![]() Other biologically active proteins, such as insulin and immunoglobulin G, are actively transcytosed through BBB endothelial cells. Brain cells require a constant supply of iron to maintain their function and the brain may substitute its iron through transcytosis of iron-loaded Tf across the brain microvasculature. An example of this is the transport of transferrin (Tf) across the BBB. In addition to the unidirectional and bidirectional transport of small molecules, other macromolecules are able to enter the brain tissue from the blood by a receptor-mediated process. Knowledge of BBB characteristics, therefore, is important for understanding the mechanisms of drug delivery to the CNS. Figure 1 shows a simplified scheme of the passage of substances across the BBB.Ĭompared with the vasculature of many other organs, the normal BBB severely restricts the passage of most drugs from plasma to the extracellular space, with more than an 8-log difference in the entry rate of small, lipid-soluble molecules compared with large proteins. Brain microvascular endothelial cells, which constitute the anatomical basis of BBB, form tight junctions due to a lack of fenestration and reduce the diffusion of molecules across the vessels. Several carrier or transport systems, enzymes and receptors that control the penetration of molecules in the BBB endothelium have been identified. Recent cell and molecular biology studies have provided new insights into the function of the BBB. The classically accepted function of the BBB is to protect the brain against the entry of noxious agents. The previous theory that the blood–brain barrier (BBB) is a passive impermeable barrier that segregates blood and brain interstitial fluid has given way to the concept that the BBB is a dynamic conduit for transport between the blood and the brain for nutrients, peptides proteins and immune cells. Although there are currently some limitations and concerns for the potential neurotoxicity of NPs, the future prospects for NP-based therapeutic delivery to the brain are excellent.įor over a century it has been recognized that the entry of certain substances into the brain is restricted. An important application of nanobiotechnology is to facilitate the delivery of drugs and biological therapeutics for brain tumors across the BBB. Some strategies require multifunctional NPs combining controlled passage across the BBB with targeted delivery of the therapeutic cargo to the intended site of action in the brain. This review describes various nanoparticle (NP)-based methods used for drug delivery to the brain and the known underlying mechanisms. Among the various approaches that are available, nanobiotechnology-based delivery methods provide the best prospects for achieving this ideal. ![]() The ideal method for transporting drugs across the BBB should be controlled and should not damage the barrier. Several strategies have been employed to deliver drugs across this barrier and some of these may do structural damage to the BBB by forcibly opening it to allow the uncontrolled passage of drugs. ![]() The blood–brain barrier (BBB) is meant to protect the brain from noxious agents however, it also significantly hinders the delivery of therapeutics to the brain.
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