Sudduth Emma R, Kolewe Emily L, Graf Jodi, Yu Yinkui, Somma Joaquina, Fromen Catherine A
Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, DE, USA.
Front Chem Eng. 2023;4. doi: 10.3389/fceng.2022.1086031. Epub 2023 Jan 11.
Nanoparticle evaluation within the pulmonary airspace has increasingly important implications for human health, with growing interest from drug delivery, environmental, and toxicology fields. While there have been widespread investigations of nanoparticle physiochemical properties following many routes of administration, nanoparticle behavior at the air-liquid interface (ALI) is less well-characterized. In this work, we fabricate two formulations of poly(ethylene)-glycol diacrylate (PEGDA)-based model nanoparticles to establish an workflow allowing evaluation of nanoparticle charge effects at the ALI. Both cationic and anionic PEGDA formulations were synthesized with similar hydrodynamic diameters around ~225 nm and low polydispersity, with expected surface charges corresponding with the respective functional co-monomer. We find that both formulations are readily nebulized from an aqueous suspension in a commercial Aeroneb Lab Nebulizer, but the aqueous delivery solution served to slightly increase the overall hydrodynamic and geometric size of the cationic particle formulation. However, nanoparticle loading at 50 μg/ml of either formulation did not influence the resultant aerosol diameter from the nebulizer. To assess aerosol delivery , we designed a 3D printed adapter capable of ensuring aerosol delivery to transwell 24-well culture plates. Nanoparticle uptake by macrophages was compared between traditional cell culture techniques and that of ALI-cultured macrophages following aerosol delivery. Cell viability was unaffected by nanoparticle delivery using either method. However, only traditional cell culture methods demonstrated significant uptake that was dependent on the nanoparticle surface charge. Concurrently, ALI culture resulted in lower metabolic activity of macrophages than those in traditional cell culture, leading to lower overall nanoparticle uptake at ALI. Overall, this work demonstrates that base-material similarities between both particle formulations provide an expected consistency in aerosol delivery regardless of the nanoparticle surface charge and provides an important workflow that enables a holistic evaluation of aerosolizable nanoparticles.
肺部空域内的纳米颗粒评估对人类健康的影响日益重要，药物递送、环境和毒理学领域对其的兴趣也与日俱增。虽然在多种给药途径后对纳米颗粒的物理化学性质进行了广泛研究，但纳米颗粒在气液界面（ALI）的行为特征尚不明确。在这项工作中，我们制备了两种基于聚（乙二醇）二丙烯酸酯（PEGDA）的模型纳米颗粒制剂，以建立一种工作流程，用于评估纳米颗粒在ALI处的电荷效应。阳离子和阴离子PEGDA制剂的合成具有相似的流体动力学直径，约为225 nm，且多分散性低，其预期表面电荷与各自的功能性共聚单体相对应。我们发现，两种制剂都能很容易地从商用Aeroneb Lab雾化器中的水悬浮液中雾化出来，但水性递送溶液略微增加了阳离子颗粒制剂的整体流体动力学和几何尺寸。然而，两种制剂在50 μg/ml的纳米颗粒负载量下，均不影响雾化器产生的气溶胶直径。为了评估气溶胶递送情况，我们设计了一种3D打印适配器，能够确保将气溶胶递送至Transwell 24孔培养板。比较了传统细胞培养技术和气溶胶递送后ALI培养的巨噬细胞对纳米颗粒的摄取情况。使用这两种方法进行纳米颗粒递送均未影响细胞活力。然而，只有传统细胞培养方法显示出显著的摄取，且摄取量取决于纳米颗粒的表面电荷。同时，ALI培养导致巨噬细胞的代谢活性低于传统细胞培养中的巨噬细胞，从而导致ALI处纳米颗粒的总体摄取量较低。总体而言，这项工作表明，两种颗粒制剂之间的基础材料相似性，无论纳米颗粒表面电荷如何，都能在气溶胶递送中提供预期的一致性，并提供了一个重要的工作流程，能够对可雾化纳米颗粒进行全面评估。
