Laboratory of Pulmonary Research, Department of Pharmaceutical Technology, Centre for Excellence in Nanobio Translational Research (CENTRE), University College of Engineering, Anna University, BIT Campus, Tiruchirappalli 620024, Tamil Nadu, India.
Department of In vivo Toxicology, Diligence Bio Pvt. Ltd., Pondicherry 605502, India.
Int J Pharm. 2020 Dec 15;591:119958. doi: 10.1016/j.ijpharm.2020.119958. Epub 2020 Oct 22.
Vibrating mesh nebulizers are recognized as the most efficient actuation technique over conventional inhalers for drug deposition. This study explored hyaluronic acid (HA) decorated, ferulic acid (FA) loaded chitosan (CS) nanoparticle (FACHA) aerosolized using vibrating mesh nebulizer as strategic combination of drug, nanocarrier and delivery device for effective asthma control. FACHA exhibited spherical morphology with suitable size (164.2 ± 9.7 nm), zeta potential (24.0 ± 0.5 mV), entrapment efficiency (EE%) (65.0 ± 1.5), loading capacity (LC%) (18.5 ± 0.4) and mass median aerodynamic diameter (MMAD) of 1.81 ± 0.15 µm, ascertaining efficient drug deposition. In vivo inhalation toxicity assessment confirmed safety, while, FACHA prophylaxis mitigated inflammation, airway hypersensitivity and remodelling in ovalbumin (OVA) induced mice models. The results thus accentuated the role of pro-pulmonary surface chemistry conferred by HA functionalization that improved 1) thermal stability (thermogravimetric analysis - TGA) and 2) therapeutic efficacy of FA, by facilitating better interaction and transportation across mucus barrier, which otherwise suffers poor bioavailability and rapid metabolism.
振动网孔雾化器被认为是比传统吸入器更有效的药物沉积驱动技术。本研究探索了使用振动网孔雾化器雾化的透明质酸(HA)修饰、阿魏酸(FA)负载壳聚糖(CS)纳米颗粒(FACHA),作为药物、纳米载体和给药装置的战略组合,以有效控制哮喘。FACHA 呈现出合适大小(164.2±9.7nm)、Zeta 电位(24.0±0.5mV)、包封效率(EE%)(65.0±1.5)、载药量(LC%)(18.5±0.4)和质量中值空气动力学直径(MMAD)为 1.81±0.15μm 的球形形态,确保了药物的有效沉积。体内吸入毒性评估证实了其安全性,而 FACHA 预防可减轻卵清蛋白(OVA)诱导的小鼠模型中的炎症、气道高反应性和重塑。因此,结果强调了 HA 功能化赋予的亲肺表面化学性质的作用,这提高了 1)热稳定性(热重分析-TGA)和 2)FA 的治疗效果,通过促进更好的相互作用和穿过粘液屏障的运输,否则 FA 会遭受较差的生物利用度和快速代谢。