School of Basic Medical Sciences, Xi'an Key Laboratory of Immune Related Diseases, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Int J Nanomedicine. 2022 Feb 9;17:603-616. doi: 10.2147/IJN.S347506. eCollection 2022.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of unknown aetiology affecting the colon and rectum. Pterostilbene (PS) has been reported as an effective antioxidant and anti-inflammatory agent in preclinical IBD models. However, the therapeutic outcomes of PS are limited by potential side effects associated with the systemic exposure and the modest bioavailability afforded by its oral administration. These issues can be improved with the use of intelligent responsive nanoparticles with the ability of lysosome escape, given their high drug delivery capacity and reducing the side effects.
Herein, the hyaluronic acid (HA)-modified L-arginine CO nanoparticles (HA-L-Arg-CO@NPs) loaded with PS (HA-PS@NPs) are constructed. Under lysosomal pH conditions, HA-PS@NPs liberate CO and generate a pH-activated nano-bomb effect to augment the cytosolic delivery of PS.
HA-L-Arg-CO@NPs show great biocompatibility and the excellent ability to target the colon. Using lipopolysaccharide-induced inflammation in vitro, the prominent anti-inflammatory effect of HA-L-Arg-CO@NPs and HA-PS@NPs is observed. Further, orally administered HA-L-Arg-CO@NPs and HA-PS@NPs via the colon-targeted chitosan/alginate (CA) hydrogel downregulate pro-inflammatory cytokines and reduce intestinal permeability, yielding significant outcomes in alleviating the symptoms of UC.
This pH-activated "nano-bomb" carrier with therapeutic effect can be exploited as efficient oral drug carriers for UC treatment.
溃疡性结肠炎（UC）是一种病因不明的慢性炎症性肠病（IBD），影响结肠和直肠。研究表明，白藜芦醇（PS）在临床前 IBD 模型中是一种有效的抗氧化和抗炎剂。然而，PS 的治疗效果受到其全身暴露相关的潜在副作用和口服给药时适度的生物利用度的限制。这些问题可以通过使用具有溶酶体逃逸能力的智能响应纳米粒子来改善，因为它们具有高药物递送能力并减少副作用。
本文构建了透明质酸（HA）修饰的 L-精氨酸 CO 纳米粒子（HA-L-Arg-CO@NPs）负载 PS（HA-PS@NPs）。在溶酶体 pH 条件下，HA-PS@NPs 释放 CO 并产生 pH 激活的纳米炸弹效应，增强 PS 的细胞内递送。
HA-L-Arg-CO@NPs 表现出良好的生物相容性和靶向结肠的优异能力。通过体外脂多糖诱导的炎症，观察到 HA-L-Arg-CO@NPs 和 HA-PS@NPs 的显著抗炎作用。此外，通过结肠靶向壳聚糖/海藻酸钠（CA）水凝胶口服给予 HA-L-Arg-CO@NPs 和 HA-PS@NPs，下调促炎细胞因子并降低肠道通透性，对缓解 UC 症状有显著效果。
这种具有治疗作用的 pH 激活“纳米炸弹”载体可用作治疗 UC 的有效口服药物载体。
