School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, United Kingdom.
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, United Kingdom.
Int J Pharm. 2024 Oct 25;664:124591. doi: 10.1016/j.ijpharm.2024.124591. Epub 2024 Aug 19.
Pulmonary drug delivery via aerosolization is a non-intrusive method for achieving localized and systemic effects. The aim of this study was to establish the impact of viscosity as a novel aspect (i.e., low, medium and high) using various lipid-based formulations (including liposomes (F1-F3), transfersomes (F4-F6), micelles (F7-F9) and nanostructured lipid carriers (NLCs; F10-F12)) as well as to investigate their impact on in-vitro nebulization performance using Trans-resveratrol (TRES) as a model anticancer drug. Based on the physicochemical properties, micelles (F7-F9) elicited the smallest particle size (12-174 nm); additionally, all formulations tested exhibited high entrapment efficiency (>89 %). Through measurement using capillary viscometers, NLC formulations exhibited the highest viscosity (3.35-10.04 m/sec). Upon using a rotational rheometer, formulations exhibited shear-thinning (non-Newtonian) behaviour. Air jet and vibrating mesh nebulizers were subsequently employed to assess nebulization performance using an in-vitro model. Higher viscosity formulations elicited a prolonged nebulization time. The vibrating mesh nebulizer exhibited significantly higher emitted dose (ED), fine particle fraction (FPF) and fine particle dose (FPD) (up to 97 %, 90 % and 64 µg). Moreover, the in-vitro release of TRES was higher at pH 5, demonstrating an alignment of the release profile with the Korsmeyer-Peppas model. Thus, formulations with higher viscosity paired with a vibrating mesh nebulizer were an ideal combination for delivering and targeting peripheral lungs.
通过气溶胶化进行肺部药物输送是实现局部和全身作用的一种非侵入性方法。本研究旨在确定粘度作为一种新的方面（即低、中、高）的影响，使用各种基于脂质的制剂（包括脂质体（F1-F3）、传递体（F4-F6）、胶束（F7-F9）和纳米结构脂质载体（NLCs；F10-F12）），并研究其对使用反式白藜芦醇（TRES）作为模型抗癌药物的体外雾化性能的影响。基于理化性质，胶束（F7-F9）产生的粒径最小（12-174nm）；此外，所有测试的制剂均表现出高包封效率（>89%）。通过使用毛细管粘度计进行测量，NLC 制剂表现出最高的粘度（3.35-10.04m/sec）。使用旋转流变仪，制剂表现出剪切稀化（非牛顿）行为。随后使用空气射流和振动网孔雾化器，使用体外模型评估雾化性能。较高粘度的制剂产生更长的雾化时间。振动网孔雾化器表现出显著更高的发射剂量（ED）、细颗粒分数（FPF）和细颗粒剂量（FPD）（高达 97%、90%和 64μg）。此外，TRES 的体外释放在 pH 5 时更高，表明释放曲线与 Korsmeyer-Peppas 模型一致。因此，与振动网孔雾化器配合使用具有较高粘度的制剂是输送和靶向外周肺的理想组合。
