title: Physicochemical properties affecting retinal drug/coumarin-6 delivery from nanocarrier systems via eyedrop administration.
abstract: OBJECTIVE
  To elucidate the effect of physicochemical properties of nanocarrier systems on drug delivery efficiency to the retina by eyedrop administration in mice, rabbits, and monkeys.
  
  
  METHODS
  Submicron-sized liposomes (ssLips) of different particle size, cholesterol content, surface charge, and multilamellar vesicles (MLV) were prepared by the hydration
  
  
  METHODS
  Fluorescence probe (coumarin-6)-incorporated liposomes, lipid emulsions, and FITC-labeled polystyrene particles were used to investigate their intraocular behavior after eyedrop administration, using epifluorescence microscopy in mice, rabbits, and monkeys.
  
  
  RESULTS
  Delivery efficiency of fluorescent probes to the mouse retina from dropped liposomes was extensively improved by reducing their particle size (<600 nm) and cholesterol content, whereas negligible improvement was observed in the case of MLV. Furthermore, FITC-labeled polystyrene particles and coumarin-6-incorporated lipid emulsions showed an insufficient effect on retinal delivery in mice even if their size was controlled at 110 nm. The highest accumulation of the fluorescent probe in the retina was observed around 30 minutes with any type of ssLip used, followed by the prompt disappearance of their fluorescence within 120 minutes in mice. Changes in the fluorescence intensity of coumarin-6 in rabbits and monkeys were observed in a manner similar to that described in mice. Retinal flat-mount images suggest that coumarin-6 incorporated in ssLip diffused from the iris and ciliary body side to the optic disc side in the retina after eyedrop administration.
  
  
  CONCLUSIONS
  The delivery efficiency of coumarin-6 to the retina was altered depending on particle size, constituents, and rigidity. ssLips with appropriate features would be promising drug carriers for retinal delivery through eyedrops.
authors.affiliation: Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Inokuchi
authors.forename: Kohei
authors.initials: K
authors.lastname: Hironaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D003374:Coumarins / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004655:Emulsions; D008081:Liposomes; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D009883:Ophthalmic Solutions; D010316:Particle Size; D011817:Rabbits; D012160:Retina / Q000187:drug effects*; D013844:Thiazoles / Q000008:administration & dosage*
chemical_list: D003374:Coumarins; D004655:Emulsions; D008081:Liposomes; D009883:Ophthalmic Solutions; D013844:Thiazoles; C517282:coumarin 6