Abstract:
Hypertrophic 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.
摘要:
增生性瘢痕(HS),这是由于再上皮化伤口的长期炎症和过度纤维化造成的,是最常见的临床挑战之一。因此,制备复杂的透皮转移体纳米凝胶(TA/Fu-TS)以通过协同抑制炎症和抑制纤维化来控制HS形成。TA/Fu-TS具有独特的结构,包括脂质多层中的疏水性曲安奈德(TA)和水性核心中的亲水性5-氟尿嘧啶,并在新出现的HS组织中对巨噬细胞和HS成纤维细胞的经皮共递送方面表现令人满意。根据体外/体内结果,TA/Fu-TS不仅通过白细胞介素相关途径促进巨噬细胞表型转换抑制炎症,但也通过胶原相关途径抑制纤维化重塑细胞外基质。因此,TA/Fu-TS克服了新出现的HS组织中的长期炎症和过度纤维化,并通过巨噬细胞表型转换和抗纤维化作用的协同作用为控制HS形成提供了有效的治疗策略。