载姜黄素纳米结构脂质载体增强溃疡性结肠炎的治疗作用。

PURPOSE: Berberine (BBR), a major ingredient extracted from , is a natural drug with limited oral bioavailability. We developed nanostructured lipid carriers (NLCs) as a delivery system for enhanced anti-inflammatory activity of BBR against ulcerative colitis (UC). METHODS: BBR-loaded nanostructured lipid carriers (BBR-NLCs) prepared via high-pressure homogenization were evaluated for particle size, zeta potential, drug entrapment efficiency, drug loading, drug release, toxicity, and cellular uptake. The anti-UC activities of free and encapsulated BBR were evaluated in a DSS-induced acute model of UC in mice. RESULTS: Spherical BBR-NLCs were prepared with a particle size of 63.96± 0.31 nm, a zeta potential of +3.16 ± 0.05 mV, an entrapment efficiency of 101.97±6.34%, and a drug loading of 6.00±0.09%. BBR-NLCs showed excellent biocompatibility in vivo. Cellular uptake experiments showed that BBR-NLCs improved uptake of BBR by RAW 264.7 cells and Caco-2 cells. Oral administration of BBR-NLCs significantly alleviated colitis symptoms (DAI, colon length, spleen swelling, MPO activity) through inhibition of NF-κB nuclear translocation, decreased expression of pro-inflammatory cytokines (IL-1β, IL-6, MMP-9, CX3CR1, COX-2, TERT), and increased expression of the tight junction protein ZO-1. CONCLUSION: BBR-loaded NLCs improved colitis symptoms, which suggested that this may be a novel formulation for treatment of UC.

目的：小檗碱（BBR）是从黄连中提取的主要成分，是一种口服生物利用度有限的天然药物。我们开发了纳米结构脂质载体（NLC）作为一种递送系统，以增强 BBR 对溃疡性结肠炎（UC）的抗炎活性。

方法：通过高压匀质法制备载有 BBR 的纳米结构脂质载体（BBR-NLC），并对其粒径、Zeta 电位、药物包封效率、载药量、药物释放、毒性和细胞摄取进行评价。在 DSS 诱导的 UC 急性模型中，评价游离和包封 BBR 的抗 UC 活性。

结果：制备了粒径为 63.96±0.31nm、Zeta 电位为+3.16±0.05mV、包封效率为 101.97±6.34%、载药量为 6.00±0.09%的球形 BBR-NLC。BBR-NLC 在体内具有良好的生物相容性。细胞摄取实验表明，BBR-NLC 提高了 RAW 264.7 细胞和 Caco-2 细胞对 BBR 的摄取。BBR-NLC 的口服给药通过抑制 NF-κB 核易位、降低促炎细胞因子（IL-1β、IL-6、MMP-9、CX3CR1、COX-2、TERT）的表达和增加紧密连接蛋白 ZO-1 的表达，显著缓解了结肠炎症状（DAI、结肠长度、脾肿大、MPO 活性）。

结论：载有 BBR 的 NLC 改善了结肠炎症状，这表明它可能是治疗 UC 的一种新制剂。