Trehalose-modulated poloxamer 407 thermosensitive hydrogel: sol-gel transition regulation and sustained low-dose pilocarpine nitrate delivery.

Traditional ophthalmic solutions and viscous gels are limited by insufficient precorneal residence time, inaccurate dosing administration, and inconvenient sterile filtration. Pilocarpine, originally a classic muscarinic acetylcholine receptor agonist for glaucoma management, has been recently repurposed for presbyopia treatment; however, its clinical application is greatly restricted by frequent severe ocular adverse reactions, including xerophthalmia and conjunctival hyperemia. Herein, trehalose was adopted to modify poloxamer 407 thermosensitive hydrogel, on the basis of its dual functions of tuning gel physicochemical properties and enhancing cellular desiccation resistance. The incorporation of trehalose lowered the critical gelation threshold concentration of poloxamer 407 without impairing the intrinsic physicochemical properties of the hydrogel. The optimized formulation exists as a low-viscosity aqueous solution (approximately 50 mPa·s) at ambient temperature, which allows convenient sterilization via 0.22 μm filtration, and rapidly undergoes in-situ sol-gel transition on the ocular surface to form isotonic hydrogel. This hydrogel protects loaded pilocarpine against hydrolytic degradation and improves corneal hydration. In vivo rabbit ocular irritation tests verified that the formulation effectively alleviates pilocarpine-induced ocular irritation. Benefiting from excellent thermal stability and industrial processability, this delivery system exhibits promising translational prospects and lays a solid foundation for follow-up clinical research on presbyopia treatment.