The low bioavailability and consequently the poor therapeutic response of traditional ophthalmic formulations is caused by reduced pre-corneal residence time of the formulation in contact with the ocular surface. The use of colloidal carrier systems, namely lipid nanoparticles in combination with in situ gelling polymers, is an excellent strategy which results in the exponential increase of the bioavailability of ophthalmic drugs. In the present study, we have developed thermoresponsive eyedrops prepared with nanostructured lipid carriers (NLC) dispersions for the controlled delivery of ibuprofen. Lipid solubility studies and DSC measurements have proved that the lipids solubilise ibuprofen and present a good compatibility. NLC were prepared based on the melt-emulsification and ultrasonication technique and lipid nanoparticles with a Z-average of 120-150 nm, polydispersity index below 0.3, highly positive zeta potential and an efficacy of encapsulation of ~87% were obtained. The cytotoxicity of NLC was evaluated by the Alamar Blue reduction assay using the Y-79 human retinoblastoma cell line, and no relevant toxicity was observed after exposure to 0-100 μg/mL NLC for up to 72 hours. The HET-CAM assay was used to assess the product eye compatibility, confirming that the developed product does not exhibit irritant potential. The in vitro release studies showed ibuprofen release over several hours.