Macro-to-nano dynamic hydrogels in sustained transdermal therapy of diffuse ocular surface malignancies  

作　　者：Jie Chen Yirong Zeng Hao Tian Qixiao Guan Ziyue Huang Hongjing Dou Shiqiong Xu Renbing Jia 

机构地区：[1]Department of Ophthalmology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China [2]Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology,Shanghai 200011,China [3]The State Key Laboratory of Metal Matrix Composites,School of Materials Science and Engineering,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Nano Research》2025年第3期372-385,共14页纳米研究(英文版)

基　　金：supported by grants from the Science and Technology Commission of Shanghai(No.22Y31900700);Program of Innovative Research Team of High-Level Local Universities in Shanghai(No.SHSMU-ZDCX20210902);Shanghai Municipal Health Commission(No.2022YQ01);“New Star of Medical College”Young Medical Talents Training Program in Shanghai in 2020 and Cross-Disciplinary Research Fund Project of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(No.JYJC202303).

摘　　要：Conjunctival melanoma(CοM)is of high malignancy that diffusely impacts the ocular surface,which is challenging to surgically remove and pose a life-threatening risk.As one of the most suitable treatment options,drug dropping drugs to the eye surface,however,is limited in its clinical application for CoM treatment due to low drug utilization.Using BRAF/MEK inhibitors(BRAF/MEKi)as model drugs,this study proposes a long-lasting eyedrop based on BRAF/MEK dual-targeted liposome-doped dynamic hydrogels with drugs(B/MLDDHs),which can overcome the tear flushing to succeed in effective ocular surface drug delivery.B/MLDDHs encapsulate drugs within lipid bilayers,enhancing drug bioavailability and biocompatibility.The aldehyde dextran and protonated chitosan-based injectable hydrogel system facilitates drug retention on the ocular surface exerting a sustained liposome release,which significantly enhances the drug bioavailability.In therapeutics,this study demonstrates significantly enhanced in vivo therapeutic effect on orthotopic mouse model of CoM.Given their ability to fulfill permeable and long-term release of hydrophobic drugs,B/MLDDHs may serve as a promising platform for non-invasive delivery of various drug molecules,thereby improving therapeutic outcomes for CoM.

关 键 词：HYDROGELS targeted therapy conjunctival melanoma ocular surface malignancies 

分 类 号：R730.5[医药卫生—肿瘤]