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Messung der Permeabilitätskoeffizienten bei dem inhalierbaren Antibiotikum Ciprofloxacin HCl Monohydrat

: Sonnenschein, Nico
: Walker, Gottfrid; Hansen, Tanja

Emden-Leer, 2019, 100 S.
Emden-Leer, Hochschule, Master Thesis, 2019
Master Thesis
Fraunhofer ITEM ()
apparent permeability coefficient; Ciprofloxacin HCl monohydrate; Submerse and ALI exposure; Calu-3 cells; AT-1 cells; LC-MS/MS; PBPK; Apical; lining fluid

During this masterthesis the apparent permeability coefficient (Papp) was determined for the inhalable antibiotic Ciprofloxacin HCl monohydrate and the AT-1 and Calu-3 cell lines. These two cell lines consist of immortalized cells derived from the epithelium of the lung, the Calu-3 cells exhibiting a phenotype corresponding to the cells of the small airways, while the AT-1 cells resemble the alveolar epithelial cells of type 1. The epithelium in the alveolar region of the lung forms the blood-air barrier at which the gas exchange takes place. The different Papp values were determined under two different exposure conditions. Both cell lines were each subjected to one submerged exposure and two ALI exposures (air-liquid interface). For the submerged exposure, the antibiotic CHM was dissolved and added into the apical medium prepared for exposure. The cells exposed under ALI conditions were supplied with CHM aerosol processed via the PreciseInhale system in combination with the P.R.I.T.®ExpoCube®. During the ALI exposure there was no liquid on the cells except for the lining fluid produced by the cells themselves. After exposure the samples of the individual experiments were analysed by LC-MS/MS and the Papp was determined. For the cells under submerged conditions, the Papp was determined at AT-1 = 6.34*10-7 cm/sec and Calu-3 = 7.24*10-7 cm/sec. The mean values for the two ALI exposures showed a Papp of 1.99*10-9 cm/sec for AT-1 and a Papp of 1.09*10-8 cm/sec for Calu-3. The Papp values thus determined were afterwards used in the physiologically based pharmacokinetic model (PBPK) to simulate the ADME processes (absorption, distribution, metabolism and excretion) in the human body.