Topical adhesive spatio-temporal nanosystem co-delivering chlorin e6 and HMGB1 inhibitor glycyrrhizic acid for in situ psoriasis chemo-phototherapy  

作　　者：Lijun Su Yixi Zhu Xuebo Li Di Wang Xiangyu Chen Zhen Liu Jingjing Li Chen Zhang Jinming Zhang 

机构地区：[1]State Key Laboratory of Southwestern Chinese Medicine Resources,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China [2]Department of Rehabilitation Sciences,Faculty of Health and Social Sciences,Hong Kong Polytechnic University,Hong Kong SAR 100872,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第2期1126-1142,共17页药学学报(英文版)

基　　金：supported by funding from the China Postdoctoral Science Foundation(Nos.2023T160071 and 2021M690488);Natural Science Foundation of Sichuan Province of China for Youths(No.2023NSFSC1768,China);The Science and Technology Development Fund(SKL-QRCM(UM)2023-2025,China);The State Key Laboratory of Quality Research in Chinese Medicine,University of Macao(No.SKL-QRCM-OP23020,China);The Central Guidance on Local Science and Technology Development Fund of Sichuan(23ZYZYTS0420,China);Multidisciplinary Evaluation of Southwest Characteristic TCM Resources Multidisciplinary Interdisciplinary Innovation Team(No.ZYYCXTD-D-202209,China).

摘　　要：Recently,photodynamic therapy(PDT)has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis.Unfortunately,the activation of high mobility group box 1 protein(HMGB1)by PDT triggers innate and adaptive immune responses,which exacerbate skin inflammation.Herein,we combined glycyrrhizic acid(GA),a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch.,with PDT actuated by the photosensitizer chlorin e6(Ce6)by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt(GC NPs/QCS-C).GC NPs/QCS-C exhibited high drug loading efficacy,uniform size distribution,an ideal topical adhesive property,enhanced skin retention and penetration in psoriasis-like lesions,and high intracellular uptake in epidermal cells compared with the counterparts.Subsequently,the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms,promoted the apoptosis of hyperproliferative epidermal cells,and alleviated the inflammatory cascade.The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation.Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

关 键 词：PSORIASIS Chitosan CATECHOL Spatio-temporal nanosystem Glycyrrhizic acid liposome Chemo-phototherapy Topical delivery ANTI-INFLAMMATION 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]