Polyelectrolyte Hydrogel Platforms for the Delivery of Antidepressant Drugs

Some vinyl hydrogels containing α-amino acid residues (l-phenylalanine, l-valine) were used as polyelectrolyte platforms for the evaluation of the controlled release of two antidepressants (paroxetine and duloxetine). The closer acidity constant (pKa) values of the two drugs show a closer release profile in physiological phosphate buffered saline (PBS) buffer (pH 7.40) and for long periods of time. The great electrostatic interaction forces between the COO^- group of the hydrogel and the protonated secondary amino nitrogen of the drug are the main factor improving the release kinetics; this release was found to be slower compared to that of two structurally related drugs bearing the tertiary amino nitrogen atom (citalopram and trazodone). Moreover, at the lower value of pH 4.60, paroxetine showed a flatter release profile from the hydrogel containing the l-phenylalanine residues that, after six days, is half of that shown by duloxetine. Further effects due to steric and hydrophobic interactions may contribute to the different release profile. A further stimulation with alternating magnetic fields (AMF) of low frequency (20 kHz/50 W) enhanced the release of the drug at pH 7.40 from the hydrogel containing magnetic nanoparticles. Both AMF and PBS solution at pH 7.40 were used to trigger the 'on-demand' pulsatile paroxetine release from the nanocomposite hydrogel.