Singh Prashant Anilkumar, Awasthi Rajendra, Pandey Ramendra Pati, Kar Santosh K
Department of Allied Sciences, School of Health Sciences and Technology, UPES, Dehradun-248 007, Uttarakhand, India.
Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Dehradun-248 007, Uttarakhand, India.
ADMET DMPK. 2025 Mar 20;13(2):2661. doi: 10.5599/admet.2661. eCollection 2025.
Curcumin, a polyphenolic bioactive molecule, exhibits potent anti-inflammatory and antioxidant properties by reducing cytokine levels such as IL-6, TNF-α, and TGF-β. It regulates IL-17A and modulates key signaling pathways, including PI3K/AKT/mTOR, NF-κB and JAK/STAT. However, its clinical application is hindered by rapid metabolism, poor solubility, and chemical instability.
Using the Box-Behnken design, this study developed and optimized a curcumin-loaded turmeric oil-based nanoemulsion system. The effects of turmeric oil, Tween 80 and sonication cycles on particle size (PS), polydispersity index (PDI), and encapsulation efficiency were analyzed. The optimized nanoemulsion was characterized by zeta potential, PDI, PS, morphology, loading efficiency, EE, and antioxidant activity (DPPH assay). cytotoxicity was evaluated using A549 cells, while efficacy was assessed in BALB/c mice through histological analysis, bronchoalveolar lavage fluid analysis, and TNF-α and IL-1β estimation via enzyme-linked immunosorbent assay.
The optimized nanoemulsion had high entrapment efficiency (92.45±2.4 %), a PS of 130.6 nm, a PDI of 0.151, and a zeta potential of -1.7±0.6 mV. Nanoparticle tracking analysis confirmed a mean PS of 138.3±1.6 nm with a concentration of 3.78×10 particles/mL. Transmission electron microscopy imaging confirmed spherical morphology. The value was 25.65 μg/mL. The nanoemulsion remained stable for three months at 4±1 and 25±2 °C/ 60±5 % relative humidity. The optimized formulation significantly reduced BALF total cell count, alveolar wall thickening, and TNF-α and IL-1β levels ( < 0.001).
Overall, the optimized formulation significantly lowered levels of pro-inflammatory cytokines in the acute lung injury /acute respiratory distress syndrome mouse model.
姜黄素是一种多酚类生物活性分子，通过降低白细胞介素-6、肿瘤坏死因子-α和转化生长因子-β等细胞因子水平，展现出强大的抗炎和抗氧化特性。它调节白细胞介素-17A并调控关键信号通路，包括磷脂酰肌醇-3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白、核因子-κB和Janus激酶/信号转导子和转录激活子。然而，其快速代谢、低溶解度和化学不稳定性阻碍了它的临床应用。
本研究采用Box-Behnken设计，开发并优化了一种基于姜黄精油的载姜黄素纳米乳剂系统。分析了姜黄精油、吐温80和超声循环对粒径、多分散指数和包封率的影响。通过zeta电位、多分散指数、粒径、形态、负载效率、包封率和抗氧化活性（二苯基苦味酰基自由基测定法）对优化后的纳米乳剂进行表征。使用A549细胞评估细胞毒性，同时通过组织学分析、支气管肺泡灌洗流体分析以及通过酶联免疫吸附测定法测定肿瘤坏死因子-α和白细胞介素-1β，在BALB/c小鼠中评估疗效。
优化后的纳米乳剂具有高包封率（92.45±2.4%），粒径为130.6纳米，多分散指数为0.151，zeta电位为-1.7±0.6毫伏。纳米颗粒跟踪分析证实平均粒径为138.3±1.6纳米，浓度为3.78×10个颗粒/毫升。透射电子显微镜成像证实为球形形态。该值为25.65微克/毫升。纳米乳剂在4±1和25±2°C/60±5%相对湿度下可稳定保存三个月。优化后的制剂显著降低了支气管肺泡灌洗流体总细胞计数、肺泡壁增厚以及肿瘤坏死因子-α和白细胞介素-1β水平（P<0.001）。
总体而言，优化后的制剂在急性肺损伤/急性呼吸窘迫综合征小鼠模型中显著降低了促炎细胞因子水平。
