Effect of hydralazine on interstitial fluid pressure in experimental tumours and in normal tissue.
Interstitial fluid pressure (IFP) has been recognised as the most important obstacle in macromolecular drug delivery to solid tumours. The aim of our study was to measure the IFP simultaneously in tumour and in muscle or in subcutis and to determine whether injection of hydralazine reduces differentially tumour IFP with respect to IFP in surrounding and normal tissues. In addition, it was of interest whether the decrease in IFP due to hydralazine depends on tumour volume and/or on initial IFP. Measurements of IFP were performed by means of the wick-in-needle technique and they were obtained on tumours of different size. In both tumour models, hydralazine significantly reduced the pretreatment IFP level. On average IFP decreased by 31% and 14% from the initial value in SAF and LPB tumours, respectively. On the contrary, hydralazine did not decrease IFP in normal tissue. Injection of NaCl solution instead of hydralazine had no effect on IFP either in tumours or in subcutis/muscle. The results of our study on the effect of hydralazine on IFP in SAF and LPB tumour model are in accordance to previously reported studies. The initial IFP in tumour is positively-correlated with the tumour size, while the decrease in the tumour IFP is independent of the initial IFP value. In addition, the decrease in tumour IFP is not correlated to tumour volume.
Podobnik
B
B
University of Ljubljana, Faculty of Electrical Engineering, Trzaska 25, 1000 Ljubljana, Slovenia.
Sersa
G
G
Miklavcic
D
D
D000818:Animals; D005110:Extracellular Space / Q000187:drug effects*; D005260:Female; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D011312:Pressure; D015203:Reproducibility of Results; D012513:Sarcoma, Experimental / Q000503:physiopathology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014665:Vasodilator Agents; D006830:Hydralazine; D012965:Sodium Chloride