Ilaria Casolaro

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.

Pulsed release of antidepressants from nanocomposite hydrogels

The pulsed release of three antidepressants (paroxetine, duloxetine, vortioxetine), loaded on two vinyl hydrogels bearing -amino acid residues (L-phenylalanine, L-valine) and embedded magnetic nanoparticles, was evaluated in different buffer solutions of purposely chosen pHs (2.9, 4.6, and 7.4). At low pH values the release of the drug was always small for a long period of days, and it underwent a sudden increase when a solution of pH 7.4 was maintained for a short period of hours. The releasing increase becomes much higher as greater was the residence time of the solution in contact with the hydrogel. The application of an alternating magnetic field (AMF) further increases the amount of drug released during the pH pulses. These different release variations were related to a different and reversible ability to swell of the hydrogel. The mechanism behind the process was mainly due to the different acid/base behaviour of the free carboxyl groups. Correspondence to: Mario Casolaro, Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, Siena 53100, Italy, Tel.: +39-0577-234388; E-mail: mario.casolaro@unisi.it

Antibacterial Properties of Silver Nanoparticles Embedded on Polyelectrolyte Hydrogels Based on α-Amino Acid Residues

Polyelectrolyte hydrogels bearing l-phenylalanine (PHE), l-valine (AVA), and l-histidine (Hist) residues were used as scaffolds for the formation of silver nanoparticles by reduction of Ag+ ions with NaBH4. The interaction with the metal ion allowed a prompt collapse of the swollen hydrogel, due to the neutralization reaction of basic groups present on the polymer. The imidazole nitrogen of the hydrogel with Hist demonstrated greater complexing capacity with the Ag+ ion compared to the hydrogels with carboxyl groups. The subsequent reduction to metallic silver allowed for the restoration of the hydrogel’s degree of swelling to the starting value. Transmission electron microscopy (TEM) and spectroscopic analyses showed, respectively, a uniform distribution of the 15 nm spherical silver nanoparticles embedded on the hydrogel and peak optical properties around a wavelength of 400 nm due to the surface plasmonic effect. Unlike native hydrogels, the composite hydrogels containing silver nanoparticles showed good antibacterial activity as gram+/gram− bactericides, and higher antifungal activity against S. cerevisiae.

Stimuli-Responsive Hydrogels Bearing amino acid Residues: a Potential Platform for Future Therapies

Vinyl hydrogels bearing α-aminoacid residues have been explored as platforms for the treatment of cancer, glaucoma and mood disorder therapies. Ionic/ionizable groups of the L-valine, L-phenylalanine and L-histidine residues are able to modify the swelling properties of the hydrogel on the basis of their thermodynamic characteristics. Greater basicity constants of functional groups improve a greater loading of the drug and a longer sustained-release pattern. The pH and the temperature affect the swelling of the hydrogel and increase ‘on demand’ the drug availability. A further stimulus based on alternating magnetic fields can be applied on hydrogels containing embedded magnetic nanoparticles used for site-specific controlled drug delivery. The diffusion process for the in vitro release of the drug (cisplatin, doxorubicin, pilocarpine, trazodone, citalopram and paroxetine) from the drugloaded hydrogels is mainly controlled by the drug-polymer interaction, that in the meanwhile preservs it’s bioactivity. The different interaction strength between the drug and the polymer may be a strategy to develop suitable capsules for long-term therapies.

CHAPTER 20:Multiple Stimuli-responsive Hydrogels Based on α-Amino Acid Residues for Drug Delivery

Vinyl hydrogels containing α-amino-acid (l-valine, l-phenylalanine, l-histidine) residues are endowed with unique stimulus-responsive properties and undergo large changes in swelling degree as a function of temperature, pH and ionic strength conditions or the intensity of an electric field. These biocompatible smart hydrogels exhibit single or multiple stimuli-responsiveness potentially useful for biomedical applications, including controlled drug delivery, bioengineering or tissue engineering. This chapter focuses on recent developments and future trends of the α-amino-acid-based hydrogels as drug- (cisplatin, temsirolimus, pilocarpine) delivery systems for cancer and glaucoma therapy, and as platforms for lithium ion delivery to the brain for bipolar disorder management.