Influence of hydralazine on interstitial fluid pressure in experi- mental tumors - a preliminary study

Background. Interstitial fluid pressure (IFP) has been recognised as the most important obstacle in macromolecular drug delivery to solid tumors. Our interest was to reduce differentialy tumor IFP with respect to IFP in surrounding and normal tissues in order to increase drug delivery to tumors as well to increase tumor blood flow and potentialy tumor tissue oxygenation. In this preliminary study we used hydralazine, a longacting arterial vasodilator. Materials and methods. Measurements of interstitial fluid pressure were performed in vivo on CBA mice bearing SAF tumors using wick-in-needle technique. Altogether eleven measurements were obtained on dif ferent animals with tumors of different size. Results. IFP in tumors after hydralazine administration was significantly lower than initial values in corresponding tumors. On average tumor IFP decreased for 33 % from initial value. On the contrary, no change in IFP in normal tissue was observed after hydralazine administration. Also, after injection of physiological saline instead of hydralazine there was no change in IFP neither in tumors nor in muscle. The results of our preliminary study on the effect of hydralazine on IFP in SAF tumor model is in accordance to previously reported studies. The decrease in tumor IFP was only observed in tumors, but not in muscle and surrounding subcutis. Conclusion. Hydralazine is a vasodilator which is capable of decreasing tumor IFP, reproducibly and with favorably long lasting dynamics.