Cross-linked thermosensitive nanohydrogels for ocular drug delivery with a prolonged residence time and enhanced bioavailability.

AIM: A temperature-triggered, cross-linked nano hydrogel formulation (NPs-gel) was prepared to prolong the residence time of dexamethasone (DXM) in the eye and increase its bioavailability. RESEARCH DESIGN AND METHODS: The NPs-gel was prepared by combining a high pressure homogenization method with a cold solution method. Soy lecithin E200, lecithin oil, glycerol, kolliphor P188, kolliphor P407, and polycarbophil were the excipients used for the formation of NPs-gel containing DXM. The nanoparticle size, temperature-sensitive phase transition characteristics, in vitro and in vivo release behavior, corneal permeability, and eye irritation level of the NPs-gel were evaluated. RESULTS: The NPs-gel had slightly larger particle size than the DXM-loaded nanoparticles, yet it retained the properties of nanoparticles such as surface effect and size effect. The phase transition temperature was 33.2 °C, which is within the trigger conditions of intraocular temperature. Under physiological conditions, the adhesion and adhesion work of the NPs-gel were 1.1 and 2.1 times that of an in situ-formed gel, and the gel strength of NPs-gel was 1.8 times that of an in situ-formed gel. These results indicate that NPs-gel has greater adhesion and mechanical strength. The area under the curve of NPs-gel was 3.08 and 1.51 times that of DXM-loaded nanoparticles and in situ-formed gel, showing higher bioavailability. CONCLUSION: The NPs-gel is a suitable formulation to further enhance ocular drug delivery.