1.8. Interstitial fluid pressure (IFP):
Abnormal lymphatic and blood vessels cause acidic pH, hypoxia, and high interstitial fluid pressure (IFP) in TME and elevated IFP is a key player in preventing adequate drug delivery to solid tumors [106]. Factors such as abnormal ECM, high cell density, disruption of lymphatic or venous drainage, and enhanced vascular permeability cause high IFP in the tumor [160]. Abnormal proliferation of cancer cells leads to mechanical compression of blood vessels and lymphatic vessels in the confined area of the microenvironment, subsequently, meager lymphatic drainage and poor blood flow are caused, leading to abnormal vascular structures and a further reduction in a number of functional lymphatic vessels [161]. As a result of excess fluid leakage from the vascular system into interstitial space or interstitium (where accumulates and swells the elastic ECM), IFP is increased, which is higher than in normal tissue [106].
The amount of drug entering the tumor and its absorption by cancer cells affects the efficacy of chemotherapy [162]. For a drug to reach cancer cells through blood vessels, it must be transferred from blood vessels to interstitial fluid and then from interstitial space to tissues [163]. Therefore, the amount of interstitial fluid pressure is important for drug delivery, and high IFP conditions can reduce drug transfer [162]. High IFP also compresses blood vessels, diverting blood away from the tumor center to the periphery, as a result, drug delivery is further reduced [162].