneal stroma. Excessive heat was removed by a cooling setup to negate the thermal effect. The corneal absorption amount and penetration of riboflavin through cornea as detected by fluorotron, as well as the enhancement of corneal stiffness as measured by Young's modulus, were comparable to the conventional approach that requires complete corneal epithelium debridement. Histological analysis revealed minor exfoliation of superficial cell layers of corneal epithelium and loss of ZO‐1 tight junctions immediately after US. Full recovery of the corneal epithelium and restoration of tight junctions occurred in 3–4 days. The study shows that low‐intensity low‐frequency ultrasound (LILF US) is a less invasive alternative to the conventional epithelium‐off method for delivering riboflavin into the corneal stroma.

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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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Ultrasound-enhanced intrascleral delivery of protein

Cited by 38 publications

References 36 publications

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Ultrasound-mediated ocular delivery of therapeutic agents: a review

Low‐intensity low‐frequency ultrasound mediates riboflavin delivery during corneal crosslinking

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

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