U. Pleyer et al., OCULAR ABSORPTION OF CYCLOSPORINE-A FROM LIPOSOMES INCORPORATED INTO COLLAGEN SHIELDS, Current eye research, 13(3), 1994, pp. 177-181
We investigated the ability of liposomes to deliver the immunosuppress
ive agent cyclosporine A (CsA) to the cornea, anterior sclera, aqueous
humor, and vitreous in rabbit eyes. One drop (10 mu l) of liposome-en
capsulated CsA (CsA-LIP) or olive oil drops containing an equivalent c
oncentration of CsA (CsA-DR) were administered at 15- minute intervals
within the first hour and then one hourly over a 6-hour period. In ad
dition, collagen shields soaked for 30 minutes in the liposome prepara
tion (CsA-LIP-CS) were tested in vitro and in vivo as a new drug deliv
ery approach. CsA levels were measured by fluorescence-immunoassay aft
er 1, 3, or 6 hours of drug administration. CsA levels in this study w
ere 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 pe
aked 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 cor
nea and sclera at 1 and 3 hours than CsA-DR. In aqueous and vitreous h
umor, CsA levels increased from 1 to 6 hours in animals receiving eith
er CsA-DR or CsA-LIP. On the other hand, animals receiving a single ap
plication 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 sign
ificantly higher levels of CsA in aqueous and vitreous humor at 1, 3,
and 6 hours than animals receiving CsA-DR. Moreover, animals receiving
CsA-CS-LIP had higher CsA levels in aqueous humor at 1 and 3 hours th
an animals receiving CsA-LIP, CsA was not detectable in the serum of r
abbits in any treatment group. These results demonstrate that liposome
-encapsulated CsA is an effective means of intraocular drug delivery.
The combination of liposome-encapsulated CsA with collagen shields may
offer a new drug device for the eye.