title: Laser-induced intrachoroidal dexamethasone drug delivery system to posterior eye segment.
abstract: OBJECTIVE
  To investigate the feasibility of laser-induced intrachoroidal dexamethasone (DEX) delivery as a potentially useful therapy for adjusting the most effective drug level to the posterior segment eye diseases.
  
  
  METHODS
  An implant was prepared by dissolving poly(DL-lactide) and DEX. In vitro release of DEX was evaluated at 7, 14, and 28 days by ELISA. In vivo, a DEX implant was inserted into a rabbit choroid, and 10, 50, or 200 burns of photocoagulation were applied at the implant lesion. After treatment, the vitreous humor was immediately aspirated and the DEX level was measured by liquid chromatography/mass spectrometry/mass spectrometry. Furthermore, the vitreous DEX level was measured at 1, 7, 14, and 28 days after implantation and 50 burns of photocoagulation. The toxicity of the laser-induced DEX implant was evaluated by ophthalmoscopy and light microscopy. Endotoxin-induced uveitis (EIU) was induced after DEX implantation and photocoagulation, and anti-inflammatory activities were evaluated by grading clinical signs, protein concentrations, and histopathologic studies.
  
  
  RESULTS
  Photocoagulation significantly increased the DEX release from the implant at 7 days in vitro. In vivo, the DEX implant exposed to 10, 50, and 200 burns of photocoagulation increased the vitreous DEX levels in a dose-dependent manner. The vitreous DEX level in the DEX implant applied to 50 burns of photocoagulation peaked 1 day after treatment. The laser-induced DEX implant showed no retinal abnormalities except the implantation site, and significantly inhibited the EIU.
  
  
  CONCLUSIONS
  Laser-induced intrachoroidal DEX delivery controls the DEX level in the vitreous humor and effectively prevents the experimental uveitis.
authors.affiliation: Murata Eye Clinic, Morioka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Murata
authors.forename: Atushi
authors.initials: A
authors.lastname: Sanbe
authors.forename: Jung Wha
authors.initials: JW
authors.lastname: Lee
authors.forename: Hideo
authors.initials: H
authors.lastname: Nishigori
mesh_terms: D000818:Animals; D001682:Biological Availability; D002829:Choroid / Q000187:drug effects* / Q000601:surgery; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017075:Laser Coagulation; D008070:Lipopolysaccharides; D009887:Ophthalmoscopy; D011817:Rabbits; D053719:Tandem Mass Spectrometry; D015866:Uveitis, Posterior / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D008070:Lipopolysaccharides; D003907:Dexamethasone
keywords: dexamethasone; drug delivery system; intrachoroidal implantation; photocoagulation; uveitis