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

Abstract

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.

Anti‐Oxidative and Anti‐Inflammatory Micelles: Break the Dry Eye Vicious Cycle

“…[ 1 , 2 ] Currently, DED affects ≈30% of the world's population and has become the most common ocular surface disease worldwide, posing an enormous economic burden to society. [ 3 , 4 ] Although the pathogenesis of DED remains only partially elucidated, inflammation, as the consequence of both earlier innate immune response and following adaptive response, has been identified as a critical contributor that can initiate dry eye's vicious cycle. The vicious cycle refers to a malignant development interacted among inflammation, hyperosmolarity, cell apoptosis, and tear film decline that deteriorates dry eye syndrome.…”

Updates on Biodegradable Formulations for Ocular Drug Delivery

“…Tacrolimus is another widely used immunosuppressant for DED treatment. Biodegradable formulations of tacrolimus, such as cationic liposome [ 113 ] and thermoresponsive in situ gel formulations [ 114 ] have been developed to improve ocular retention, enhance corneal tacrolimus concentration, and decrease levels of reactive oxygen species and inflammatory factors associated with DED ( Table 1 ).…”

Recent developments of temperature‐responsive polymers for ophthalmic applications

“…We have also reported the use of a thermogelling copolymer consisting of PEG, PPG, and monofunctional polyhedral oligomeric silsesquioxane (MPOSS) to treat dry eye. 141 Compared to commercial FK506 eye drops, the poly(MPOSS-PEG-PPG urethane) (MPEP) hydrogel can encapsulate FK506 in its hydrophobic micellar core and improve its water solubility. The POSS component helped to improve the adhesion of the thermogel to the ocular surface by enhancing its binding affinity to mucin.…”