T. Ehtezazi et al., Hydrogen bonding and electrostatic interaction contributions to the interaction of a cationic drug with polyaspartic acid, PHARM RES, 17(7), 2000, pp. 871-878
Purpose. To determine the mechanism and identify forces of interaction betw
een polyaspartic acid and diminazene (a model drug). Such knowledge is esse
ntial for the design of polymeric drug delivery systems that are based on m
olecular self-assembly into complexes or micellar type systems.
Methods. Complex formation was studied by isothermal titration microcalorim
etry and the McGhee von Hippel model was applied to obtain K-obs, Delta H-o
bs, and n(obs). The calorimetry data were compared with both an optical den
sity study and the amount of free/complexed drug.
Results. The diminazene-polyaspartic acid interaction is enthalpically driv
en, whereby one diminazene molecule interacts with two monomers of polyaspa
rtic acid. The dependence of K-obs on salt concentration reveals a contribu
tion of electrostatic interactions. However, applying Manning's counter ion
condensation theory shows that the major driving force for the complex for
mation is hydrogen bonding, with interfacial water molecules remaining buri
ed within the complex. The modelling of the pH dependence of Kobs and Delta
H-obs demonstrates that the ionization of carboxylic groups of polyasparti
c acid is a prerequisite for the interaction.
Conclusions. Complex formation between diminazene and polyaspartic acid is
driven by both electrostatic interactions and hydrogen bonding, with the la
tter being the dominating force. Although electrostatic interactions are no
t the major driving force, ionization of the drug and polymer is essential
for complex formation.