title: Chitosan nanoparticles as new ocular drug delivery systems: in vitro stability, in vivo fate, and cellular toxicity.
abstract: OBJECTIVE
  To assess the potential of chitosan (CS) nanoparticles for ocular drug delivery by investigating their interaction with the ocular mucosa in vivo and also their toxicity in conjunctival cell cultures.
  
  
  METHODS
  Fluorescent (CS-fl) nanoparticles were prepared by ionotropic gelation. The stability of the particles in the presence of lysozyme was investigated by determining the size and their interaction with mucin, by measuring the viscosity of the mucin dispersion. The in vivo interaction of CS-fl nanoparticles with the rabbit cornea and conjunctiva was analyzed by spectrofluorimetry and confocal microscopy. Their potential toxicity was assessed in a human conjunctival cell line by determining cell survival and viability.
  
  
  RESULTS
  CS-fl nanoparticles were stable upon incubation with lysozyme and did not affect the viscosity of a mucin dispersion. In vivo studies showed that the amounts of CS-fl in cornea and conjunctiva were significantly higher for CS-fl nanoparticles than for a control CS-fl solution, these amounts being fairly constant for up to 24 h. Confocal studies suggest that nanoparticles penetrate into the corneal and conjunctival epithelia. Cell survival at 24 h after incubation with CS nanoparticles was high and the viability of the recovered cells was near 100%.
  
  
  CONCLUSIONS
  CS nanoparticles are promising vehicles for ocular drug delivery.
authors.affiliation: Deptamento de Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Campus Sur. Universidad de Santiago de Compostela, 15706 Santiago de Compostela, Spain.
authors.forename: Angela M
authors.initials: AM
authors.lastname: de Campos
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Diebold
authors.forename: Edison L S
authors.initials: EL
authors.lastname: Carvalho
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sánchez
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Alonso
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D048271:Chitosan / Q000737:chemistry / Q000633:toxicity*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems; D004355:Drug Stability; D019793:Fluorescein; D008297:Male; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009077:Mucins / Q000737:chemistry / Q000378:metabolism; D009113:Muramidase / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits
chemical_list: D009077:Mucins; D048271:Chitosan; D009113:Muramidase; D019793:Fluorescein