Controlled Release of Antidepressant Drugs by Multiple Stimuli-Sensitive Hydrogels Based on α-Aminoacid Residues

Two slightly cross-linked hydrogels bearing l-phenylalanine (Phe-Nip3) or l-valine (Ava2) residues of a copolymeric and homopolymeric vinyl structure were considered for their potential application in the psychiatric treatment of depression. Two antidepressant drugs (citalopram and trazodone) were loaded into hydrogels and their controlled release behavior monitored for several days at 25 °C in two buffer solutions of different pHs (PBS pH 7.4 and acetate pH 4.6). The different basicity constants (logKs) of the involved substance determine a different electrostatic effect between the drug ionized positively and the negatively charged hydrogel. Both the hydrogels loaded with citalopram showed a greater binding effect with respect to trazodone. In fact, for the same hydrogel, the release of citalopram in PBS (4 days) was slower than trazodone (24 h). In addition, at pH (4.6) < logK the release of the drug was much slower and durable, due to the lower capacity of ionization and swelling of the hydrogel. Additionally, the magnetic nanoparticles (CoFe2O4) embedded into the hydrogel Phe-Nip3 were an additional remote control for drug release through the stimulation of an appropriate alternating magnetic field (AMF, 20 kHz and 50 W). In these conditions, the kinetics of the drug released was substantially increased