Tumor interstitium drugs

Two major steps in drug delivery are commonly considered first step is the tissue vascular level (organ), accomplished by EPR effect for polymer therapeutics (nanomedicine) which can traverse the vascular wall to the tumor interstitium, where EPR effect plays the single most important role [69]. 

Active targeting can also enhance the distribution of nanomedicine within the tumor interstitium (Drummond et al. 1999). Active targeting has been explored to deliver drugs into resistant cancer cells (Sapra and AUen 2003). 

FIGURE 2.4.5 (a) Illustration of the use of TAT as an example of a CPP to demonstrate the concept of deactivation of a CPP in the blood compartment and its activation in the tumor interstitium or cells for in vivo tumor-targeted drug delivery, (b) Amidization of TAT s primary amines to succinyl amides and their acid-triggered hydrolysis [65]. 

Figure 3. A detailed depiction of a tiny section (C in Figure 1) of this tumo11 showing tumor cells, interstitium, a small blood vessel and the route that a drug i the chemotherapeutic treatment takes. Adapted from Jain.45...

Alternatively, if the tumor vasculature could be made the target, then the drugs would not have to cross the vessel wall or the interstitium. Anti-angiogenesis therapy, pioneered by Judah Folkman (1993), whose aim is to stop the growth of new vessels of a tumor, is a successful example of such an approach. Hyperthermia, photodynamic therapy, and cytokines such as TNF are other approaches which may also impair the tumor blood supply. One attractive hypothesis is that when several of the current cytotoxic therapies work, it is not only because they destroy cancer cells, but also because they may destroy a solid tumor by impairing its blood supply. Thus judiciously combining anti-vascular therapies with anti-cellular therapies may lead to synergistic results. Our recent study with lym-... 

Controlled-release polymer implants are useful for delivering drugs directly to the brain interstitium. This approach may improve the therapy of brain tumors or other neurologieal disorders. The mathematical models described in this section—which are based on methods of analysis developed in earlier chapters—provide a useful framework for analyzing mechanisms of drug distribution after delivery. These models describe the behavior of chemotherapy compounds very well and allow prediction of the effect of changing properties of the implant or the drug. More complex models are needed to describe the behavior of macromolecules, which encounter multiple modes of elimination and metabolism and are subject to the effects of fluid flow. 

---