Table 3.

Summary of barriers to and strategies for improved drug delivery

Tumor microenvironment	Strategy
Desmoplastic, moderately permeable tumors (e.g., pancreatic ductal adenocarcinomas)	Stress alleviation
Hyperpermeable, nondesmoplastic tumors (e.g., subset of glioblastomas and ovarian carcinomas)	Vascular normalization
Hyperpermeable, desmoplastic tumors (e.g., a subset of mammary carcinomas)	Combined treatment
Drug	Delivery barrier
Small size (≤ 10 nm), low binding affinity	Perfusion-limited transport. Improved perfusion increases delivery.
Large size (> 10 nm), low binding affinity	Perfusion, transvascular, and interstitial limited transport. Improved perfusion increases delivery.
Any size, high binding affinity	Additional barrier to interstitial transport. Improved perfusion increases delivery but benefit may be compromised.