N-isopropylacrylamide-based fine-dispersed thermosensitive ferrogels obtained via in-situ technique O. Korotych a, ⁎, Yu. Samchenko a , I. Boldeskul a , Z. Ulberg a , N. Zholobak b , L. Sukhodub c a Ovcharenko Institute of Biocolloid Chemistry, National Academy of Sciences of Ukraine, Vernadskogo Blvd. 42, Kyiv, 03680, Ukraine b Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, Zabolotnogo St. 154, Kyiv, D0368, Ukraine c Sumy State University, Medical Institute, Ministry of Education and Science, Youth and Sport of Ukraine, R. Korsakova Str. 2, Sumy, 40007, Ukraine abstract article info Article history: Received 19 June 2012 Received in revised form 7 September 2012 Accepted 12 November 2012 Available online 21 November 2012 Keywords: Ferrogels Fine-dispersed hydrogels Nanoreactors Magnetite Hyperthermia Cytotoxicity Thermosensitive hydrogels with magnetic properties (ferrogels) are very promising for medical application, first of all, for the design of targeted delivery systems with controlled release of drugs and for magnetic hyperthermia and chemotherapy treatment of cancer. These magnetic hydrogels could be obtained using diverse techniques: ex- and in-situ syntheses. The present work is devoted to the study of magnetite (Fe 3 O 4 ) formation inside the nanoreactors of (co)polymeric hydrogels. Polymeric templates (hydrogel films and fine-dispersed hydrogels) used for obtaining ferrogels were based on acrylic monomers: thermosensitive N-isopropylacrylamide, and hydrophilic acrylamide. Covalent cross-linking was accomplished using bifunc- tional monomer N,N′-methylenebisacrylamide. Influence of hydrophilic–lipophilic balance of polymeric templates and concentration of iron cations on the magnetite formation were investigated along with the development of ferrogel preparation technique. Cytotoxicity, physical and chemical properties of obtained magnetic hydrogels have been studied in this work. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Polymeric hydrogels are three-dimensional high-molecular net- works containing physically or chemically cross-linked (co)polymeric chains and water. Due to their high biocompatibility and the ability to incorporate drugs into their composition, the hydrogels are widely used in medicine [1], pharmacology, and biology to develop various biomaterials, such as implants, soft contact lenses, wound coatings, cell carriers, drug delivery systems (e.g. that of heparin) [2], etc. Hydrogels are most widely used in regenerative medicine [3] as tissue barriers, bioadhesives, and drug depots, to deliver bioactive agents to boost natural regeneration processes, as well as for the encapsulation and cell delivery. Lately, researchers pay more attention to the so called “smart” polymers and hydrogels whose physical and chemical parameters can dramatically and purposefully change in response to even the slightest changes in the environment. The factors causing such changes are both of physical (temperature [4], light [5], electrical [6] and mag- netic [7] fields) and chemical (pH [8], ionic strength) nature. The poly- meric systems sensitive to temperature are widely studied and appear promising. They are characterized by the presence of upper and/or lower critical solution temperatures (UCST and/or LCST) at which phase transition occurs in the system. Negatively thermosensitive systems are characterized by the presence of LCST, positively—UCST. Swelling of the negatively thermosensitive hydrogels decreases with temperature rise, and the system exists in the collapsed state at temperatures higher than LCST, while positively thermosensitive hydrogels behave oppositely. The most familiar representatives of the negatively thermosensitive systems are alkyl-derivatives of acryl- amide, N-isopropylacrylamide (NIPAAm) and N,N-diethylacrylamide [9], which are studied due to their promising properties for medical application, since the systems have phase transition temperature close to the temperature of human body. The phase transition in polymeric hydrogels and solutions based on NIPAAm is connected with the transition between two conformation structures of the polymer side groups [10]: one of the conformations (cyclic) exists in the hydrated state (at the temperatures lower than LCST), while the other conformation is dehydrated (at the temperatures higher than LCST). With the increase of temperature hydrophobic inter- action increases and thermoinduced molecular vibrations result in the breaking of H-bonds within the cyclic conformation, followed by the dehydration of isopropyl groups and aggregation of hydrophobic fragments. It results in the system transition from the swollen to the collapsed state. LCST of polymeric systems based on NIPAAm is in the range of 32–34 °C and slightly different from the temperature of human body. Materials Science and Engineering C 33 (2013) 892–900 ⁎ Corresponding author. E-mail addresses: korotych.elena@gmail.com (O. Korotych), yu1sam@yahoo.com (Y. Samchenko). 0928-4931/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.msec.2012.11.017 Contents lists available at SciVerse ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec