In Vitro Pulmonary Cell Culture in Pharmaceutical Inhalation Aerosol Delivery: 2-D, 3-D, and In Situ Bioimpactor Models

Abstract

The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work.

Inhalable Nanoparticles/Microparticles of an AMPK and Nrf2 Activator for Targeted Pulmonary Drug Delivery as Dry Powder Inhalers

“…The effects of SD metformin formulations on the viability of human representative pulmonary cell lines exposed to different concentrations were tested, using similar conditions previously reported ( 42 , 47 ). A549 (a human alveolar epithelial lung adenocarcinoma cell line) and H358 (a bronchioalveolar carcinoma pulmonary cell line) were used as models of the alveolar type I alveolar epithelial cells and alveolar type II cells which express lung surfactant-associated protein A (SP-A), respectively ( 48 ). These cell lines were grown in a growth medium including Dulbecco’s modified Eagle’s medium (DMEM), Advanced 1x, 10% (v/v) fetal bovine serum (FBS), Pen-Strep (100 U/mL penicillin, 100 μg/mL), Fungizone (0.5 μg/mL amphotericin B, 0.41 μg/mL sodium deoxycholate), and 2 mM l -glutamine in a humidified incubator at 37°C and 5% CO 2 .…”

“…After the TEER values reached 500 Ω cm 2 , indicating a confluent monolayer at the ALI, the cells were exposed to 1000 μM of representative SD formulations dissolved in non-supplemented EMEM media. The liquid aerosol formulations were delivered to the Calu-3 cells at the ALI using a Penn-Century MicroSprayer® Aerosolizer Model IA-1B (Philadelphia, PA, USA) ( 42 , 48 ). TEER values were then recorded after 3 h of exposure and then every 24 h up to 7 days after drug exposure, as previously reported ( 42 , 47 ) using an EndOhm 12 mm Culture Cup (World Precision Instruments, Sarasota, FL, USA).…”

Invited review: human air-liquid-interface organotypic airway tissue models derived from primary tracheobronchial epithelial cells—overview and perspectives

“…Ninety percent of small molecular weight (150–200 Da) hydrophobic drugs are rapidly absorbed by passive diffusion (Patton et al 2004 ). In vitro ALI airway models have been employed for assessing the deposition and absorption of inhalable drugs across the epithelium as well as for distinguishing between passive diffusion and active transport (Reus et al 2014 ; Acosta et al 2016 ). Lin and colleagues reported that the transepithelial permeability of a panel of anti-allergy drugs, including fexofenadine-HCl, albuterol, albuterol sulfate, dexamethasone, budesonide, and triamcinolone acetonide, was linearly correlated with their lipophilicity (Lin et al 2007 ).…”

“…Summary of applications using primary cell-based ALI airway tissue modelsAcosta et al 2016;Reus et al 2014 Studying active and passive drug transportLin et al 2007;Madlova et al 2009 Evaluate efficacy of antiviral and antibiotic drug candidatesBrockman-Schneider et al 2014;Mata et al 2012;Outlaw et al 2019;Palermo et al 2009;Tanabe et al 2011; Triana-Baltzer et al 2010;Zimmermann et al 2009Matrosovich et al 2004Zhang et al 2005a;Jakiela et al 2008;Zhang et al 2002;Dijkman et al 2009;Kindler et al 2013; Zhu et al 2020; Pyrc et al Powell et al 2015;Gasperini et al 2017;Guevara et al 2016;Raffel et al 2013;Schwab et al 2002; Balder et al 2009;Prince et al 2018;Reuschl et al 2017;Matsuyama et al 2018;Zhang et al 2005b;Zulianello et al 2006;Soong et al 2011;Verkaik et al 2014 …”

Design and development of innovative microparticulate/nanoparticulate inhalable dry powders of a novel synthetic trifluorinated chalcone derivative and Nrf2 agonist

“…In vitro transepithelial electrical resistance analysis in air-interface culture (AIC). Calu-3 human lung adenocarcinoma cell line derived from the bronchial submucosal airway region was grown in Eagle's minimum essential medium (EMEM), 10% (v/v) fetal bovine serum (FBS), Pen-Strep (100 U/mL penicillin, 100 µg/mL), Fungizone (0.5 µg/mL amphotericin B, 0.41 µg/mL sodium deoxycholate) as previously reported [54][55][56] . They were seeded www.nature.com/scientificreports/ at a concentration of 500,000 cells/mL in Costar Transwells ® (0.4 μm polyester membrane, 12 mm for a 12-well plate).…”