Effects of tissue stretching or cell shrinkage on penetration depth of macromolecules in a rat fibrosarcoma

Interstitial penetration is critical for drug delivery in tumor tissues. To experimentally determine the penetration depth of macromolecules at the steady state, rat fibrosarcoma tissues were sectioned into 600 μm slices and incubated in solutions of dextrans with molecular weights of 10 kDa, 70 kDa, and 2000 kDa, respectively. After incubation, 10 μm cross-sections were taken and imaged to determine normalized steady-state concentration profiles as a function of molecular size. 10 kDa dextran had a relatively uniform concentration distribution. However, the concentration profile was nonuniform for 70 kDa dextran and the least uniform for 2000 kDa dextran. Stretching or incubation of tissues in 1 M mannitol solution improved the penetration of macromolecules in tissues. These results indicate that creating more interstitial space by either stretching or reducing cell size improves macromolecule distribution in tissues.