title: Safety evaluation of nanoliposomes containing cyclosporine a after ocular administration.
abstract: OBJECTIVE
  Cyclosporine A (CyA) is an anti inflammatory drug which modulates immune system. We prepared two liposomal formulations of CyA for ophthalmic administration. In the present study, the safety of these formulations was tested in rabbits.
  
  
  METHODS
  Fusogenic and positively charged liposomes were prepared by solvent evaporation method. CyA concentration in ophthalmic preparations was 0.2% w/v. Twenty New Zealand albino rabbits (40 eyes) were divided into two groups. Right eyes were treated and left eyes served as control. Eyes were examined clinically in 1, 3, 7, 14 and 28th days of the study. Eleven eyes were enucleated for pathological evaluation at the end of the study.
  
  
  RESULTS
  Mean size and charge of positively charged and fusogenic liposomes were 110.7 ± 1.5 and 114.9 ± 15.2 nm; 19.0 ± 2.2 and 2.5 ± 0.5 mV, respectively. Clinically, there were transient conjunctival injections and corneal epithelial defects in a few cases which were not limited to the treated eyes. Positively charged liposomes caused conjunctival injection in two cases, while this complication occurred in only one eye after administration of fusogenic liposomes. Histopathological examination revealed the presence of follicular conjunctivitis in two eyes with conjunctival injection. Inflammation in cases received the fusogenic form of the drug was mild and non-specific.
  
  
  CONCLUSIONS
  The results of this study suggest that fusogenic liposomal preparation of CyA is safe and can be useful for future studies.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Navid
authors.initials: N
authors.lastname: Mosallaei
authors.forename: Touka
authors.initials: T
authors.lastname: Banaee
authors.forename: Mehdi
authors.initials: M
authors.lastname: Farzadnia
authors.forename: Ehsan
authors.initials: E
authors.lastname: Abedini
authors.forename: Hami
authors.initials: H
authors.lastname: Ashraf
authors.forename: Bizhan
authors.initials: B
authors.lastname: Malaekeh-Nikouei
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000633:toxicity*; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000633:toxicity*; D008081:Liposomes / Q000737:chemistry*; D049329:Nanostructures; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011817:Rabbits
chemical_list: D007166:Immunosuppressive Agents; D008081:Liposomes; D010714:Phosphatidylethanolamines; C094877:dioleoyl phosphatidylethanolamine; D015060:1,2-Dipalmitoylphosphatidylcholine; D016572:Cyclosporine; D002784:Cholesterol