Transdermal Transfersome Nanogels Control Hypertrophic Scar Formation via Synergy of Macrophage Phenotype‐Switching and Anti‐Fibrosis Effect

Abstract

AbstractHypertrophic scar (HS), which results from prolonged inflammation and excessive fibrosis in re‐epithelialized wounds, is one of the most common clinical challenges. Consequently, sophisticated transdermal transfersome nanogels (TA/Fu‐TS) are prepared to control HS formation by synergistically inhibiting inflammation and suppressing fibrosis. TA/Fu‐TSs have unique structures comprising hydrophobic triamcinolone acetonide (TA) in lipid multilayers and hydrophilic 5‐fluorouracil in aqueous cores, and perform satisfactorily with regard to transdermal co‐delivery to macrophages and HS fibroblasts in emerging HS tissues. According to the in vitro/vivo results, TA/Fu‐TSs not only promote macrophage phenotype‐switching to inhibit inflammation by interleukin‐related pathways, but also suppress fibrosis to remodel extracellular matrix by collagen‐related pathways. Therefore, TA/Fu‐TSs overcome prolonged inflammation and excessive fibrosis in emerging HS tissues, and provide an effective therapeutic strategy for controlling HS formation via their synergy of macrophage phenotype‐switching and anti‐fibrosis effect.