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Receptor and Absorptivemediated Uptake

Macromolecules such as polypeptides and proteins are excluded from uptake by diffusion or through pores at the BBB. However, the presence of receptor-mediated uptake and transport into the brain has been found for a number of substances. Specific receptors for insulin and transferrin were initially described. These receptors have been identified at the molecular level as being identical to their counterparts in peripheral tissues 35,36 . However, at the BBB the receptors mediate transcytosis of...

Pathological Processes in the Colon

Ulcerative or inflammatory lesions may affect the physiology of the small and large intestine. Ulcer formation entails a circumscribed loss of tissue from the surface of an organ, which results from necrosis following cell destruction by chemicals and the like, or by restriction of the blood supply. Ulcers are among the most common and important lesions. Those that do not penetrate the muscularis mucosa are called erosions. Ulcerative conditions in humans must be differentiated from malignant...

Vectormediated Delivery

In this approach, 'chimeric peptides' 79 are generated as transportable drug derivatives targeting the receptor-mediated mechanism. Chimeric peptides are formed by linking a drug that is unable to cross the BBB to a vector (see Figure 2.8). Binding of the vector at the lu-minal membrane of brain capillary endothelial cells initiates receptor-mediated or adsorp-tive-mediated transcytosis (Figure 2.3c). Size and structure of the cargo may vary as long as binding and cellular uptake of the vector...

Bispecific Monoclonal Antibodies

Another approach to selectively inducing tumour cell killing is by the use of bispecific monoclonal antibodies BsMAb .They combine the specificity of two separate antibodies within one molecule and cross-link an effector killer cell or a toxic molecule with the target cell to be destroyed 75 . There are three major approaches for creating BsMAbs. They can be obtained by chemical cross-linking of two MAbs, by fusing two hybridomas 76 , or by genetic engineering 77 . Each method has its...