Trotta Valentina, Lee Wing-Hin, Loo Ching-Yee, Haghi Mehra, Young Paul M, Scalia Santo, Traini Daniela
Respiratory Technology, Woolcock Institute of Medical Research, and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia; Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy.
Respiratory Technology, Woolcock Institute of Medical Research, and Discipline of Pharmacology, Sydney Medical School, The University of Sydney, NSW 2006, Australia.
Int J Pharm. 2015 Aug 1;491(1-2):190-7. doi: 10.1016/j.ijpharm.2015.06.033. Epub 2015 Jun 24.
The aim of the study was to prepare inhalable resveratrol by spray drying for the treatment of chronic obstructive pulmonary disease (COPD). Resveratrol, with a spherical morphology and particle diameter less than 5 μm, was successfully manufactured. Fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of spray-dried resveratrol was 39.9 ± 1.1% and 3.7 ± 0.1 μm, respectively, when assessed with an Andersen cascade impactor (ACI) at 60 l/min. The cytotoxicity results of resveratrol on Calu-3 revealed that the cells could tolerate high concentration of resveratrol (up to 160 μM). In addition, in transport experiments using Snapwells, it was observed that more than 80% of the deposited dry powder was transported across the Calu-3 cells to the basal chamber within four hours. The expression of interleukin-8 (IL-8) from Calu-3 induced with tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β1) and lipopolysaccharide (LPS) were significantly reduced after treatment with spray-dried resveratrol. The antioxidant assay (radical scavenging activity and nitric oxide production) showed spray-dried resveratrol to possess an equivalent antioxidant property as compared to vitamin C. Results presented in this investigation suggested that resveratrol could potentially be developed as a dry powder for inhalation for the treatment of inflammatory lung diseases like COPD.
本研究的目的是通过喷雾干燥制备可吸入的白藜芦醇,用于治疗慢性阻塞性肺疾病(COPD)。成功制备出了形态呈球形、粒径小于5μm的白藜芦醇。使用安德森级联撞击器(ACI)在60升/分钟的条件下评估时,喷雾干燥白藜芦醇的细颗粒分数(FPF)和质量中值空气动力学直径(MMAD)分别为39.9±1.1%和3.7±0.1μm。白藜芦醇对Calu-3细胞的细胞毒性结果表明,细胞能够耐受高浓度的白藜芦醇(高达160μM)。此外,在使用跨孔滤器的转运实验中,观察到超过80%的沉积干粉在4小时内穿过Calu-3细胞转运至基底腔室。用喷雾干燥白藜芦醇处理后,肿瘤坏死因子α(TNF-α)、转化生长因子β(TGF-β1)和脂多糖(LPS)诱导的Calu-3细胞中白细胞介素-8(IL-8)的表达显著降低。抗氧化测定(自由基清除活性和一氧化氮生成)表明,喷雾干燥白藜芦醇与维生素C相比具有同等的抗氧化性能。本研究结果表明,白藜芦醇有可能被开发成一种用于吸入治疗COPD等炎症性肺病的干粉。