ABSTRACT
The chaotic blood flow in tumor vasculature and the heterogeneous vascular permeability of tumor blood vessels are among the key barriers controlling passive delivery of macromolecular and particulate delivery systems into the interstitium of solid tumors. Already compromised by abnormal hydrostatic pressure gradients, compressive mechanical forces generated by tumor cell proliferation cause intratumoral vessels to compress and collapse, thus creating further barriers for passive targeting. Liposomes are perhaps the best studied vehicles in cancer drug delivery, capable of either increasing the drug concentration in solid tumors and/or limiting drug exposure to critical target sites such as bone marrow and myocardium. Long-circulating liposomes have the capability to deliver between 3 and 10 times more drug to solid tumors compared with the administered drug in its free form. Nanoparticles assembled from synthetic polymers have also received much attention in cancer drug delivery. Polymer-based drug delivery systems favorably alter the pharmacokinetics and biodistribution of conjugated drugs and accumulate in tumor interstitium following extravasation.
