title: Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes.
abstract: This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the reversibility of the interaction, and the effect on the secondary structure of the macromolecule. Affinity constants of the counterionic condensation DNA-drug were in the order of 10⁶. The negative electrokinetic potential of DNA decreased with the increase of the proportion of loading drugs. The drugs were slowly released from the DNA-drug complexes and had release kinetics consistent with the high degree of counterionic condensation. The circular dichroism profile of DNA was not modified by complexation with atenolol, lidocaine, or timolol, but was significantly altered by the more lipophilic drugs benzydamine and propranolol, revealing modifications in the secondary structure of the DNA. The in vitro characterization of such interactions provides a physicochemical basis that would contribute to identify the effects of this kind of drugs in cellular cultures, as well as side effects observed under their clinical use. Moreover, this methodology could also be projected to the fields of intracellular DNA transfection and the use of DNA as a carrier of active drugs.
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina. lalarcon@fcq.unc.edu.ar.
authors.forename: Liliana P
authors.initials: LP
authors.lastname: Alarcón
authors.affiliation: Grupo de Investigación en Sistemas para Liberación Controlada de Moléculas Biológicamente Activas, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 30 # 45-03, Bogotá D. C. 111311, Colombia. ybaenaa@unal.edu.co.
authors.forename: Yolima
authors.initials: Y
authors.lastname: Baena
authors.affiliation: Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA), CONICET and Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba X5000HUA, Argentina. rubmanzo@fcq.unc.edu.ar.
authors.forename: Rubén H
authors.initials: RH
authors.lastname: Manzo
keywords: DNA; circular dichroism; complexation; drug interactions; physicochemical properties; polyelectrolytes; polymeric drug delivery systems