Tacrolimus cationic nanoemulsion enhances ocular surface retention for the treatment of dry eye disease and allergic conjunctivitis.

Tacrolimus (TAC), as a new potent immunosuppressant, holds promise for treating immune-mediated ocular surface diseases, especially in dry eye disease (DED) and allergic conjunctivitis (AC). However, the low water solubility of TAC results in commercial formulations (Talymus®) as suspensions with limited corneal retention time and low penetration efficiency. In addition, the irritation of TAC reflexes tearing and rapid drug clearance, thereby reducing bioavailability. To address these challenges, we developed a TAC cationic nanoemulsion (TAC-CNE) with good biocompatibility. The oil-phase encapsulation improved water solubility while reduced irritation of TAC, and enabled sustained drug release via diffusion kinetics. Furthermore, cationic surface modification promoted electrostatic interactions with negatively charged ocular mucin proteins. This interaction, combined with the appropriate viscosity, can prolong the ocular surface retention time and thereby improve bioavailability. In addition, TAC-CNE was prepared through a simple high-pressure homogenization method, exhibiting stability over 6 months under storage conditions. In vivo and in vitro evaluations demonstrated the superior therapeutic efficacy of TAC-CNE in DED and AC. In particular, TAC-CNE was more prominent in safety, which solved the problems of ocular irritation of commercial preparations. Our findings highlight TAC-CNE as a promising strategy to overcome the limitations of commercial formulations, offering a new treatment choice for DED and AC.