A temperature-sensitive gel of pranoprofen with stable tear film, anti-inflammatory, and sustained-release effects for alleviating dry eye symptoms.

Abstract

Dry eye disease (DED) treatment has increasingly focused on maintaining tear film stability and reducing ocular inflammation. In recent years, clinical studies have found that pranoprofen (PF), a non-steroidal anti-inflammatory drug, can also be used to treat DED with significant efficacy. In this study, we developed a pranoprofen thermosensitive gel (PF-TSG) formulated with Poloxamer 407/188 as hydrogel matrices. In vitro characterization confirmed the PF-TSG's compliance with ophthalmic formulation standards, including physiochemical parameters (transparent appearance, pH 7.2-7.4, gelation at 34 °C) and sustained-release behavior (91.03 ± 1.84 % cumulative release over 8 h). In vivo studies demonstrated that the gel significantly enhanced tear secretion, reduced corneal damage, and lowered conjunctival inflammation markers (TNF-α, IL-1β). The gel also extended the retention time of the drug in ocular tissues (aqueous humor > cornea > vitreous body). Pharmacokinetic analysis in rabbits revealed that the area under the curve (AUC) for PF in the aqueous humor was 1.85 times higher than that of the eye drop formulation. The PF-TSG achieves targeted drug delivery through thermo-responsive behavior, providing sustained anti-inflammatory effects, promoting corneal repair, and stabilizing the tear film. This formulation significantly enhances drug bioavailability in ocular target tissues and offers a promising novel strategy for DED treatment.