Physiological Transport Mechanisms for Peptides and Proteins at the Blood Brain Barrier

As opposed to the delivery strategies discussed above, which are primarily aimed at short-term application in the treatment regimens of malignant brain tumors, drug treatments of chronic degenerative disorders will require long- term application of the therapeutic agent. This implies the need to develop a noninvasive approach for brain delivery via the systemic route. To this end, utilization of endothelial transport mechanisms is being explored in preclinical studies. For macromolecules, the...

The Role of Brain Extracellular Fluid Production and Efflux Mechanisms in Drug Transport to the Brain

Begley, Ehsan Ullah Khan, Christopher Rollinson, and Joan Abbott King's College London, London, England INSERM U26, Hopital Fernand Widal, Paris, France The in vivo penetration of drugs into the central nervous system (CNS) is usually quantified by experimentally determining the brain content of drug with time to derive an influx constant (microliters per milligram of tissue per minute) or permeability coefficient (centimeters per second). Most in vivo experimental methods describing...

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The Relevance of P-Glycoprotein in Drug Transport to the Brain The Use of Knockout Mice as a Model System University Clinic Eppendorf, Hamburg, Germany P-glycoprotein (Pgp) was first discovered in the 1970s in malignant tumor cells (1). As a cell membrane protein it confers resistance to certain cytostatic agents by removing potentially toxic substances in an energy-dependent transport process as soon as they gain entry to the cells (multidrug resistance, MDR). In the treatment of hematological...

Drug Delivery by Chimeric Peptides

The opportunity for drug delivery arises from the possibility to synthesize ''chimeric peptides'' (60). These are generated by linking a drug that lacks transport at the BBB to a vector. Binding of the vector at the luminal membrane of brain capillary endothelial cells initiates receptor-mediated or adsorp-tive-mediated transcytosis. The mode of delivery was schematically visualized in Fig. 1. Size and structure of the cargo may vary as long as the drug moiety does not inhibit binding and...