Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes

Scientia Pharmaceutica

Yolima Baena¹  Liliana P. Alarcón²  Rubén H. Manzo² 

[1] Grupo de Investigación en Sistemas para Liberación Controlada de Moléculas Biológicamente Activas, Departamento de Farmacia, Facultad de Ciencias, Universidad Nacional de Colombia, Carrera 3045-03, Bogotá D. C. 111311, Colombia;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;

关键词: polyelectrolytes;    DNA;    drug interactions;    complexation;    physicochemical properties;    circular dichroism;    polymeric drug delivery systems;   

DOI  :  10.3390/scipharm85010001

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown