Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510000, People's Republic of China.
Guangzhou (Jinan) Biomedical Research and Development Center, Guangzhou 510000, People's Republic of China.
Int J Nanomedicine. 2020 Jun 3;15:3937-3951. doi: 10.2147/IJN.S247406. eCollection 2020.
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).
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.
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.
BBR-loaded NLCs improved colitis symptoms, which suggested that this may be a novel formulation for treatment of UC.
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。
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。
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）。
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。
