Tissue selective affinity targeting using the avidin-biotin system

Abstract

Selective delivery of biologically active substances is designed to overcome nonspecific biodistribution of drugs and increase their local concentration at the target tissue. Certain strategies are based on carrier-mediated delivery to selective tissues and organs through ligands recognized by receptors or other address molecules on target cells. Avidins offer an attractive approach to organ- or tissue-selective targeting. Avidin and streptavidin, two biotin-binding proteins, can be targeted to specific tissues when modified with appropriate tissue markers. Their resistance to proteolytic enzymes supports long-term accumulation at the target tissue or organ, and their biotin binding sites permit the delivery of biotinylated molecules or carriers loaded with cytotoxic drugs or other bioactive substances. Modification of the two proteins with tissue-specific markers (lactose for parenchymal and trinitrophenyl for nonparenchymal liver cells) resulted in high and prolonged accumulation in the target tissue. The modified proteins could target high doses of chemotherapeutic drugs (CDDP and 5-fluorouridine) to the liver through biotinyl dextran–derived carriers. Drug Dev. Res. 50:258–271, 2000. © 2000 Wiley-Liss, Inc.