Topical liposome-encapsulated FK506 for the treatment of endotoxin-induced uveitis.
OBJECTIVE
Liposome preparations of FK506 improve the penetration of topically administered drug into the aqueous humor. The purpose of the experiment was to compare topically administered highdose oil-dissolved FK506 (OD-FK506) and low-dose liposome-bound FK506 (LB-506) for the treatment of endotoxin-induced uveitis (EIU).


METHODS
Endotoxin-induced uveitis was produced in female Lewis rats with Salmonella typhimurium endotoxin. Four hours prior to endotoxin injection, one eye received 20 mul eyedrops every four hours containing either high-dose OD-FK506 at 3 mg/ml (N = 20), low-dose LB-FK506 at 0.16 mg/ml (N = 19), prednisolone acetate 1% (N = 20), or empty liposomes (N = 20). Eyes were enucleated 24 hours after endotoxin injection and inflammatory cells were counted on histologic sections by two masked observers.


RESULTS
The mean number of infiltrating inflammatory cells per section +/- S.E.M. was 127.8 +/- 20.1, 76.8 +/- 16.7, 75.0 +/- 19.1, and 3.6 +/- 0.4 for animals treated with empty liposomes, LB-FK506, OD-FK506, and prednisolone acetate, respectively. The difference in inflammation between the empty liposome controls and the LB-FK506- and OD-FK506-treated animals was statistically significant (p = 0.03 and p = 0.02, respectively). The difference in inflammation between the high-dose OD-FK506- and low-dose LB-FK506-treated animals was not statistically significant (0 = 0.94).


CONCLUSIONS
In this study, low-dose LB-FK506 and high-dose (OD-FK506) were both effective in inhibiting EIU. Higher concentrations of LB-FK506 are being developed and should augment the therapeutic effect of topical FK506.
Whitcup
S M
SM
National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1863, USA.
Pleyer
U
U
Lai
J C
JC
Lutz
S
S
Mochizuki
M
M
Chan
C C
CC
D000287:Administration, Topical; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004731:Endotoxins; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008081:Liposomes; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D014605:Uveitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology
D004337:Drug Carriers; D004731:Endotoxins; D007166:Immunosuppressive Agents; D008081:Liposomes; D016559:Tacrolimus