Effectiveness of an ocular adhesive polyhedral oligomeric silsesquioxane hybrid thermo-responsive FK506 hydrogel in a murine model of dry eye

Dry eye is a common ocular disease that results in discomfort and impaired vision,impacting an individual’s quality of life.A great number of drugs administered in eye drops to treat dry eye are poorly soluble in water and are rapidly eliminated from the ocular surface,which limits their therapeutic effects.Therefore,it is imperative to design a novel drug delivery system that not only improves the water solubility of the drug but also prolongs its retention time on the ocular surface.Herein,we develop a copolymer from mono-functional POSS,PEG,and PPG(MPOSS-PEG-PPG,MPEP)that exhibits temperature-sensitive sol-gel transition behavior.This thermo-responsive hydrogel improves the water solubility of FK506 and simultaneously provides a mucoadhesive,long-acting ocular delivery system.In addition,the FK506-loaded POSS hydrogel possesses good biocompatibility and significantly improves adhesion to the ocular surface.In comparison with other FK506 formulations and the PEG-PPG-FK506(F127-FK506)hydrogel,this novel MPOSS-PEG-PPG-FK506(MPEP-FK506)hydrogel is a more effective treatment of dry eye in the murine dry eye model.Therefore,delivery of FK506 in this POSS hydrogel has the potential to prolong drug retention time on the ocular surface,which will improve its therapeutic efficacy in the management of dry eye.