title: Ultrasound-mediated transscleral delivery of macromolecules to the posterior segment of rabbit eye in vivo.
abstract: OBJECTIVE
  This study aims to determine the in vivo effectiveness of low-frequency ultrasound in mediating the transport of macromolecules to the posterior segment of the eye via transscleral route. It investigates if damage is caused by ultrasound at the tested operation parameters on the posterior ocular tissues and visual function.
  
  
  METHODS
  Ultrasound (I(SATA) = 0.12 W/cm(2), center frequency = 40 kHz, 90-second continuous wave) was applied on the sclera of New Zealand white rabbits for one to three cycles. Solution of fluorescent dextran (70 kDa) was placed above sclera during and after ultrasound application to assess transscleral transport of macromolecules. Amount of dextran delivered to vitreous was determined by detection of fluorescence. Visual function of ultrasound-treated rabbits was examined by full-field electroretinography (ffERG). The effect of ultrasound on ocular tissue structures was examined by binocular indirect ophthalmoscope (BIO) and histology.
  
  
  RESULTS
  Repeated ultrasound resulted in increasing concentration of dextran, which was otherwise undetectable in the vitreous. Transscleral barrier against dextran transport was restored to original value at 2 weeks postultrasound treatment. Studies from ffERG suggested that electric responses from neural transmission of retinal cells are normal at 1 day, 7 days, and 14 days after ultrasound applications. BIO and histology revealed no structural abnormality in posterior ocular tissues after ultrasound treatment.
  
  
  CONCLUSIONS
  Low-frequency ultrasound significantly enhanced the penetration of macromolecules via transscleral route. No undesirable side effects have been found for up to 2 weeks after ultrasound application. The study supports that sonication is a potentially safe and effective method to modulate transscleral barriers for delivering macromolecular therapeutics to posterior segment of the eye.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Wai-Leung Langston
authors.initials: WL
authors.lastname: Suen
authors.forename: Hoi Sang
authors.initials: HS
authors.lastname: Wong
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.forename: Laurence Chi Ming
authors.initials: LC
authors.lastname: Lau
authors.forename: Amy Cheuk-Yin
authors.initials: AC
authors.lastname: Lo
authors.forename: Ying
authors.initials: Y
authors.lastname: Chau
mesh_terms: D000818:Animals; D003911:Dextrans / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000379:methods*; D004596:Electroretinography; D005453:Fluorescence; D007478:Iontophoresis / Q000379:methods; D046911:Macromolecular Substances / Q000493:pharmacokinetics*; D009887:Ophthalmoscopy; D057972:Posterior Eye Segment / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D012164:Retinal Diseases / Q000188:drug therapy; D012590:Sclera / Q000378:metabolism*; D014465:Ultrasonics / Q000379:methods*; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D003911:Dextrans; D046911:Macromolecular Substances
keywords: needleless; noninvasive; ocular delivery; retinal disease