title: Fluorescence investigation of the retinal delivery of hydrophilic compounds via liposomal eyedrops.
abstract: We examined the feasibility of using submicron-sized liposomes (ssLips) for retinal delivery of hydrophilic compounds, which would also have a wide range of applications. To evaluate the uptake into conjunctival cell line and the intraocular behavior of hydrophilic compound-containing ssLips after eyedrop application, fluorometric investigation was carried out by using a hydrophilic fluorescence probe, 5(6)-carboxyfluorescein (CF). A relatively high amount of CF (>50%) could be incorporated into an internal phase of ssLips by a calcium acetate gradient method. CF being entrapped within the liposomes markedly enhanced both the uptake of CF into conjunctival cells and CF-oriented emission in the retina in mice after eyedrop application, while the free CF did not clear delivery efficiency in both in vitro and in vivo study. In addition, the cellular uptake and luminescence intensity in the retina were higher when a ssLip formulation composed of L-α-distearoyl phosphatidylcholine was applied than when a ssLip formulation composed of egg phosphatidylcholine was applied. Consequently, ssLips of appropriate composition were considered to have good potential to carry hydrophilic compounds into the retina.
authors.affiliation: Department of Drug Delivery Technology and Science, Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hironaka
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
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: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000085:Acetates / Q000737:chemistry; D000818:Animals; D001692:Biological Transport; D017610:Calcium Compounds / Q000737:chemistry; D002460:Cell Line; D003228:Conjunctiva / Q000166:cytology / Q000378:metabolism*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005240:Feasibility Studies; D005452:Fluoresceins / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007202:Indicators and Reagents / Q000737:chemistry; D008081:Liposomes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics; D010713:Phosphatidylcholines / Q000737:chemistry; D012160:Retina / Q000166:cytology / Q000378:metabolism*
chemical_list: D000085:Acetates; D017610:Calcium Compounds; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008081:Liposomes; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D010713:Phosphatidylcholines; C024098:6-carboxyfluorescein; C010942:1,2-distearoyllecithin; C120662:calcium acetate