Topical liposome-encapsulated FK506 for the treatment of endotoxin-induced uveitis

Abstract

Purpose: 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 high-dose 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 µl 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). Conclusion: 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.