Topical treatment of tyrosine kinase 2 inhibitor through borneol-embedded hydrogel:Evaluation for preventive,therapeutic,and Recurrent management of psoriasis  

作　　者：Yuhsien Lai Xuesong Wu Zhuoyu Jiang Yifei Fang Xiuting Liu Dan Hong Yanyun Jiang Guozhen Tan Shiqi Tang Siyao Lu David Wei Sam T.Hwang Kit S.Lam Liangchun Wang Yanyu Huang Zhenrui Shi 

机构地区：[1]Department of Dermatology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,510120,China [2]Department of Dermatology,University of California-Davis,Sacramento,CA,95817,USA [3]School of Biomedical Engineering,Sun Yat-sen University,518107,China [4]Department of Biochemistry and Molecular Medicine,University of California-Davis,Sacramento,CA,95817,USA

出　　处：《Bioactive Materials》2024年第11期83-95,共13页生物活性材料（英文）

基　　金：National Natural Science Foundation of China[grant number 82203906];Guangdong Basic and Applied Basic Research Foundation[grant number 2022A1515012020];Project of Guangzhou Science and Technology[grant number 202201020355].

摘　　要：Psoriasis,an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course,continues to be primarily managed through topical therapy.While oral administration of tyrosine kinase 2 inhibitors(TYK2i)stands as an effective approach for psoriasis treatment,the potential efficacy of topical application of TYK2i remains unexplored.Herein,the carbomer/alginic acid hydrogel is embedded with borneol(BO)as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy.The hydrogel system,i.e.,TYK2i-BO-gel,exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis,as evidenced by phenotypical images,psoriasis severity score index(PSI),histology,immunohistochemical staining,and PCR analysis.Remarkably,TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50%reduction in ear thickness changes(p<0.0001),PSI(p<0.0001)and epidermal thickness(p<0.05).Moreover,a strengthened anti-inflammatory effect caused by TYK2i-BO-gel is seen in a human skin explant model,implying its potential application for human patients.With the addition of BO,the TYK2i-BO-gel not only increases skin permeability but also inhibits the expression of antimicrobial peptides in keratinocytes and facilitates the anti-Th17 response of TYK2i with suppressed activation of STAT3.Therefore,this work represents the accessibility and effectiveness of TYK2i-BO-hydrogel as a new topical formulation for anti-psoriasis management and shows great potential for clinical application.

关 键 词：PSORIASIS Topical hydrogel Transdermal delivery Tyrosine kinase 2 inhibitor BORNEOL 

分 类 号：R758.63[医药卫生—皮肤病学与性病学] TQ427.26[医药卫生—临床医学]