CONTEXT: The nanogel combining cationic nanostructured lipid carriers (CNLC) and thermosensitive gelling agent could enhance preocular retention and ocular permeation capacity of curcumin (CUR). OBJECTIVE: The purpose of the study was to develop and characterize a thermosensitive ophthalmic in situ nanogel of CUR-CNLC (CUR-CNLC-GEL) and evaluate in vitro and in vivo properties of the formulations. MATERIALS AND METHODS: The physicochemical properties, in vitro release and corneal permeation, were evaluated. Ocular irritation and preocular retention capacity were also conducted. Finally, pharmacokinetic study in the aqueous humor was investigated by microdialysis technique. RESULTS: The solution-gel transition temperature of the optimized formulation diluted by simulated tear fluid was 34 ± 1.0 °C. The CUR-CNLC-GEL displayed zero-order release kinetics. The apparent permeability coefficient (Papp) and the area under the curve (AUC0→∞) of CUR-CNLC-GEL were 1.56-fold and 9.24-fold, respectively, than those of curcumin solution (CUR-SOL, p < 0.01). The maximal concentration (Cmax) was significantly improved (p < 0.01). The prolonged mean residence time (p < 0.01) indicated that CUR-CNLC-GEL is a controlled release formulation. DISCUSSION AND CONCLUSION: Those results demonstrated that CUR-CNLC-GEL could become a potential formulation for increasing the bioavailability of CUR in the aqueous humor by enhancing corneal permeation and retention capacity.