Complex Formation Between The Anionic Polymer (PAA) and a Cationic Drug (Procaine HC1): Characterization by Microcalorimetric Studies

Purpose. Due to the importance of drug-polymer interactions in, inter alia, drug loading/release, supramolecular assemblies and DNA delivery for gene therapy, the aim of this study was therefore to establish the mechanism of interaction between a model polymer (Polyacrylic acid, PAA) and a model drug (procaine HCl). Methods. This was performed by studying the effect of salt (KCl) concentration on their heat released values using Isothermal Titration Microcalorimetry (ITM). The integrated released heat data were computer fitted to a one class binding model and the thermodynamic parameters (K_obs, H, and N) were determined. Results. As the KC1 concentration was increased, K_obs decreased thus establishing the salt dependence of the interaction. The linear variation of G_obs with S_obs indicated that their interaction was entropically driven. The stoichiometry of the interaction was calculated to be one procaine molecule per monomer of PAA. Dissection of the total observed free energy at each KC1 concentration indicated that the contribution of the non-electrostatic attractions to the interaction of PAA with procaine HC1 was greater than those of the electrostatic attractions. Conclusions. We have shown that the interaction between PAA and procaine HC1 is dependent upon the presence of counterions (monovalent ions) and is mainly entropically driven. The calculated stoichiometry indicated that one procaine HC1 molecule neutralised one carboxylic acid group on PAA. Although electrostatic interactions were necessary for initiating complex formation, the non-electrostatic forces were dominant in stabilising the PAA-procaine HC1 complex.