title: Ultrasound-enhanced intrascleral delivery of protein.
abstract: We aim to investigate ultrasound on enhancing protein penetration into the sclera, a non-invasive method to overcome the first barrier in taking the transscleral route for delivering therapeutics. Rabbit eyes were immersed in a fluorescein isothiocyanate conjugated bovine serum albumin solution. The distances of protein penetration, with and without ultrasound (30s continuous wave, 1MHz, 0.05W/cm(2)) applied on the sclera, and at different immersion time intervals (0, 5, 15, 30 and 60min), were measured by examining the cryo-sectioned tissues under fluorescence microscope (≥60 measurements from 3 eyes for each condition). Retina was examined for structural damage by histology. It was found that ultrasound enhances the intrascleral penetration of protein, increasing the diffusivity by 1.6-folds while causing no damage to the retinal tissues. This physical modulation of the sclera is temporary, as evident by the restoration of the diffusional resistance at 15min after ultrasound treatment. The negligible effect of ultrasound-induced convection and the minimal temperature rise (<0.5°C), together with cavitation detected by acoustic emission and a decreased penetration distance at higher ultrasound frequency (30s continuous wave, 3MHz, 0.05W/cm(2)), suggest that cavitation is a possible mechanism for increasing the permeability of the sclera for diffusive transport.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Alex Chi Yeung
authors.initials: AC
authors.lastname: Cheung
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Tay
authors.forename: Hoi Sang
authors.initials: HS
authors.lastname: Wong
authors.forename: Rutledge
authors.initials: R
authors.lastname: Ellis-Behnke
authors.forename: Ying
authors.initials: Y
authors.lastname: Chau
mesh_terms: D000818:Animals; D001692:Biological Transport; D002417:Cattle; D004058:Diffusion; D016503:Drug Delivery Systems; D008856:Microscopy, Fluorescence; D010539:Permeability; D015612:Phonophoresis; D011506:Proteins / Q000008:administration & dosage / Q000378:metabolism*; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism*; D012709:Serum Albumin / Q000008:administration & dosage / Q000378:metabolism; D013696:Temperature
chemical_list: D011506:Proteins; D012709:Serum Albumin