title: Examination of Effects of Low-Frequency Ultrasound on Scleral Permeability and Collagen Network.
abstract: Delivery of therapeutics to the intraocular space or to targeted tissues in the posterior segment is challenging because of the structural and dynamic barriers surrounding the eye. Previously, we reported the feasibility of using ultrasound (US) irradiation to deliver macromolecules to the posterior segment of the eye via the transscleral route, which consists of sclera as the outermost anatomic barrier. In this study, we found that although ultrasound increases scleral permeability for macromolecules, the scleral collagen arrangement remains undisturbed. In an ex vivo experiment, protein permeation across the sclera was significantly enhanced by ultrasound in the stable cavitation regime. The scleral collagen network was further examined by second harmonic generation imaging. Quantitative image analysis techniques were adopted to examine the density, anisotropy and interlacing pattern of collagen fibers before and after ultrasound irradiation. Repeated ultrasound applications did not induce significant changes in the arrangement of collagen fibrils at 40 kHz with a spatial average temporal average intensity (ISATA) <1.8 W/cm2. These parameters correspond to a mechanical index (MI) below 0.8 in our setting. These data suggested that enhanced permeation of macromolecules across the sclera was achieved without disturbing the collagen network of the sclera. This evidence supports that low-frequency, low-intensity ultrasound is a tolerable approach to transscleral drug delivery.
authors: Department of Chemical and Biomolecular Engineering, Hong Kong University of Science and Technology, Hong Kong, China.
authors: Wai-Leung Langston
authors: WL
authors: Suen
authors: Department of Electronic and Computer Engineering, Hong Kong University of Science and Technology, Hong Kong, China.
authors: Jun
authors: J
authors: Jiang
authors: Department of Chemical and Biomolecular Engineering, Hong Kong University of Science and Technology, Hong Kong, China.
authors: Hoi Sang
authors: HS
authors: Wong
authors: Department of Electronic and Computer Engineering, Hong Kong University of Science and Technology, Hong Kong, China.
authors: Jianan
authors: J
authors: Qu
authors: Department of Chemical and Biomolecular Engineering, Hong Kong University of Science and Technology, Hong Kong, China; Division of Biomedical Engineering, Hong Kong University of Science and Technology, Hong Kong, China. Electronic address: ying.chau@ust.hk.
authors: Ying
authors: Y
authors: Chau
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D046911:Macromolecular Substances / Q000378:metabolism*; D023421:Models, Animal; D010539:Permeability; D011817:Rabbits; D012590:Sclera / Q000000981:diagnostic imaging*; D000069453:Ultrasonic Waves; D014463:Ultrasonography / Q000379:methods*
chemical_list: D046911:Macromolecular Substances; D003094:Collagen
keywords: Collagen; Drug delivery; Mechanical index; Scleral permeability; Second harmonic generation imaging; Texture analysis