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Pharmacokinetics and Pharmacodynamics of Drugs Delivered to the Lung
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Stefanie K. Drescher, Mong-Jen Chen, Jürgen B. Bulitta, Günther Hochhaus
The Calu-3 (American type culture collection ATCC HTB-55) derived from an adenocarcinoma in a 25-year-old male Caucasian has been applied and evaluated for drug absorption, metabolism, and transport (Ehrhardt and Kim 2008; Steimer et al. 2005). Calu-3 is the only human lung cancer derived cell line that exhibits similar mRNA and protein expression to the native epithelium (Steimer et al. 2005). Another bronchial epithelial cell line, 16HBE14o, was developed by transforming normal bronchial epithelium (of 1st bifurcation) from a 1-year-old male heart-lung transplant patient (Ehrhardt and Kim 2008; Steimer et al. 2005). The lung cells were infected with a SV40 large T-antigen containing a replication defective pSVori-plasmid (Ehrhardt and Kim 2008; Steimer et al. 2005). The 16HBE14o cells have been utilized as a model to examine transport and particle cell interactions, however, these cells are not commercially available (Ehrhardt and Kim 2008).
Bioavailability of inhaled compounds
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
The permeability of inhaled drugs has been studied in cell cultures using different cell lines, including the human bronchial cell lines 16HBE14o-, Calu-3 and BEAS-2B; alveolar cell lines L-2, A549, H441, MLE-15; and alveolar epithelial cells in primary culture (57). The Calu-3 and 16HBE14o- cell lines are most often used because they are readily available and well characterized, and they express features of the airway epithelium and several transport and metabolic systems relevant to drug absorption (58). Among the first published studies, Mathias et al. determined that the permeability of compounds was directly correlated to their lipophilicity and inversely correlated to their molecular weight (MW) (59). Their observations in the Calu-3 cell line correlated well with those in primary cultured rabbit tracheal epithelial cells and with the absorption of these compounds in vivo, after pulmonary administration to rats. The correlation of lipophilicity and permeability was also observed by Forbes et al. in the 16HBE14o- cell line, but the permeability of this cell line to hydrophilic compounds was significantly greater than that observed in alveolar cell cultures, which may be due to the lower resistance reported for the 16HBE14o- cell line (60). These early studies were performed with relatively small MW compounds, but the growing interest in developing a formulation for inhaled insulin fueled the evaluation of the permeability of protein/peptide compounds.
Pulmonary delivery of favipiravir inhalation solution for COVID-19 treatment: in vitro characterization, stability, in vitro cytotoxicity, and antiviral activity using real time cell analysis
Published in Drug Delivery, 2022
Ayca Yildiz Pekoz, Ozlem Akbal Dagistan, Hanan Fael, Meltem Culha, Aybige Erturk, Nur Sena Basarir, Gokben Sahin, Muge Serhatli, Gamze Cakirca, Saban Tekin, Leyla Semiha Sen, Mustafa Sevim, Lutfiye Mulazimoglu Durmusoglu, Berrak C. Yegen
Calu-3 cells were obtained from ATCC (ATCC® HTB-55™; p no. 30-36 used) and cultured in DMEM (p no. 41965 Gibco) supplemented with 5% fetal bovine serum (FBS, Sigma p no. 7524) and 1% antibiotic–antimycotic solution (Sigma, p no. A5955) in the cell culture flasks and incubated at 37 °C and 5% CO2. Calu-3 cells were seeded at a density of 1 × 104 cells/well in the 96-well plates and incubated at 37 °C and 5% CO2 for 24 h. Afterward, cells were treated with different concentration of favipiravir (1, 5 10, 25, and 50 µg mL−1). Following 24-h of incubation, 30 µL of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (Sigma, p no. M5655) solution (5 mg mL−1 in PBS) was added to each well, then the plates were incubated at 37 °C for 4 h. At the end of the incubation period, formazan crystals were dissolved by adding 100 µL of DMSO (Sigma, p no. D8418) into each well. The optical density was measured at 570 nm wavelength with BioTek Microplate reader (ELX50, Vermont, USA).
Evaluation of Calu-3 cell lines as an in vitro model to study the inhalation toxicity of flavoring extracts
Published in Toxicology Mechanisms and Methods, 2022
Xiaoli Ji, Yunhua Sheng, Ying Guan, Yinxia Li, Yuqiong Xu, Liming Tang
In summary, several in vitro models have been developed to study the potential toxicity of inhaled materials, and only a few studies have been performed on the Calu-3 cell line, which is representative of the bronchial epithelial barrier. Much remains to be elucidated concerning the function, structure, and toxicity responses of airway epithelia. This study suggests that culturing Calu-3 cells under ALI conditions and culture times of 8–10 days, cell morphology, and barrier function were optimized in an in vitro model. Under these conditions, cells can be successfully cultured with good cell culture growth and differentiation. Therefore, the Calu-3 cell line has considerable potential as an in vitro model for bronchial epithelium. In vitro evidence concerning the respiratory toxicity caused by e-cigarette-induced flavoring chemicals is scarce, and a reliable in vitro model is required to evaluate their inhalation toxicity.
Odorranalectin modified PEG–PLGA/PEG–PBLG curcumin-loaded nanoparticle for intranasal administration
Published in Drug Development and Industrial Pharmacy, 2020
Xinrui Li, Jing Su, Zul Kamal, Pengcheng Guo, Xinyi Wu, Lina Lu, Hongbing Wu, Mingfeng Qiu
Calu-3 cells were chosen as the cell model. They are directly derived from human airway epithelial cells, which can form a tightly connected monolayer membrane and differentiate into cilia after cultivation. Calu-3 cells express P-glycoprotein, hydrolase and cytochrome. At the same time, Calu-3 cells can simulate properties of the nasal mucosa by secreting mucus [40–43]. Most importantly, Calu-3 cells expressing N-acetylglucosamine can simulate absorption and uptake of NPs by nasal mucosa cells, which simulates properties of the nasal mucosa. Pictures of Calu-3 cells uptake recorded by confocal laser scanning microscope (CLSM) are shown in Figure 9. Fluorescence intensity of Cur solution group was weak. NPs of the same concentration showed strong fluorescence intensity. The OL–NPs group had stronger fluorescence intensity than unmodified NPs group and fluorescence intensity was increased gradually with the reaction time prolonging. Patches of green fluorescence of OL–NPs group could be observed after 4 h, which indicated that Calu-3 cells uptake effect enhanced and reached peak point at 4 h.