A reduction in the interstitial fluid pressure per se, does not enhance the uptake of the small molecule weight compound 5-fluorouracil into 4T1 mammary tumours

Abstract

The tumour interstitium represents a major barrier to drug delivery and modification of the tumour extracellular matrix (ECM) is one strategy that could promote better delivery. We have focused upon three factors in the tumour interstitium that could influence drug uptake into the tumour tissue; the interstitial fluid pressure (Pif), collagen content and the tumour blood vessel density (TBVD). Two treatment groups were used: repeated hyperbaric oxygen (HBO) and single HBO (both to 2.5 bar, 100% O2, à 90 min). The controls were exposed to normal atmosphere (1 bar, 21% O2). Pif, angiogenesis, collagen content and uptake of [H3]-5FU ([5-fluorouracil) was investigated. Pif and TBVD significantly decreased after hyperoxic treatment, without any change in collagen content. Uptake of 5FU was not affected by hyperoxic treatment. Reduction in Pif per se does not enhance the uptake of 5FU in 4T1 mammary tumours. The fibrotic ECM (unaltered collagen content) together with a less dense microvasculature might help explain this.