Question

Delivery systems that are not eliminated by degradation, phagocytosis or glomerular filtration can leave the bloodstream by crossing the endothelium to reach target tissues. This occurs most readily in tissues with discontinuous endothelia, such as in liver tissues and many solid tumours90. Fenestrations in the liver sinusoidal endothelium permit particles of 100–200nm in diameter to exit the bloodstream and gain access to hepatocytes and other liver cells104,105. In some tumours, a combination of highly permeable endothelia and poor lymphatic drainage can lead to increased accumulation of circulating nanoparticles in malignant tissue — an occurrence termed the enhanced permeation and retention effect

WHAT IS THIS MEAN???IN EASIER WAT DETAIL.

Answer 1

When we want to deliver a drug or any other compound into a diseased system, for e.g. in cancer, we are concerned about whether the delivery medium, containing the molecule, would be trashed by the body's own filtering system, like glomerular filtration (a process by which our kidney filters out foriegn and toxic particles), phagocytosis (cellular engulfing of foreign particles and subsequent degradation) or other kinds of degradative cycles working within the body. Delivery systems which can avoid being eliminated/destroyed by these mechanisms, can penetrate through the enothelial lining of blood vessels and lymphatic vessels running through-out our body and enter the target tissue.

Liver is an organ where this mechanism frequently occurs. There are large gaps ('fenestrations') in the endothelial lining of the blood capillaries in liver ( the sinusoids), through which particles of 100–200nm in diameter can pass from the bloodstream into the cells of the liver tissue.

In cancer systems, the endothelial lining of blood vessels is highly compromised and becomes permeable. This is intended for the circulating cancer/tumor cells in the blood to move to distant organs and then leave the blood vessel in order to get settled within a growing tumor mass. Disrupted flow and accumulation of lymphatic fluid which courses through the body is also a feature of cancer. However, delivery systems can utilise these conditions, in order to leave the circulation and sneak out through the leaky endothelial linings, to enter the target cancerous tissue. A congested lymphatic fluid hold-up, along with such gaps in the fence (the endothelial lining), allows the nanoparticles to 'cross over the border' and accumulate within the cancerous/malignant tissue. This is called enhanced permeation and retention effect.