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Effective ocular delivery of tacrolimus remains challenging due to rapid clearance and low bioavailability. This study aimed to design an in situ gel incorporating tacrolimus-loaded solid lipid nanoparticles (TAC-SLNs) for improved therapeutic outcomes in immune conjunctivitis. The TAC-SLNs in situ gel was optimized and evaluated for particle morphology, size, surface charge, drug encapsulation efficiency, loading capacity, and release profile in vitro. Pharmacokinetic and pharmacodynamic studies were also performed in animal models to assess ocular retention and treatment efficacy. The TAC-SLNs in situ gel was prepared via homogenization followed by probe sonication, yielding nanoparticles with an average diameter of 122.3 ± 4.3 nm. Gelation did not significantly affect particle size. Rheological testing indicated pseudoplastic flow behavior, with viscosity increasing with temperature and forming a stable gel at 32°C. Drug release studies demonstrated sustained delivery both in vitro and in vivo. Animal experiments revealed enhanced pharmacodynamic performance of the in situ gel compared to TAC-SLNs alone or conventional eye drops, showing improved efficacy in reducing conjunctival inflammation. TAC-SLNs in situ gel offers a promising approach for ocular tacrolimus delivery, combining prolonged retention, controlled release, and enhanced therapeutic effect, highlighting its potential for managing immune conjunctivitis.
