Tacrolimus-Loaded Cationic Nanoemulsion In-Situ Gel System: In-Vitro Characterization and Performance in a Dry-Eye Rabbit Model

Dry eye disease (DED) is a highly prevalent ocular surface disease that affects life quality and reduces productivity at work. The purpose of this study is to improve the efficacy of tacrolimus (FK506) in the treatment of DED using the special eye surface retention properties of cationic nanoemulsion (CNE) modified by thermosensitive in-situ gel (ISG) (CNE-ISG). The precorneal retention of CNE-ISG containing 0.05% FK506 (50 min) was longer than that of CNE containing 0.05% FK506 (25 min) and commercial suspension containing 0.1% FK506 (Talymus®) (10 min). Successfully modeled dry-eye rabbits were treated with 0.05% CNE-ISG (twice/day), 0.05% CNE and 0.1% suspension (Talymus®) (thrice/day). Schirmer's tear secretion test showed no significant difference between the CNE-ISG group and the healthy group after 5 days of treatment (p > 0.05). The results of a tear ferning test (TFT) showed that the tear-fern-like crystal branches in the CNE-ISG group returned to normal after 5 days of treatment. Histological analysis showed that the number of goblet cells in the CNE-ISG group significantly increased. HET-CAM stimulation test showed that the CNE-ISG group had no ocular irritation. The above results indicated that CNE-ISG might be a promising delivery system and as an effective dosage form was employed for FK506 in the treatment of DED.