Drug delivery and transport to solid tumors

Purpose. The purpose of this review is to provide an overview of the principles of and barriers to drug transport and delivery to solid tumors. Methods. This review consists of four parts. Part I provides an overview of the differences in the vasculature in normal and tumor tissues, and the relationship between tumor vasculature and drug transport. Part II describes the determinants of transport of drugs and particles across tumor vasculature into surrounding tumor tissues. Part III discusses the determinants and barriers of drug transport, accumulation, and retention in tumors. Part IV summarizes the experimental approaches used to enhance drug delivery and transport in solid tumors. Results. Drug delivery to solid tumors consists of multiple processes, including transport via blood vessels, transvascular transport, and transport through interstitial spaces. These processes are dynamic and change with time and tumor properties and are affected by multiple physicochemical factors of a drug, multiple tumor biologic factors, and as a consequence of drug treatments. The biologic factors, in turn, have opposing effects on one or more processes in the delivery of drugs to solid tumors. Conclusion. The effectiveness of cancer therapy depends in part on adequate delivery of the therapeutic agents to tumor cells. A better understanding of the processes and contribution of these factors governing drug delivery may lead to new cancer therapeutic strategies.