Drug delivery and transport to solid tumors.
OBJECTIVE
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.


CONCLUSIONS
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.
College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
Seong Hoon
SH
Jang
M Guillaume
MG
Wientjes
Dan
D
Lu
Jessie L S
JL
Au
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000502:physiology; D001692:Biological Transport; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers