title: Intrastromal delivery of bevacizumab using microneedles to treat corneal neovascularization.
abstract: OBJECTIVE
  This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization.
  
  
  METHODS
  Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days.
  
  
  RESULTS
  Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure.
  
  
  CONCLUSIONS
  This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods.
authors.affiliation: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States.
authors.forename: Yoo C
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States.
authors.forename: Henry F
authors.initials: HF
authors.lastname: Edelhauser
authors.affiliation: School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D003319:Corneal Stroma; D004195:Disease Models, Animal; D005260:Female; D007267:Injections / Q000295:instrumentation; D008297:Male; D008904:Miniaturization; D009339:Needles; D010781:Photography; D011817:Rabbits; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: bevacizumab; intrastromal; microneedle; neovascularization