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].