On the use of ion-pair chromatography to elucidate doxorubicin release mechanism from polyalkylcyanoacrylate nanoparticles at the cellular level.

The major hypothesis underlying the remarkable efficiency of polyalkylcyanoacrylate particles loaded with doxorubicin against multidrug resistant tumor cells in vitro, is based on the ion-pair association of doxorubicin with soluble hydrolysis products of polyalkylcyanoacrylate. In an attempt to demonstrate the validity of this hypothesis, we have used ion-pair reversed-phase high-performance liquid chromatography and a laboratory-synthetized compound, i.e., the 2-cyano-2-butylhexanoic acid, as a model for polyalkylcyanoacrylate highly polydispersed degradation products. It is shown that, compared to a counter-ion, like heptane sulfonic acid, 2-cyano-2-butylhexanoic acid exhibits an effective ion-pairing effect at different pH values and organic mobile phase conditions. Moreover, at pH close to physiological conditions and at low mobile phase organic modifier percentage, this effect is experimentally observed, which strongly supports the initial hypothesis.