title: Therapeutic effect of stealth-type polymeric nanoparticles with encapsulated betamethasone phosphate on experimental autoimmune uveoretinitis.
abstract: OBJECTIVE
  The therapeutic effects of betamethasone phosphate (BP) encapsulated in biocompatible and biodegradable blended nanoparticles of poly(lactic acid) (PLA) homopolymers and PEG-block-PLA copolymers (stealth nanosteroids) were examined in an experimental autoimmune uveoretinitis (EAU) model in Lewis rats.
  
  
  METHODS
  EAU was induced by S-antigen peptide in Lewis rats. Accumulation of systemically administered Cy7-labeled stealth nanoparticles in inflamed eyes of rats with EAU was assessed using in vivo fluorescence imaging, and the therapeutic effect of stealth nanosteroids, nonstealth nanosteroids, or saline on EAU was examined. The eyes were obtained 7 days after the treatment, and the histologic score was determined using pathologic findings. The expression of inflammatory cytokines including IL-6, IL-17, and VEGF was determined immunohistochemically.
  
  
  RESULTS
  Cy7-stealth nanoparticles accumulated in inflamed eyes of rats with EAU and remained in situ for a 3-day period. Systemically administered stealth nanosteroids (100 μg of BP) reduced the clinical scores of rats with EAU within 1 day and maintained the effect for 2 weeks. This treatment also decreased the histologic scores and the expression of inflammatory cytokines in the retina of EAU.
  
  
  CONCLUSIONS
  The strong therapeutic benefit on EAU obtained with the stealth nanosteroids may have been due to prolonged blood circulation and targeting to the inflamed uvea and retina, in addition to sustained release in situ.
authors.affiliation: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan. tstmski@jikei.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sakai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ishihara
authors.forename: Megumu
authors.initials: M
authors.lastname: Higaki
authors.forename: Goichi
authors.initials: G
authors.lastname: Akiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001672:Biocompatible Materials; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D018613:Microscopy, Confocal; D053758:Nanoparticles; D011091:Polyesters; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014018:Tissue Distribution; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C028994:betamethasone sodium phosphate; D001623:Betamethasone