Enhanced Ocular Delivery of Tacrolimus via Cationic Nanoliposomes: Mitigating Inflammation and Rebalancing Th17/Treg Responses in Dry Eye Disease

Dry eye disease (DED) is a common ocular surface disorder characterized by persistent inflammation and immune imbalance, leading to visual impairment and substantial deterioration in quality of life. Although topical medications remain the mainstay of DED management, their therapeutic effectiveness is frequently limited by poor corneal penetration, low ocular bioavailability, and potential safety issues associated with long-term administration. To address this, we engineered a low-dose cationic tacrolimus nanoliposome delivery system (FK506 NLPs) designed to enhance ocular surface drug availability while targeting immune-inflammatory dysregulation. The positively charged NLPs exhibited prolonged corneal residence via mucoadhesion and improved drug permeation. In a murine model of DED, FK506 NLPs accelerated ocular surface repair, improved tear film stability, and preserved conjunctival goblet cells and lacrimal gland structure. Mechanistically, they suppressed the expression of key proinflammatory mediators in both corneal and lacrimal tissues and restored immune homeostasis by re-establishing the balance between Th17 and regulatory T cells. Importantly, FK506 NLPs also exhibited favorable in vivo biocompatibility. Taken together, these findings demonstrated that FK506 NLPs combined improved ocular delivery with coordinated anti-inflammatory and immunoregulatory effects, highlighting their potential as a promising therapeutic strategy for the management of DED.