PHYSICOCHEMICAL CHARACTERIZATION OF A DOUBLE LONG-CHAIN CATIONIC AMPHIPHILE (VECTAMIDINE) BY MICROELECTROPHORESIS

We recently synthesized a novel cationic amphiphile utyl-N'-tetradecyl -3-tetradecylaminopropionamidine or Vectamidine (previously described as diC(14)-amidine)) that associates with DNA and RNA and facilitates their entry and expression into eukaryotic cells. Among several parame ters that have been shown to influence the transfection process, the s urface charge density plays a key role. Quantitative information about that charge density associated to the cationic amphiphiles organized in liposomal structure is not yet available. We provide here evidence by titration and microelectrophoresis measurements that an evaluation of the intrinsic acidity constants, the surface pH and the counterion binding constants allows to determine the charge density at physiologi cal pH of Vectamidine liposomes. The knowledge of this superficial cha rge is a prerequisite to a molecular understanding of the DNA-cationic amphiphile complex formation. The method described could be extended to any kind of cationic amphiphile. (C) 1998 Elsevier Science B.V. All rights reserved.