Huck Benedikt, Hidalgo Alberto, Waldow Franziska, Schwudke Dominik, Gaede Karoline I, Feldmann Claus, Carius Patrick, Autilio Chiara, Pérez-Gil Jesus, Schwarzkopf Konrad, Murgia Xabier, Loretz Brigitta, Lehr Claus-Michael
Helmholtz Center for Infection Research, Helmholtz Institute for Pharmaceutical Research Saarland, Department of Drug Delivery Saarland University Campus E8.1 66123 Saarbrucken Germany.
Department of Pharmacy Saarland University Campus E8 1 66123 Saarbrücken Germany.
Small Sci. 2021 Oct 23;1(12):2100067. doi: 10.1002/smsc.202100067. eCollection 2021 Dec.
The interplay of particles with pulmonary surfactant, a lipid-protein material pivotal for lung function, is hypothesized as a key factor that has not been routinely considered in the current in vitro models when determining the fate of inhaled nanomaterials. To explain its influence on cellular uptake and protective effects, nanoparticles are studied on two models of alveolar cells, in the absence or presence of pulmonary surfactant. Composition and interfacial performance of native human and porcine surfactants, a commercially available bovine surfactant (Alveofact), and an artificial lung lining fluid are characterized using shotgun lipidomics and biophysical approaches (i.e., Langmuir surface balances and captive bubble surfactometry). Plain and aminofunctionalized silica nanoparticles and a novel antimycobacterial nanoformulated benzothiazinone (BTZ043) are selected as examples of neutral, positively charged and therapeutically relevant nanoparticles, respectively. They are deposited onto monocultures of human alveolar epithelial and phagocytic cell lines in the presence or absence of the surfactant preparations, modeling the alveolar milieu. Only surfactant preparations with high interfacial activity and distinctive composition mitigated the toxicity of aerosolized particles, along with a tendency of aerosolized particles to aggregate. Key requirements of surfactant preparations needed when studying interactions of nanomaterials with the pulmonary air-blood barrier in vitro are identified.
颗粒与肺表面活性物质（一种对肺功能至关重要的脂质 - 蛋白质物质）之间的相互作用，被认为是当前体外模型在确定吸入纳米材料的归宿时未常规考虑的关键因素。为了解释其对细胞摄取和保护作用的影响，在有或没有肺表面活性物质的情况下，在两种肺泡细胞模型上研究了纳米颗粒。使用鸟枪法脂质组学和生物物理方法（即朗缪尔表面天平法和俘获气泡表面张力测定法）对天然人源和猪源表面活性物质、市售牛源表面活性物质（Alveofact）以及人工肺内衬液的组成和界面性能进行了表征。分别选择普通和氨基功能化二氧化硅纳米颗粒以及一种新型抗分枝杆菌纳米制剂苯并噻嗪酮（BTZ043）作为中性、带正电荷和具有治疗相关性的纳米颗粒的示例。在有或没有表面活性物质制剂的情况下，将它们沉积在人肺泡上皮细胞系和吞噬细胞系的单培养物上，模拟肺泡环境。只有具有高界面活性和独特组成的表面活性物质制剂才能减轻雾化颗粒的毒性，同时雾化颗粒有聚集的趋势。确定了在体外研究纳米材料与肺气血屏障相互作用时所需的表面活性物质制剂的关键要求。
