title: Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery.
abstract: In ocular drug delivery, the sclera is a promising pathway for administering drugs to both the anterior and posterior segments of the eye. Due to the low permeability of the sclera, however, efficient drug delivery is challenging. In this study, pulsed ultrasound (US) was investigated as a potential method for enhancing drug delivery to the eye through the sclera. The permeability of rabbit scleral tissue to a model drug compound, sodium fluorescein, was measured after US-irradiation at 1.1 MHz using time-averaged acoustic powers of 0.5-5.4 W (6.8-12.8 MPa peak negative pressure), with a fixed duty cycle of 2.5% for two different pulse repetition frequencies of 100 and 1000 Hz. Acoustic cavitation activity was measured during exposures using a passive cavitation detector and was used to quantify the level of bubble activity. A correlation between the amount of cavitation activity and the enhancement of scleral permeability was demonstrated with a significant enhancement in permeability of US exposed samples compared to controls. Transmission electron microscopy showed no evidence of significant alteration in viability of tissue exposed to US exposures. A pulsed US protocol designed to maximum cavitation activity may therefore be a viable method for enhancing drug delivery to the eye.
authors.affiliation: Inserm, Unité 1032, Lab TAU, Lyon, France; EyeTechCare, Rillieux la Pape, France. Electronic address: arash.razavi@inserm.fr.
authors.forename: Arash
authors.initials: A
authors.lastname: Razavi
authors.affiliation: EyeTechCare, Rillieux la Pape, France.
authors.forename: David
authors.initials: D
authors.lastname: Clement
authors.affiliation: Inserm, Unité 1032, Lab TAU, Lyon, France.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Fowler
authors.affiliation: Inserm, Unité 1032, Lab TAU, Lyon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Birer
authors.affiliation: Inserm, Unité 1032, Lab TAU, Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Chavrier
authors.affiliation: Inserm, Unité 1032, Lab TAU, Lyon, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mestas
authors.affiliation: EyeTechCare, Rillieux la Pape, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Romano
authors.affiliation: Inserm, Unité 1032, Lab TAU, Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Chapelon
authors.affiliation: EyeTechCare, Rillieux la Pape, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Béglé
authors.affiliation: Inserm, Unité 1032, Lab TAU, Lyon, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Lafon
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D019793:Fluorescein / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D011817:Rabbits; D012590:Sclera; D013010:Sonication / Q000379:methods*
chemical_list: D019793:Fluorescein
keywords: Cavitation; Ocular drug delivery; Sclera; Therapeutic ultrasound; Transsclera