Khan Iftikhar, Sabu Maria, Hussein Nozad, Omer Huner, Houacine Chahinez, Khan Wasiq, Elhissi Abdelbary, Yousaf Sakib
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, United Kingdom.
School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, United Kingdom.
J Pharm Sci. 2025 May;114(5):103713. doi: 10.1016/j.xphs.2025.103713. Epub 2025 Feb 27.
Aerosolization is a non-invasive approach of delivering drugs for both localized and systemic effects, specifically pulmonary targeting. The aim of this study was to deliver trans-resveratrol (TR) as an anti-cancer drug entrapped in a new generation versatile carriers nanostructured lipid carrier (NLC) to protect degradation and improve bioavailability via medical nebulizers. Twelve TR-NLC (i.e., F1-F12) formulations were prepared using different combinations and ratios of formulation ingredients via hot high-pressure homogenization. Upon analysis, formulations F1 and F2 demonstrated a particle size of <185 nm, a polydispersity index (PDI) <0.25, Zeta potential values of ∼30 mV and an entrapment efficiency >94%. The aerosolization performance of the F1 and F2 formulations was performed via a next generation impactor (NGI), using medical nebulizers. The air jet nebulizer demonstrated lower drug deposition in the earlier stages (1-2) and significantly higher deposition in the latter stages 3-5 (for both formulations), targeting middle to lower lung deposition. Moreover, the air jet nebulizer exhibited significantly higher emitted dose (ED) (87.44 ± 3.36%), fine particle dose (FPD) (1652.52 ± 9.68 µg) fine particle fraction (FPF) (36.25 ± 4.26%), and respirable fraction (RF) (93.41 ± 4.03%) when the F1 formulation was used as compared to the F2 formulation. Thus, the TR-NLC F1 formulation and air jet nebulizer were identified as the best combination for the delivery and targeting peripheral lungs.
雾化是一种用于实现局部和全身效应（特别是肺部靶向）的非侵入性给药方法。本研究的目的是通过医用雾化器将反式白藜芦醇（TR）作为抗癌药物包裹在新一代多功能载体纳米结构脂质载体（NLC）中，以保护其不被降解并提高生物利用度。通过热高压均质法，使用不同的配方成分组合和比例制备了12种TR-NLC（即F1-F12）制剂。经分析，F1和F2制剂的粒径<185 nm，多分散指数（PDI）<0.25，Zeta电位值约为30 mV，包封率>94%。使用医用雾化器，通过下一代撞击器（NGI）对F1和F2制剂的雾化性能进行了测试。空气喷射雾化器在前几个阶段（1-2）的药物沉积较低，而在后面几个阶段（3-5）的沉积显著较高（两种制剂均如此），靶向中下部肺部沉积。此外，与F2制剂相比，当使用F1制剂时，空气喷射雾化器的发射剂量（ED）（87.44±3.36%）、细颗粒剂量（FPD）（1652.52±9.68μg）、细颗粒分数（FPF）（36.25±4.26%）和可吸入分数（RF）（93.41±4.03%）显著更高。因此，TR-NLC F1制剂和空气喷射雾化器被确定为递送和靶向周边肺部的最佳组合。
