Micro-Pharmacology: Recognizing and Overcoming the Tissue Barriers to Drug Delivery

Systemic chemotherapy is one of the main anticancer treatments used for most kinds of clinically diagnosed tumors. However, the efficacy of these drugs can be hampered by the physical attributes of the tumor tissue, such as tortuous vasculature, dense and fibrous extracellular matrix, irregular cellular architecture, metabolic gradients, and non-uniform expression of the cell membrane receptors. This can impede the transport of therapeutic agents to tumor cells in quantities sufficient to exert the desired effect. In addition, tumor microenvironments undergo dynamic spatio-temporal changes during treatment, which can also obstruct the observed drug efficacy. To examine ways to improve drug delivery on a cell-to-tissue scale (single-cell pharmacology), we developed the microscale pharmacokinetics/pharmacodynamics modeling framework “microPKPD”. I will present how this framework can be used to design optimal schedules for various treatments and to investigate the development of drug-induced resistance.