Ocular absorption of cyclosporine A from liposomes incorporated into collagen shields.
We investigated the ability of liposomes to deliver the immunosuppressive agent cyclosporine A (CsA) to the cornea, anterior sclera, aqueous humor, and vitreous in rabbit eyes. One drop (10 microliters) of liposome-encapsulated CsA (CsA-LIP) or olive oil drops containing an equivalent concentration of CsA (CsA-DR) were administered at 15-minute intervals within the first hour and then one hourly over a 6-hour period. In addition, collagen shields soaked for 30 minutes in the liposome preparation (CsA-LIP-CS) were tested in vitro and in vivo as a new drug delivery approach. CsA levels were measured by fluorescence-immunoassay after 1, 3, or 6 hours of drug administration. CsA levels in this study were highest in cornea and anterior sclera. In animals receiving either CsA-DR or CsA-LIP, CsA levels generally increased from 1 to 6 hours. In animals receiving a single application of CsA-CS-LIP, CsA levels peaked at 3 hours and declined at 6 hours in cornea and sclera. CsA-LIP and CsA-CS-LIP delivered significantly higher levels of CsA to the cornea and sclera at 1 and 3 hours than CsA-DR. In aqueous and vitreous humor, CsA levels increased from 1 to 6 hours in animals receiving either CsA-DR or CsA-LIP. On the other hand, animals receiving a single application of CsA-CS-LIP had lower levels of CsA at 6 hours than at the earlier time points. Animals receiving CsA-LIP or CsA-CS-LIP had significantly higher levels of CsA in aqueous and vitreous humor at 1, 3, and 6 hours than animals receiving CsA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)
Pleyer
U
U
Jules Stein Eye Institute, Department of Ophthalmology UCLA School of Medicine.
Elkins
B
B
Rückert
D
D
Lutz
S
S
Grammer
J
J
Chou
J
J
Schmidt
K H
KH
Mondino
B J
BJ
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000378:metabolism*; D001684:Biological Dressings; D003094:Collagen; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D007118:Immunoassay; D008081:Liposomes; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism*
D004337:Drug Carriers; D008081:Liposomes; D016572:Cyclosporine; D003094:Collagen