New drug delivery systems to cross biological barriers based on the unique properties of carboranes
Polyhedal (car)boranes, can be considered as man-made inorganic analogues of aromatic hydrocarbons. Carboranes belong to newly emerging pharmacophores; successful biosteric replacement of phenyl rings was studied for several structurally diverse drugs from various indication groups. However, there is very little understanding about their penetration across biological membranes/barriers and their pharmacological properties. Recently we have observed some of them to cross readily and actively in vitro models of gastrointestinal and/or blood brain barriers, thus demonstrating a great opportunity to use them for designing drugs, diagnostics and BNCT agents with cell, tissue or organ selectivity. The aim of this project is to explore pharmacology of (car)boranes with various feasible substitutions, and in particular, to discover their capacity to cross gastrointestinal and/or blood-brain barrier, identify putative transporter responsible for active transport of boranes, and evaluate their broader utility in design of drugs active in multidrug resistant and/or brain cancers.