Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Lidocaine Adsorption Tests
2.3. Cell Isolation and Culture
2.3.1. Adhesion Culture
2.3.2. Three-Dimensional Bioreactor Culture
2.4. Kinetic Tests
2.5. Analytical Methods
2.6. Data Analysis
3. Results
3.1. Lidocaine Adsorption in Cell-Free Bioreactors
3.2. Lidocaine Disappearance in Cell-Seeded Bioreactors
3.2.1. Adhesion Culture
3.2.2. Three-Dimensional Bioreactor Culture
4. Discussion and Conclusions
4.1. Lidocaine Adsorption
4.2. Lidocaine Metabolic Elimination
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Nomenclature
C | solute concentration, M |
Ccell | cell density, cell/cm2 |
CL,a | lidocaine concentration in the adsorbed phase, moles/cm2 |
CO2,eq | dissolved oxygen concentration in medium equilibrating the above gas, M |
Damkoehler number, | |
DO2 | oxygen diffusion coefficient in medium, cm2/s |
fu | unbound lidocaine fraction, |
h | medium thickness above cell surface in adhesion culture, cm |
ki | kinetic constant for the i-th transformation, s−1 |
ki’ = ki/Ccell | cell-specific kinetic constant for the i-th transformation, cm3/(s ncell) |
KM | Michaelis constant, M |
m | number of experiments, |
n | number of data points, |
p | number of model parameters, |
-r | metabolite disappearance rate, M/s |
Subscripts/Superscripts | |
a | adsorption |
d | desorption |
exp | experimental |
i | i-th metabolite |
j | j-th data point |
k | k-th experiment |
mod | model-predicted |
os | species other than MEGX produced by lidocaine metabolic transformation |
A | adhesion culture |
B | bioreactor culture |
L | lidocaine |
M | MEGX |
O2 | dissolved oxygen |
0 | initial value |
1 | lidocaine metabolic transformation |
2 | MEGX further metabolic transformation |
α | reaction rate order |
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Catapano, G.; Unger, J.K.; Zanetti, E.M.; Fragomeni, G.; Gerlach, J.C. Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors. Bioengineering 2021, 8, 104. https://doi.org/10.3390/bioengineering8080104
Catapano G, Unger JK, Zanetti EM, Fragomeni G, Gerlach JC. Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors. Bioengineering. 2021; 8(8):104. https://doi.org/10.3390/bioengineering8080104
Chicago/Turabian StyleCatapano, Gerardo, Juliane K. Unger, Elisabetta M. Zanetti, Gionata Fragomeni, and Jörg C. Gerlach. 2021. "Kinetic Analysis of Lidocaine Elimination by Pig Liver Cells Cultured in 3D Multi-Compartment Hollow Fiber Membrane Network Perfusion Bioreactors" Bioengineering 8, no. 8: 104. https://doi.org/10.3390/bioengineering8080104