Asymmetric bolaamphiphiles from vernonia oil designed for drug delivery

Abstract

Throughout the ages, fats, oils and their chemical derivatives have been used in a variety of medical applications, but currently they are becoming important as components in drug delivery systems. Liposomes (vesicles from phospholipids) are among the lipid-based delivery systems that have been most extensively studied. However, targeting of liposomes to specific tissues is still problematic, and attempts to overcome these limitations include developments in nano-sized monolayer vesicles made of bolaamphiphiles (compounds containing two hydrophilic headgroups at each end of an alkyl chain). This paper describes bolaamphiphile synthesis and characterization of the nano-sized vesicles formed from the bolaamphiphiles with potential application for targeted drug delivery to the brain. The starting material for the synthesis is vernonia oil (or its fatty acids or methyl esters), which is a naturally epoxidized triacylglycerol obtained from the seeds of Vernonia galamensis. The targeting mechanism is based on the hydrolysis of the amphiphile's headgroup by an enzyme abundant in the target tissue, with subsequent release of the encapsulated drug at the target site. Preliminary experiments in mice demonstrated that the marker FITC-dextran, which normally does not penetrate the blood brain barrier, is delivered into the brain when encapsulated in these vesicles.