Stochastic models for prodrug targeting. 1. Diffusion of the efflux drug

In modeling prodrug targeting using the stochastic approach, we first modeled diffusion of the efflux drug. Drug efflux is one of the major reasons for the failure of prodrug strategy: the active agent is pumped out the membrane ("efflux"), causing an insufficient amount to be delivered to the targeted sites and thus diminishing the efficacy of chemotherapy. Because the biological body is a nonlinear nonequilibrium complex system, the molecular transport taking place in vivo often showed stochasticity. The model described here for diffusion of the efflux drug is basically a diffusion process with reflecting/absorbing boundary conditions, divided into two distinctive regions with one allowing the particles to jump to the origin as a result of efflux pumping. We study discrete time birth-death Markov chain and compute the time-dependent spatial probability density function (PDF) of particles. The results showed that the jumping probability, although small, has a significant impact on the evolution of PDF of the efflux drug. The implications of this model were discussed.