A predictive model for calculating the electrostatic intercalation efficiency of methotrexate-loaded laponite dependent on clay concentration and pH built from binding constants

Abstract

The chemical species distribution diagram is a two-dimensional model (molar fraction vs pL) that provides information about the fractions of a molecule of interest in its free form, M, or bound to a ligand, L, to form the complex, M-L. The system presented in this research work involves the anticancer drug methotrexate, MTX, and the nanoclay laponite, Lap, represented as M and L respectively. Four systems with pH values: 1.63 ± 0.01, 3.34 ± 0.01, 4.81 ± 0.01, and 7.56 ± 0.01 were used to calculate of the conditional binding constants of the MTX-Lap complexes, in which the different chemical species of MTX predominate. The changes were followed spectrophotometrically and the data obtained were analysed using Stability Quotients from Absorbance Data (SQUAD) to determine these values. The Log β values obtained with SQUAD corresponding to the MTX-Lap complexes were: 4.92 ± 0.01, 4.38 ± 0.02, 3.60 ± 0.06, and 2.516 ± 0.007 corresponding to the pH values mentioned above. Plotting the logarithm of the conditional dissociation constant, Log K, as a function of pH gives a linear behaviour with the equation “Log K = -0.4149*pH + 5.6556” and R² of 0.9941. The Log K value of this linear relationship can be substituted by Log β. The Log β (pH dependent) is substituted into the mole fraction equations to obtain models that determine the molar percentages of free MTX and encapsulated MTX that depend only on pLap and pH. The mathematical model proposed in this research work is compared with experimental data to predict the percentage of free MTX as a function of nanoclay concentration and pH, with acceptable results.