Abstract
Purpose. To determine the mechanism and identify forces of interactionbetween polyaspartic acid and diminazene (a model drug). Such knowledgeis essential for the design of polymeric drug delivery systemsthat are based on molecular self-assembly into complexes or micellartype systems.
Methods. Complex formation was studied by isothermal titrationmicrocalorimetry and the McGhee von Hippel model was applied toobtain K obs, ΔH obs, and n obs. The calorimetry data were compared withboth an optical density study and the amount of free/complexed drug.
Results. The diminazene-polyaspartic acid interaction is enthalpicallydriven, whereby one diminazene molecule interacts with two monomersof polyaspartic acid. The dependence of K obs on saltconcentrationreveals a contribution of electrostatic interactions. However, applyingManning's counter ion condensation theory shows that the major drivingforce for the complex formation is hydrogen bonding, with interfacialwater molecules remaining buried within the complex. Themodelling of the pH dependence of K obs and ΔH obsdemonstrates thatthe ionization of carboxylic groups of polyaspartic acid is a prerequisitefor the interaction.
Conclusions. Complex formation between diminazene and polyasparticacid is driven by both electrostatic interactions and hydrogen bonding,with the latter being the dominating force. Although electrostaticinteractions are not the major driving force, ionization of the drug andpolymer is essential for complex formation.
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Ehtezazi, T., Govender, T. & Stolnik, S. Hydrogen Bonding and Electrostatic Interaction Contributions to the Interaction of a Cationic Drug with Polyaspartic Acid. Pharm Res 17, 871–877 (2000). https://doi.org/10.1023/A:1007520628237
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DOI: https://doi.org/10.1023/A:1007520628237