ASSOCIATION OF CHLOROQUINE INTO MIXED MICELLES SDS/TRITON X-100: EFFECT OF SUPERFICIAL CHARGE OF THE MICELLE

FQ4

Rodrigues,RZ; Del Lama, MPFM; Naal, RMZG

Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo - USP, Ribeirão Preto - SP

Introduction: Most drugs used in the malaria treatment, such as chloroquine (CQ), cause phototoxic side effects in skin and eyes (regions rich in melanin), that is attributed to the complex formed by chloroquine-melanin. Chloroquine is also used in the treatment of lupus erythematosus, rheumatoid arthritis and Aids. However, not much is known about the mechanisms responsible for photosensitivity caused by this drug. CQ is a prototropic drug that, depending on pH, can exist in different forms: neutral, monoprotonated or diprotonated. The mixed micelles of SDS and Triton-X-100 will be used to mimetic the biological membrane, which presents a surface density of charge that changes with the location in the body. Objective: The goal of this work is to contribute to the elucidation of the antimalarial action mechanisms in biological systems. Materials and Methods: The critical micellar concentrations (CMC) of mixed micelles formed by SDS (anionic surfactant) and Triton-X-100 (non-ionic surfactant) (α_SDS=0; 0.2; 0.4; 0.5; 0.6; 0.8 and 1.0 – final concentration 50 mM) were determined, using pyrene as fluorescent probe, in order to know the concentration which is formed the micellar aggregate in each pH. The pKa₁ of CQ, in mixed micelles were obtained by simulation of the curves of absorbance versus pH. The binding constants (Kb) of CQ in mixed micelles were obtained through the simulation of the curves of fluorescence versus concentration of surfactants in the mixture. The wavelengths for excitation and emission were equal to 342 and 390 nm, respectively, and slits of 5nm. All the experiments were performed in water and borate/citrate/phosphate buffer, 50 mM, in pH 5, 7.5, 9 and 13. The β-parameter for mixed micelles SDS/Triton-X-100 was determined by Rubingh’s Method (Rubingh, D.N. Solution Chemistry of Surfactants; Mittal, K.L., Ed. Plenum Press: New York, 3, 337, 1997). Results and Discussion: CMC values decreases with the molar fraction of Triton-X-100 for all micellar compositions, independent of the pH. The negative value for the β parameter (-3.05) showed the existence of synergism between the surfactants used. The pka₁ of the CQ, in homogeneous medium, was 8.55, while in micelles formed by SDS or Triton X-100, the pka₁ were 9.61 and 7.95, respectively. This behavior indicates the superficial charge of micelle can select the different forms of the CQ. For mixed micelles, it was observed the pKa₁ decreases slowly with molar fraction of SDS. The association of CQ with mixed micelles decreases with the molar fraction of Triton-X-100 reducing the binding constant, Kb. Conclusion: The results obtained for pKa₁ and Kb suggest the electrostatic effect is the most important force, responsible for modulation of the prototropic forms of CQ and their association with micelles.