Fenestrated sinusoidal capillaries

Figure 8.3 Natural (a, b) and synthetic (c, d) nanopattems that offer templates for MSC differentiation and self-renewal (a) Type X collagen and (b) fenestrated sinusoidal capillaries, (c) dip-pen patterned nanoislands (70 nm diameter with 28 mn center-center spacing) that retain MSC multipotency, and (d) self-assembled helical amphiphUe with 63 nm periodicity that stimulates MSC osteogenesis.

Figure 5.1 Schematic illustration of the structure of the wall of different classes of blood capillaries. (1) Continuous capillary (as found in the general circulation). The endothelium is continuous with tight junctions between adjacent endothelial cells. The subendothehal basement membrane is also continuous. (2) Fenestrated capillary (as found in exocrine glands and the pancreas). The endothelium exhibits a series of fenestrae which are sealed by a membranous diaphragm. The subendothehal basement membrane is continuous. (3) Discontinuous (sinusoidal) capillary (as found in the liver, spleen and bone marrow). The overlying endothelium contains numerous gaps of varying size. The subendothehal basement is either absent (hver) or present as a fragmented interrupted structure (spleen, bone marrow)...

Due to their large molecular weight (> 1,000 kDa) and hydrodynamic diameter in aqueous suspension of 100 nm, plasmids extravasate poorly via continuous capillaries because of tight junctions between the cells. However, plasmids can easily extravasate to sinusoidal capillaries of liver and spleen. Formulating plasmids into unimeric particles of 20-40 nm in diameter may enhance extravasation of plasmids across continuous and fenestrated capillaries. 

Capillaries are the exchange vessels of the body. They have structural variations to allow different levels of metabolic exchange (of exogenous and endogenous substances) between blood and the surrounding tissues. The structure of the walls varies depending on their resident tissue. There are three major types of blood capillaries continuous fenestrated and sinusoidal (discontinuous) [1] ... 

In addition molecules have been identified on continuous endothelium that facilitate binding of albumin to endothelium, increase capillary permeability, and theoretically can increase paracellular transport or transcytosis of albumin-bound molecules. An example of this is the gp60 albumin-binding glycoprotein molecule identified on continuous endothelium in multiple tissues (heart, lung, skeletal muscle, adipose, peritoneum, and intestinal smooth muscle) but absent from continuous endothelium in cerebral cortex, and sinusoidal or fenestrated endothelium in liver, adrenal, pancreas, and intestinal lamina propria [21,22],... 

Capillary Fenestrations large in liver pores sinusoids... 

Soluble macromolecules of both natural and synthetic origins have been used as drug carriers. When compared with the particulate carriers, soluble macromolecules (i) encounter fewer barriers to their movement around the body and can enter into many organs by transport across capillary endothehum or in the liver by passage through the fenestration connecting the sinusoidal lumen to the space of Disse (ii) penetrate the cells by pinocytosis, which is a phenomenon universal to aU cells and which, unlike phagocytosis, does not require an external stimulus and (Hi) can be found in the blood many hours after their introduction (particulate carriers, in contrast, are rapidly cleared from the blood by the RES). The fate of soluble macromolecules in animals and humans, with special reference to the transfer of polymers from one body compartment to another, has been reviewed by Drobnik and Rypacek (67). 

Hepatocytes are the commonest cell type found in the liver, constituting about 70% of the total liver mass. The plasma membranes of these cells have three functional domains the sinusoidal domain, an intercellular domain with gap junctions that is the contact area between hepatocytes, and the canalicular domain, where many of the hepatic secretory functions are performed. The hepatocytes are arranged in single cell layers around sinusoids, which are vascular capillary vessels connected to the hepatic portal vein and hepatic artery the perisinusoidal space of Disse separates the endothelial cell from the hepatocytes. Fenestrations (or windows) in the cells lining the sinusoids allow the formation of hepatic lymph fluid and the movement of proteins into the space of Disse. The lymph leaves the liver through the lymphatic vessels, the lymph nodes, and the thoracic duct, although a small proportion leaves the liver through lymph vessels associated with the hepatic vein. 

Particle size. Particles greater than 7 pm are larger than blood capillaries ( 6 pm) and become entrapped in the capillary beds of the lungs (which may have fatal effects). The majority of particles that pass the lung capillary bed accumulate in the elements of the RES (spleen, liver and bone marrow). The degree of splenic uptake increases with particle size. Removal of particles > 200 nm is due to a non-phagocytic process (physical filtration) in the spleen and phagocytosis (by Kupffer cells) by the liver. Particles < 200 nm decreases splenic uptake and the particles are cleared by the liver and bone marrow. Colloidal particles not cleared by the RES can potentially exit the blood circulation via the sinusoidal fenestration of the liver and bone marrow. 

---