Targeted Delivery of Dexamethasone

Stephen Massia (Inventor)

Research output: Patent

Abstract

Multivalent drug conjugates containing a targeting molecule. The goal of this work is achieve targeted delivery a pharmacologically active molecule inside cells expressing a certain profile of membrane proteins. In inflammation, endothelial cells exhibit increased levels of e-selectin, ICAM-1, VCAM-1, and many other proteins; in thrombosis, tissue-factor and many integrins are expressed; in cancerous cells, growth-factor-receptor expression increases; there are many other cases where specific proteins are expressed at a higher than baseline level. Many of these proteins are known to internalize either spontaneously or upon ligand binding to the protein. The internalization of these proteins can be used to a great advantage for the delivery of drugs into cells.With this technology, a drug conjugated to a molecule known to bind to a cell adhesion molecule such as e-selectin can be spontaneously delivered into the region of a cell where it can effectively reduce the disease state of a cell. The delivery is achieved by the natural-internalization of cell adhesion molecules into compartments on the cytoplasmic side of the diseased cell. When the cell adhesion molecule is internalized, the drug-targetting molecule conjugate is internalized with it. In our invention, novel-combinations of targeting molecules, drugs, and polymeric carriers are to be used. In some cases, the polymeric carrier will increase the efficacy of delivery. In other cases, the simpler monovalent form of the drug conjugated to the targeting molecule will be used. In all embodiments, unwanted delivery of drugs to non-pathological cells will be decreased or eliminated.
Original languageEnglish (US)
StatePublished - Jul 7 2006

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