直接给药发炎的肠道部位治疗溃疡性结肠炎(UC),带来了诸如保留时间之类的重大挑战,吸收变异性,副作用,药物稳定性,和非特定的交付。治疗结肠炎的最新进展旨在改善局部药物的可用性,即炎症部位的灌肠治疗。从而减少全身不良反应。然而,一个关键的限制在于灌肠剂由于快速蠕动而无法在结肠中维持药物,腹泻,和当地依从性差。因此,在这项工作中,我们开发了位点特异性巯基化粘膜粘附阴离子纳米脂质体,以克服常规灌肠治疗的局限性.硫醇化的递送系统允许递送系统在结肠中的发炎部位的延长驻留。通过使用体外和体内模型的巯基化纳米脂质体的粘附潜力证实。为了进一步提供治疗功效,用没食子酸(GA)装载巯基化纳米脂质体,一种以抗菌而闻名的天然化合物,抗氧化剂,和有效的抗炎特性。因此,没食子酸负载的巯基化2,6DALPDMPG(GATh@APDL)证明了靶向粘附到发炎的结肠的潜力,它们的小尺寸100nm和阴离子性质促进。治疗研究表明,该制剂通过减轻结肠炎症提供保护作用,下调NF-κB的表达,HIF-1α,和MMP-9,并显示出优于游离GA灌肠剂的疗效。封装的GA抑制NF-κB表达,导致MUC2蛋白表达增强,从而促进结肠粘膜愈合。此外,GATh@APDL有效减少中性粒细胞浸润并调节结肠固有层中的免疫细胞定量。我们的发现表明GATh@APDL有望缓解UC并解决常规灌肠治疗的局限性。
Directly administering medication to inflamed intestinal sites for treating ulcerative colitis (UC), poses significant challenges like retention time, absorption variability, side effects, drug stability, and non-specific delivery. Recent advancements in therapy to treat colitis aim to improve local drug availability that is enema therapy at the site of inflammation, thereby reducing systemic adverse effects. Nevertheless, a key limitation lies in enemas\' inability to sustain medication in the colon due to rapid peristaltic movement, diarrhea, and poor local adherence. Therefore, in this work, we have developed site-specific thiolated mucoadhesive anionic nanoliposomes to overcome the limitations of conventional enema therapy. The thiolated delivery system allows prolonged residence of the delivery system at the inflamed site in the colon, confirmed by the adhesion potential of thiolated nanoliposomes using in-vitro and in-vivo models. To further provide therapeutic efficacy thiolated nanoliposomes were loaded with gallic acid (GA), a natural compound known for its antibacterial, antioxidant, and potent anti-inflammatory properties. Consequently, Gallic Acid-loaded Thiolated 2,6 DALP DMPG (GATh@APDL) demonstrates the potential for targeted adhesion to the inflamed colon, facilitated by their small size 100 nm and anionic nature. Therapeutic studies indicate that this formulation offers protective effects by mitigating colonic inflammation, downregulating the expression of NF-κB, HIF-1α, and MMP-9, and demonstrating superior efficacy compared to the free GA enema. The encapsulated GA inhibits the NF-κB expression, leading to enhanced expression of MUC2 protein, thereby promoting mucosal healing in the colon. Furthermore, GATh@APDL effectively reduces neutrophil infiltration and regulates immune cell quantification in colonic lamina propria. Our findings suggest that GATh@APDL holds promise for alleviating UC and addressing the limitations of conventional enema therapy.