Quadros Mural, Goyal Mimansa, Chauhan Gautam, Gadhave Dnyandev, Gupta Vivek
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Pharmaceutics. 2025 Apr 22;17(5):540. doi: 10.3390/pharmaceutics17050540.
Celastrol (Cela), a phytochemical extracted from , has been extensively investigated for its potential anti-inflammatory, anti-psoriatic, antioxidant, neuroprotective, and antineoplastic properties. However, its clinical translation is limited due to poor bioavailability, low solubility, and nonspecific toxicity. This study aimed to develop and evaluate an inhalable Cela-loaded nanoemulsion (NE) formulation to enhance targeted drug delivery and therapeutic efficacy in non-small cell lung cancer (NSCLC). The NE formulation was optimized using Capmul MCM (25%), Tween 80 (20%), Transcutol HP (5%), and water (50%) as the oil, surfactant, co-surfactant, and aqueous phase, respectively. Physicochemical characterization included globule size, zeta potential, and drug release in simulated lung fluid. In vitro aerosolization performance, cytotoxicity in NSCLC cell lines (A549), scratch and clonogenic assays, and 3D tumor spheroid models were employed to assess therapeutic potential. The NE showed a globule size of 201.4 ± 3.7 nm and a zeta potential of -15.7 ± 0.2 mV. Drug release was sustained, with 20.4 ± 5.5%, 29.1 ± 10%, 64.6 ± 4.1%, and 88.1 ± 5.2% released at 24, 48, 72, and 120 h, respectively. In vitro aerosolization studies indicated a median aerodynamic particle size of 4.8 ± 0.2 μm, confirming its respirability in the lung. Cell culture studies indicated higher toxicity of NE-Cela in NSCLC cells. NE-Cela significantly reduced A549 cell viability, showing a ~6-fold decrease in IC (0.2 ± 0.1 μM) compared to Cela alone (1.2 ± 0.2 μM). Migration and clonogenic assays demonstrated reduced cell proliferation, and 3D spheroid models supported its therapeutic activity in tumor-like environments. The inhalable NE-Cela formulation improved Cela's physicochemical limitations and demonstrated enhanced anti-cancer efficacy in NSCLC models. These findings support its potential as a targeted, well-tolerated therapeutic option for lung cancer treatment.
雷公藤红素（Cela）是一种从[植物名称未给出]中提取的植物化学物质，因其潜在的抗炎、抗银屑病、抗氧化、神经保护和抗肿瘤特性而受到广泛研究。然而，由于其生物利用度低、溶解度低和非特异性毒性，其临床转化受到限制。本研究旨在开发和评估一种可吸入的载雷公藤红素纳米乳剂（NE）制剂，以增强非小细胞肺癌（NSCLC）的靶向药物递送和治疗效果。使用Capmul MCM（25%）、吐温80（20%）、Transcutol HP（5%）和水（50%）分别作为油相、表面活性剂、助表面活性剂和水相，对NE制剂进行了优化。物理化学表征包括球粒大小、zeta电位和在模拟肺液中的药物释放。采用体外雾化性能、NSCLC细胞系（A549）的细胞毒性、划痕和克隆形成试验以及3D肿瘤球体模型来评估治疗潜力。NE的球粒大小为201.4±3.7 nm，zeta电位为-15.7±0.2 mV。药物释放持续，在24、48、72和120小时分别释放20.4±5.5%、29.1±10%、64.6±4.1%和88.1±5.2%。体外雾化研究表明，空气动力学中位粒径为4.8±0.2μm，证实其可在肺部呼吸。细胞培养研究表明，NE-Cela对NSCLC细胞的毒性更高。与单独使用雷公藤红素（1.2±0.2μM）相比，NE-Cela显著降低了A549细胞活力，IC50降低了约6倍（0.2±0.1μM）。迁移和克隆形成试验表明细胞增殖减少，3D球体模型支持其在肿瘤样环境中的治疗活性。可吸入的NE-Cela制剂改善了雷公藤红素的物理化学局限性，并在NSCLC模型中显示出增强的抗癌疗效。这些发现支持了其作为肺癌治疗的靶向、耐受性良好的治疗选择的潜力。
