title: Pharmacokinetic Modeling and Biodistribution Estimation Through the Molecular Communication Paradigm.
abstract: Targeted drug delivery systems (TDDSs) are therapeutic methods based on the injection and delivery of drug-loaded particles. The engineering of TDDSs must take into account both the therapeutic effects of the drug at the target delivery location and the toxicity of the drug while it accumulates in other regions of the body. These characteristics are directly related to how the drug-loaded particles distribute within the body, i.e., biodistribution, as a consequence of the processes involved in the particle propagation, i.e., pharmacokinetics. In this paper, the pharmacokinetics of TDDSs is analytically modeled through the abstraction of molecular communication, a novel paradigm in communication theory. Not only is the particle advection and diffusion, considered in our previous study, included in this model, but also are other physicochemical processes in the particle propagation, such as absorption, reaction, and adhesion. In addition, the proposed model includes the impact of cardiovascular diseases, such as arteriosclerosis and tumor-induced blood vessel leakage. Based on this model, the biodistribution at the delivery location is estimated through communication engineering metrics, such as channel delay and path loss, together with the drug accumulation in the rest of the body. The proposed pharmacokinetic model is validated against multiphysics finite-element simulations, and numerical results are provided for the biodistribution estimation in different scenarios. Finally, based on the proposed model, a procedure to optimize the drug injection rate is proposed to achieve a desired drug delivery rate. The outcome of this study is a multiscale physics-based analytical pharmacokinetic model.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Chahibi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pierobon
authors.forename: Ian F
authors.initials: IF
authors.lastname: Akyildiz
mesh_terms: D001783:Blood Flow Velocity; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D016503:Drug Delivery Systems; D006801:Humans; D008297:Male; D008955:Models, Cardiovascular; D010599:Pharmacokinetics; D014018:Tissue Distribution