Biomaterials modeling of localized hyperthermia and drug delivery for breast cancer.

摘要

Biomaterials involving life, could be bio-derived or bio-inspired and have properties and characteristics that are quite complex to be adequately synthesized and analyzed by deterministic methods. Probabilistic modeling tools provide necessary insights and understanding of mechanisms and processes induced and/or integrated in them for purposes of applications in biology, medicine and engineering. The hypothetical additive and synergistic effects potentiated by the common cellular targeting of the microtubule stabilization are eroded depending on the heat delivery temperature, Paclitaxel nanoparticles (Taxol) concentration and sequence of application. The purpose of the study was to provide better predictive understanding of the effects of hyperthermia (41° to 45°C), Paclitaxel nanoparticles ( Taxol) and their synergistic combination on the growth and shrinkage of MDA-MB-231 cells. As an application of the study, characterization of the temperature pattern distribution from the recently fabricated implantable hyperthermia device was achieved in a monolayer of these cells. Overall, the more nonlinear exponentiated polynomial quotient response Z (QRZ)-models with degree (K+1) contextually modeled the phenomenon of hyperthermia (physically illustrated by use of Isohypethermals) and the live cell count response to Taxol in both early and late cell generations. The mixed log-normal and exponential multiparameter QRZ-model effectively predicted the peripheral temperature developed by the newly fabricated implantable hyperthermia Microdevice. The model predictive power and the unit change effects of the drug concentration and exposure times based on the developed QRZ-model were best characterized using chemographs. The study provided improved understanding of the effect of combined hyperthermia (41° to 45°C) and Paclitaxel nanoparticles from a quantitative point of view. Temperatures below 43°C did not adequately inhibit growth of the most invasive MDA-MB-231 cell line. Contrastingly, growth of cancer cells was completely inhibited by temperatures at and above 43°C. It has been demonstrated for the first time by use of Isochemotherapy curves the existence of the minimum critical hyperthermic temperature (MCHT) of 43°C. This finding gives the potential temperature for the synergistic outcome of simultaneous application of both hyperthermia and Taxol in treatment of breast cancer. Depending on the temperature regime for the combinational therapy either below 43°C or at and above 43°C, drug diffusion or heat transfer and diffusion becomes dominant cell-killing agent, respectively.