title: Long-term doxorubicin release from multiple stimuli-responsive hydrogels based on α-amino-acid residues.
abstract: We have developed a series of pH- and temperature-stimuli-sensitive vinyl hydrogels, bearing α-amino acid residues (L-phenylalanine, L-valine) and incorporating magnetic nanoparticles of different chemical compositions (CoFe2O4 and Fe3O4). The goal was to study the potential applications of these nanocomposites in the controlled release of doxorubicin (DOXO), a potent anticancer drug. The strength of the electrostatic interaction between the protonated nitrogen of the DOXO molecule and the ionized carboxylic groups of the hydrogel allowed effective control of the drug release rate in saline solutions. The embedded magnetic nanoparticles were an additional remote control of the drug release under the stimulus of an appropriate external alternating magnetic field (AMF). Data showed that the controlled release of DOXO proceeded for months and followed a diffusion-controlled release mechanism, while maintaining the amount of released drug within acceptable therapeutic windows. The amount of the released DOXO was found in all cases substantially higher than the "control" because the application of the AMF augments in stimulating the nanoparticles within the DOXO-loaded hydrogel. In vitro experiments have shown that the released DOXO is able to induce cell death to cervix adenocarcinoma cells (HeLa cells).
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy. Electronic address: mario.casolaro@unisi.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Casolaro
authors.affiliation: Graduate Student in Psychiatry at the University of Siena, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Casolaro
authors.affiliation: Department of Physical Sciences, Earth and Environmental, University of Siena, Siena, Italy.
authors.forename: Severino
authors.initials: S
authors.lastname: Bottari
authors.affiliation: Istituto Toscano Tumori (ITT), Firenze, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Del Bello
authors.affiliation: Istituto Toscano Tumori (ITT), Firenze, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Maellaro
authors.affiliation: Department of Chemistry, University of Crete, Heraklion, Greece.
authors.forename: Konstantinos D
authors.initials: KD
authors.lastname: Demadis
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D020100:Hydrogels; D066298:In Vitro Techniques; D008280:Magnetics; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000596:Amino Acids; D000903:Antibiotics, Antineoplastic; D020100:Hydrogels; D004317:Doxorubicin
keywords: Alternating magnetic field; Basicity constants; Doxorubicin release; HeLa cells; Magnetic nanoparticles; Stimuli-responsive hydrogels