title: Retinal drug delivery using eyedrop preparations of poly-L-lysine-modified liposomes.
abstract: The purpose of this study was to develop surface-modified liposomes that enhance the efficiency of eye drop drug delivery to the retina. Various molecular weights and concentrations of the water-soluble cationic polymer poly-L-lysine (PLL) were used to modify the surface of submicronized (100 nm) liposomes. Physicochemical properties of surface-modified liposomes were determined in vitro, and the efficiency of drug delivery to the retina was investigated in vivo. Using coumarin-6 as a model drug and fluorescent marker, we show that liposome surface modification by PLL dramatically increased delivery to mouse retina segments after eye drop administration. However, when PLL of high molecular weight (>30,000) was used at higher concentrations (>0.05%), aggregation of surface-modified liposomes increased particle size and hampered distribution to inner ocular tissues. As a result, the efficiency of drug delivery of these aggregated surface-modified liposomes was the same as unmodified liposomes. The optimal molecular weight and concentration of PLL in drug-delivering liposomes were 15,000-30,000 and 0.005%, respectively. Under these conditions, PLL-modified liposomes were not cytotoxic in corneal or conjunctival cells. In conclusion, surface-modified liposomes have great potential as effective retinal drug delivery carriers in eye drop formulations.
authors.affiliation: Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Keiichi
authors.initials: K
authors.lastname: Karasawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Hironaka
authors.forename: Kohei
authors.initials: K
authors.lastname: Tahara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D008081:Liposomes; D008297:Male; D051379:Mice; D009883:Ophthalmic Solutions; D011107:Polylysine / Q000737:chemistry*; D012160:Retina
chemical_list: D008081:Liposomes; D009883:Ophthalmic Solutions; D011107:Polylysine