A feature of endothelial cells within the lung and heart is the presence of a large number of caveolae (“little caves”), which seem to play a role in transendothelial transport. Another specialized endothelium is that found in the glomerulus, where fenestrae are found that permit small solutes to be filtered into the renal tubules, while excluding proteins and cells larger than 5–10 nm in diameter. For example, in tissues such as liver and spleen, the endothelium has large openings (hundreds of nanometers – microns in size) permitting movement of larger objects out of the bloodstream. The phenotype of endothelial cells is different within organs and larger vessels. Finally, the tunica adventitia is a layer that consists of microvasculature within the vessel wall, such as the vasa vasorum. In different portions of the vasculature, the tunica media has different compositions. veins and arteries), the tunica intima is surrounded by a layer known as the tunica media, which consists of smooth muscle cells, which regulate features such as vascular compliance. The tunica intima consists of endothelial cells and a basal membrane, which is the only component of the endothelium in capillaries. These highly specialized cells function in concert with other components of the barrier to form the endothelium. The endothelium provides an extremely large surface area for drug delivery.Įndothelial cells are the primary component of the endothelial lining of the circulatory systems (blood and lymphatic), heart (chambers and valves), and cavities in the central nervous system (brain ventricles). ), is the key target for therapeutic interventions in many conditions. Furthermore, endothelium, which represents an enormously extended surface area accessible to blood (3000–6000 m 2, Fig. Yet, even large, micron-sized, long-circulating DDS having favorable PK enter some extravascular sites normally (e.g. Generally, endothelium less effectively restricts diffusion to tissues of small drugs vs. The degree of restriction of access to extravascular sites depends on the permeability characteristics of endothelial cells typical of a given vascular area under conditions of a specific pathology, as well as PK and other features of circulating agents, such as size. The endothelium exists as a lining surrounding the lumen of all blood vessels – arteries, arterioles, capillaries, venules, and veins separating blood from tissues. The rapidly growing roster of DDS devised to improve pharmacokinetics (PK), tissue distribution, and effects of drugs includes molecular carriers (e.g., antibodies, peptides, sugars, polyethylene glycol (PEG)), multimolecular carriers (e.g., liposomes and other nanocarriers), cells, and fragments derived from cells. Blood flow transports drugs and drug delivery systems (DDS). We discuss the design of endothelial-targeted nanocarriers, factors underlying their interactions with cells and tissues, and describe examples of their investigational use in models of acute vascular inflammation with an eye on translational challenges.ġ. Introduction: Vascular endothelium and drug deliveryĬirculation of blood through the vascular system represents the main mechanism for distribution of pharmacological formulations administered via intravascular, intramuscular, and other types of injections, and delivered via oral, pulmonary, nasal, sublingual, and other routes. Three decades of research efforts have focused on specific vascular targeting, which have yielded a multitude of DDS, many of which are currently undergoing a translational phase of development for biomedical applications, including interventions in the cardiovascular, pulmonary, and central nervous systems, regulation of endothelial functions, host defense, and permeation of vascular barriers. Circulating DDS may accumulate in the vascular areas of interest and in off-target areas via mechanisms bypassing specific molecular recognition, but using ligands of specific vascular determinant molecules enables a degree of precision, efficacy, and specificity of delivery unattainable by non-affinity DDS. Endothelial cells, which line the luminal surface of the vasculature, play a tripartite role of the key target, barrier, or victim of nanomedicines in the bloodstream. In many cases, components of the vascular system represent therapeutic targets. The bloodstream is the main transporting pathway for drug delivery systems (DDS) from the site of administration to the intended site of action.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |