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• W4295272911 abstract "Dissolving microneedles, the promising vehicles for transdermal delivery, are incapable of directly loading hydrophobic components that limit the application of transdermal drug delivery. Microemulsion holds great potential in the solubilisation of water-insoluble drugs but is limited by the high epidermal retention. In this study, we fabricated microemulsion-incorporated dissolving microneedles co-loading celecoxib and α-linolenic acid (Cel-MEs@MNs) for enhancing osteoarthritis (OA) therapy via synergistic anti-inflammation and potent transdermal delivery. Cel-MEs@MNs composed of celecoxib & α-linolenic acid-coloaded microemulsion (Cel-MEs) and hyaluronic acid-based microneedles (MNs) can be completely dissolved in 90 s with a particle size of ∼30 nm. Each microneedle array with a hardness exceeding 30 N contained 57.9 ± 2.5 μg of celecoxib and 442.5 ± 24.2 μg of α-linolenic acid. The 8 h-cumulative transdermal of celecoxib from Cel-MEs@MNs was 89.2 ± 5.1 μg celecoxib/cm2, which is 2.98-fold higher than that from Cel-MEs. Combinational celecoxib and α-linolenic acid with a weight ratio of 1/5 can synergistically induce M1-like macrophage to M2 repolarization, reduce M1-like macrophages-resulted chondrocytes apoptosis, and lower serum prostaglandin E-2 (PGE-2). Notably, Cel-MEs@MNs amplified such collaborated anti-inflammatory effects. More importantly, in the treatment of OA-bearing rat models, Cel-MEs@MNs with a half-dose of celecoxib and α-linolenic acid significantly shrunk the paw swelling, reduced inflammatory cytokines, and improved cartilage damage compared with the oral administration of celecoxib and α-linolenic acid, as well as transdermal administration of Cel-MEs. Such an integrational strategy of microemulsion-incorporated dissolving MNs offers the feasibility of combinational celecoxib and α-linolenic acid in transdermal permeation and boosted OA therapy." @default.
• W4295272911 created "2022-09-12" @default.
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• W4295272911 date "2022-09-18" @default.
• W4295272911 modified "2023-09-29" @default.
• W4295272911 title "Transdermal delivery of celecoxib and α-linolenic acid from microemulsion-incorporated dissolving microneedles for enhanced osteoarthritis therapy" @default.
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• W4295272911 doi "https://doi.org/10.1080/1061186x.2022.2123492" @default.
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