Chitosan/hyaluronan nanogels co-delivering methotrexate and 5-aminole-vulinic acid: A combined chemo-photodynamic therapy for psoriasis
Chitosan/hyaluronan nanogels co-delivering methotrexate and 5-aminole-vulinic acid: A combined chemo-photodynamic therapy for psoriasis
复制标题
DOI：
10.1016/j.carbpol.2021.118819
复制
发表时间：
2021-10-29
影响因子：
11.2
通讯作者：
Xu, Yuehong
中科院分区：
文献类型：
--
作者：
Wang, Yixuan;Fu, Shijia;Xu, Yuehong
银屑病对单药治疗没有充分的反应，定制协同治疗的联合策略仍然具有挑战性。我们制备了壳聚糖/透明质酸纳米凝胶以共负载甲氨蝶呤（MTX）和5-氨基乙酰丙酸（ALA），即，MTX-ALA NG，用于银屑病的联合化学-光动力疗法。与MTX-ALA混悬液相比，NG在体外和体内均能促进MTX和ALA的透皮吸收和滞留（p < 0.001）。NGs可增强细胞摄取（p < 0.001）、原卟啉IX转化（p < 0.001）和活性氧生成（p <0.001），对脂多糖刺激的HaCaT细胞具有协同抗增殖和凋亡作用，凋亡率为78.6%。MTX-ALA NG有效地改善了咪喹莫特诱导的银屑病小鼠的皮肤表现并下调了TNF-α和IL-17 A的促炎细胞因子（p < 0.001）。重要的是，MTX-ALA NG降低了口服MTX对肝脏和肾脏的毒性。结果支持MTX-ALA NG是一种方便、有效、安全的联合化学-光动力学策略治疗银屑病。
Psoriasis does not respond adequately to the monotherapy, tailoring combined strategies for synergistical treatment remains challenging. We fabricated chitosan/hyaluronan nanogels to co-load methotrexate (MTX) and 5-aminoleavulinic acid (ALA), i.e., MTX-ALA NGs, for a combined chemo-photodynamic therapy for psoriasis. Compared with MTX-ALA suspension, the NGs enhanced the penetration and retention of MTX and ALA through and into the skin in vitro and in vivo (p < 0.001). NGs enhanced the cellular uptake (p < 0.001), protoporphyrin IX conversion (p < 0.001), and reactive oxygen species generation (3.93-fold), subsequently exerted the synergistical anti-proliferation and apoptosis on lipopolysaccharide-irritated HaCaT cells with the apoptosis rate of 78.6%. MTX-ALA NGs efficiently ameliorated the skin manifestations and down-regulated the proinflammatory cytokines of TNF-alpha and IL-17A in imiquimod-induced psoriatic mice (p < 0.001). Importantly, MTX-ALA NGs reduced the toxicities of oral MTX to the liver and kidney. The results support that MTX-ALA NG is a convenient, effective, and safe combined chemo-photodynamic strategy for psoriasis treatment.