Contribution of Inertial Cavitation in the Enhancement of In Vitro Transscleral Drug Delivery

Razavi, Arash; Clément, David; Fowler, Robert; Birer, Alain; Chavrier, F.; Mestas, Jean‐Louis; Romano, Fabrice; Chapelon, Jean‐Yves; Béglé, Aurélie; Lafon, Cyril

doi:10.1016/j.ultrasmedbio.2013.12.032

Cited by 16 publications

(31 citation statements)

References 55 publications

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“…MPa [72]. In this last study, a correlation between an inertial cavitation index and drug delivery efficiency has been demonstrated.…”

Section: Efficacymentioning

confidence: 64%

“…These changes are likely related to cavitation [70,72] and could potentially explain the enhancement of drug delivery. Indeed, the corneal epithelium is the first strong lipophilic barrier of the cornea, and most of the drugs or molecules used were hydrophilic.…”

Section: Safety and Tolerabilitymentioning

confidence: 99%

“…Regarding the sclera, some of the studies have demonstrated histological changes due to ultrasound exposition [72]. As the sclera is not a transparent layer and is much less innervated than the cornea, these histological changes are also probably acceptable.…”

Section: Safety and Tolerabilitymentioning

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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“…MPa [72]. In this last study, a correlation between an inertial cavitation index and drug delivery efficiency has been demonstrated.…”

Section: Efficacymentioning

confidence: 64%

Section: Safety and Tolerabilitymentioning

confidence: 99%

Section: Safety and Tolerabilitymentioning

confidence: 99%

Section: Expert Opinionmentioning

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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“…Another recent study by Razavi et al showed that ultrasound can enhance the delivery of fluorescein sodium via the scleral route with no significant alteration observed in the eye tissues. 17 In this study, inertial cavitation was shown to be the mechanism responsible for this delivery enhancement.…”

Section: Introductionmentioning

confidence: 75%

Thermal safety of ultrasound‐enhanced ocular drug delivery: A modeling study

2015

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The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm(2) (parameters shown in the authors' previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this method in the whole orbit especially regarding potential adverse optic nerve heating at the location of the bone.

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