Examining the efficacy of localised gemcitabine therapy for the treatment of pancreatic cancer using a hybrid agent-based model
Fig 3
Calibration of model parameters to in vitro experiments.
(A) Drug release profiles for gemcitabine with 3% alginate 15% PCL were measured by placing the gemcitabine–loaded alginate fibre in a solution bath and measuring the released drug concentration over time. (B) The drug concentration in the solution bath (black) was used to fit model parameters for the drug release from the fibre (green). Resulting parameters are in Table A in S1 Text. (C) The drug–induced death rate of pancreatic cancer cells was determined by simplifying the full model assumptions to consider a homogeneous model for live cancer cells PL(t) that were proliferating and dying (become dead cells PD(t)) through the effect of the drug gemcitabine C(t), Eqs (9)–(11). (D) Fitting an exponential growth curve to Mia–PaCa–2 cell proliferation in vitro [91] gave the growth rate of cells ϕ. Values are the mean±std. (E) To measure the efficacy of the protocol, the cell viability was determined after aliquots from drug released from gemcitabine–loaded fibre were placed in a well with proliferating Mia–PaCa–2 cells at 24, 48 and 72 hours. (F) The resulting cell viability at 72 hours from the experiment depicted in (E) was used to fit the drug–induced cell death rate (Eqs (9)–(11)). The data is plotted as a box and whisker plot. Resulting parameters for (D) and (F) are in Table B in S1 Text.