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 ...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.展开更多
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].
文摘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.
