Characterization of a new class of DNA delivery complexes formed by the local anesthetic bupivacaine

Bupivacaine, a local anesthetic and cationic amphiphile, forms stable lipos omal-like structures upon direct mixing with plasmid DNA in aqueous solutio ns. These structures are on the order of 50 70 nm as determined by scanning electron microscopy, and are homogeneous populations as analyzed by densit y gradient centrifugation. The DNA within these structures is protected fro m nuclease degradation and UV-induced damage in vitro. Bupivacaine:DNA comp lexes have a negative zeta potential (surface charge), homogeneous nature, and an ability to rapidly assemble in aqueous solutions. Bupivacaine:DNA co mplexes, as well as similar complexes of DNA with other local anesthetics, have the potential to be a novel class of DNA delivery agents for gene ther apy and DNA vaccines. (C) 2000 Elsevier Science B.V. All rights reserved.