School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Carbohydr Polym. 2022 Feb 1;277:118819. doi: 10.1016/j.carbpol.2021.118819. Epub 2021 Oct 27.
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-α 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.
银屑病的单药治疗效果不佳，因此需要制定联合策略以实现协同治疗，但这仍然具有挑战性。我们制备了壳聚糖/透明质酸纳米凝胶来共载甲氨蝶呤（MTX）和 5-氨基酮戊酸（ALA），即 MTX-ALA 纳米凝胶，用于银屑病的联合化学-光动力治疗。与 MTX-ALA 混悬液相比，纳米凝胶在体外和体内增强了 MTX 和 ALA 经皮渗透和滞留（p<0.001）。纳米凝胶增强了细胞摄取（p<0.001）、原卟啉 IX 转化（p<0.001）和活性氧的生成（3.93 倍），随后对脂多糖刺激的 HaCaT 细胞发挥协同抗增殖和凋亡作用，凋亡率为 78.6%。MTX-ALA 纳米凝胶可有效改善咪喹莫特诱导的银屑病小鼠的皮肤表现，并下调 TNF-α 和 IL-17A 等促炎细胞因子（p<0.001）。重要的是，MTX-ALA 纳米凝胶降低了口服 MTX 对肝脏和肾脏的毒性。这些结果表明，MTX-ALA 纳米凝胶是一种方便、有效且安全的银屑病联合化学-光动力治疗策略。
