title: Systemic treatment with glutathione PEGylated liposomal methylprednisolone (2B3-201) improves therapeutic efficacy in a model of ocular inflammation.
abstract: OBJECTIVE
  Ocular inflammation is associated with the loss of visual acuity and subsequent blindness. Since their development, glucocorticoids have been the mainstay of therapy for ocular inflammatory diseases. However, the clinical benefit is limited by side effects due to the chronic use and generally high dosage that is required for effective treatment. We have developed the G-Technology to provide a means for sustained drug delivery, increased drug half-life, and reduced bodily drug exposure. Glutathione PEGylated liposomal methylprednisolone (2B3-201) has been developed as treatment for neuroinflammatory conditions and was evaluated in ocular inflammation.
  
  
  METHODS
  The efficacy of 2B3-201 was investigated in rats with experimental autoimmune uveitis (EAU). Rats received 10 mg/kg of 2B3-201 intravenously at disease onset and at peak of the disease. The same dose of free methylprednisolone served as control treatment. Clinical signs of ocular inflammation were assessed by slit-lamp and immunohistochemistry.
  
  
  RESULTS
  Whereas free methylprednisolone was ineffective, two doses of 2B3-201 almost completely abolished clinical signs of EAU. This was corroborated further by immunohistochemical analyses of isolated eyes. Treatment with 2B3-201 significantly reduced the infiltration of inflammatory cells and subsequent destruction of the retina cell layers.
  
  
  CONCLUSIONS
  In this study, we show that systemic treatment with 2B3-201, a glutathione PEGylated liposomal methylprednisolone formulation, resulted in a superior efficacy in rats with EAU. Altogether, our findings hold promise for the development of a safe and more convenient systemic treatment for uveitis.
authors.affiliation: to-BBB technologies BV, Leiden, The Netherlands.
authors.forename: Arie
authors.initials: A
authors.lastname: Reijerkerk
authors.forename: Chantal C M
authors.initials: CC
authors.lastname: Appeldoorn
authors.forename: Jaap
authors.initials: J
authors.lastname: Rip
authors.forename: Marco
authors.initials: M
authors.lastname: de Boer
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Gaillard
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004338:Drug Combinations; D005938:Glucocorticoids / Q000008:administration & dosage; D005978:Glutathione / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008081:Liposomes; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D051381:Rats; D011917:Rats, Inbred Lew; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D004338:Drug Combinations; D005938:Glucocorticoids; D008081:Liposomes; D005978:Glutathione; D008775:Methylprednisolone
keywords: drug targeting; inflammation; liposome; methylprednisolone; uveitis