title: Targeted delivery of antiglaucoma drugs to the supraciliary space using microneedles.
abstract: OBJECTIVE
  In this work, we tested the hypothesis that highly targeted delivery of antiglaucoma drugs to the supraciliary space by using a hollow microneedle allows dramatic dose sparing of the drug compared to topical eye drops. The supraciliary space is the most anterior portion of the suprachoroidal space, located below the sclera and above the choroid and ciliary body.
  
  
  METHODS
  A single, hollow 33-gauge microneedle, 700 to 800 μm in length, was inserted into the sclera and used to infuse antiglaucoma drugs into the supraciliary space of New Zealand white rabbits (N = 3-6 per group). Sulprostone, a prostaglandin analog, and brimonidine, an α₂-adrenergic agonist, were delivered via supraciliary and topical administration at various doses. The drugs were delivered unilaterally, and intraocular pressure (IOP) of both eyes was measured by rebound tonometry for 9 hours after injection to assess the pharmacodynamic responses. To assess safety of the supraciliary injection, IOP change immediately after intravitreal and supraciliary injection were compared.
  
  
  RESULTS
  Supraciliary delivery of both sulprostone and brimonidine reduced IOP by as much as 3 mm Hg bilaterally in a dose-related response; comparison with topical administration at the conventional human dose showed approximately 100-fold dose sparing by supraciliary injection for both drugs. A safety study showed that the kinetics of IOP elevation immediately after supraciliary and intravitreal injection of placebo formulations were similar.
  
  
  CONCLUSIONS
  This study introduced the use of targeted drug delivery to the supraciliary space by using a microneedle and demonstrated dramatic dose sparing of antiglaucoma therapeutic agents compared to topical eye drops. Targeted delivery in this way can increase safety by reducing side effects and could allow a single injection to contain enough drug for long-term sustained delivery.
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: 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: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007429:Intraocular Pressure / Q000187:drug effects* / Q000235:genetics*; D058449:Intravitreal Injections; D008297:Male; D008904:Miniaturization; D009339:Needles; D011817:Rabbits
chemical_list: D000959:Antihypertensive Agents
keywords: drug delivery; glaucoma; microneedle; suprachoroidal