Passive Targeting

Passive targeting refers to the accumulation of drug or drug-carrier system at a particular site due to physicochemical or pharmacological factors. Permeability of the tumor vasculature increases to the point where particulate carriers such as nanoparticles can extravasate from blood circulation and localize in the tumor tissue.14,15 This occurs because as tumors grow and begin to outstrip the available supply of oxygen and nutrients, they release cytokines and other signaling molecules that recruit new blood vessels to the tumor, a process known as angiogenesis.16 Angiogenic blood vessels, unlike the tight blood vessels in most normal tissues, have gaps as large as 600-800 nm between adjacent endothelial cells. Drug carriers in the nanometer size range can extravasate through these gaps into the tumor interstitial space.17,18 Because tumors have impaired lymphatic drainage, the carriers concentrate in the tumor, resulting in higher drug concentration in the tumor tissue (10-fold or higher) than that can be achieved with the same dose of free drug. This is commonly referred to as enhanced permeability and retention, or the EPR effect.

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