Background: Curcumin, a natural hydrophobic polyphenol, has been reported to have diverse pharmacological activities. Previous studies have evaluated its efficacy using both oral and transdermal dosage forms. However, two major obstacles-poor aqueous solubility and low stability-severely limited its pharmaceutical use.Objective: The main objective of this study was to prepare curcumin eye drops that provided sustained release to allow for once daily application in retinitis pigmentosa. Method: To achieve our goal, curcumin was complexed with β -cyclodextrin and hydroxypropyl-β- cyclodextrin in two molar ratios (1:1 and 1:2) using co-solvent, co-solvent with sonication and freezedrying filtration methods. A total of 12 complexes were prepared, then characterized using differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, solubility assessment and in vitro release studies. Results: An improvement in curcumin aqueous solubility relative to pure curcumin was achieved for all 12 complexes. However, the freeze-drying filtration method was superior to all other methods because it produced highly water-soluble drug-CD complexes. Based on our stability analyses, pH 6.8 phosphate buffer containing 1% Tween 80 was selected as the release medium for in vitro release studies because curcumin exhibited high stability in this medium. Our F11 formulation provided sustained release of the drug for more than 96 h with a maximum amount released of drug (21.77±0.26 μg/ml). Our in vitro release data also showed that release of drug from curcumin-CDs inclusion complexes followed a Higuchi non-Fickian diffusion mechanism. Conclusion: Based on these results, F11 was formulated as eye drops, which provide a promising once daily novel topical delivery of this naturally derived phytochemical.