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

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Bioactive Materials 2022年第3期7卷 77-91页

作者： Yi Han Lu Jiang Huihui Shi Chenfang Xu Minting Liu Qingjian Li Lan Zheng Hong Chi Mingyue Wang Zuguo Liu Mingliang You Xian Jun Loh Yun-Long Wu Zibiao Li Cheng Li Fujian Provincial Key Laboratory of Ophthalmology and Visual Science&ocular Surface and Corneal Diseases Eye Institute&Affiliated Xiamen Eye CenterSchool of MedicineXiamen UniversityXiamen361102China Institute of Materials Research and Engineering A*STAR(Agency for ScienceTechnology and Research)Singapore138634Singapore School of Chemical Sciences University of Chinese Academy of ScienceBeijing100049China Key Laboratory of Marine Materials and Related Technologies Zhejiang Key Laboratory of Marine Materials and Protective TechnologiesNingbo Institute of Material Technology and EngineeringChinese Academy of ScienceNingbo315201China Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology School of Pharmaceutical SciencesXiamen UniversityXiamen361102China Hangzhou Cancer Institute Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang ProvinceAffiliated Hangzhou Cancer HospitalZhejiang University School of MedicineHangzhou310002China Shandong Provincial Key Laboratory of Molecular Engineering School of Chemistry and Pharmaceutical EngineeringQilu University of Technology(Shandong Academy of Sciences)Jinan250353China Department of Materials Science and Engineering National University of SingaporeSingapore117575Singapore

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.

关键词： Ocular adhesive Polyhedral oligomeric silsesquioxane FK506 Dry eye

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