机构:[1]School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.[2]State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.广东省中医院[3]Department of Dermatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.大德路总院皮肤科大德路总院皮肤科广东省中医院[4]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.深圳市中医院深圳医学信息中心
Rheumatoid arthritis (RA) is an autoimmune disease of synovial inflammation that affects populations worldwide. Transdermal drug delivery systems for treating RA have increased but remain challenging. We fabricated a dissolving microneedle (MN) system with photothermal (PT) polydopamine (PDA) to co-load the non-steroidal anti-inflammatory drug loxoprofen (Lox) and the Janus kinase inhibitor tofacitinib (Tof), with the aim of co-delivering Lox and Tof directly to the articular cavity, aided by the combination of MN and PT. In vitro and in vivo permeation studies showed that the PT MN significantly promoted drug permeation and retention in the skin. An in vivo visualization of the drug distribution in the articular cavity showed that the PT MN significantly promoted drug retention in the articular cavity. Importantly, compared to the intra-articular injection of Lox and Tof, the application of the PT MN to a carrageenan/kaolin-induced arthritis rat model exhibited superior performance in reducing joint swelling, muscle atrophy, and cartilage destruction. Furthermore, the PT MN downregulated the mRNA expression levels of proinflammatory cytokines, including TNF-α, IL-1β, iNOS, JAK2, JAK3, and STAT3. The results show that the PT MN transdermal co-delivery of Lox and Tof is a new synergetic therapy with high compliance and good therapeutic efficacy for RA.
基金:
The work was financially supported by the National Natural Science Foundation of China
(No. 82274109 and No. 81973491) and the Guangdong Basic and Applied Basic Research Foundation
(2022A1515010428).
第一作者机构:[1]School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
共同第一作者:
通讯作者:
通讯机构:[2]State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.[3]Department of Dermatology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.[4]Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
推荐引用方式(GB/T 7714):
Lu Yi,Xiao Ting,Lai Rongrong,et al.Co-Delivery of Loxoprofen and Tofacitinib by Photothermal Microneedles for Rheumatoid Arthritis Treatment[J].PHARMACEUTICS.2023,15(5):doi:10.3390/pharmaceutics15051500.
APA:
Lu Yi,Xiao Ting,Lai Rongrong,Liu Ziyi,Luo Weixuan...&Xu Yuehong.(2023).Co-Delivery of Loxoprofen and Tofacitinib by Photothermal Microneedles for Rheumatoid Arthritis Treatment.PHARMACEUTICS,15,(5)
MLA:
Lu Yi,et al."Co-Delivery of Loxoprofen and Tofacitinib by Photothermal Microneedles for Rheumatoid Arthritis Treatment".PHARMACEUTICS 15..5(2023)