ORIGINAL PAPER Synthesis and characterization of a novel pH-responsive nanocomposite hydrogel based on chitosan for targeted drug release Mehran Kurdtabar 1 & Roya Nourani Koutenaee 1 & Ghasem Rezanejade Bardajee 2 Received: 15 May 2017 /Accepted: 7 March 2018 # Springer Science+Business Media B.V., part of Springer Nature 2018 Abstract Over the last decade, nanocomposite hydrogels have been provided a new approach for the biomedical field. In this work, a novel pH-responsive nanocomposite hydrogel was fabricated using simultaneous in situ formation of magnetite iron oxide nanopar- ticles and hydrogel networks of poly(acrylic acid) grafted onto chitosan. The effects of various types of precursor molecules, pH, salt, and loading pressure were examined on the swelling properties of resulting nanocomposite hydrogels. The synthesized nanocomposite hydrogel was well characterized using different instruments. In vitro drug releasing behavior of doxorubicin was studied at pH 5.4 and 7.4. The drug release mechanism was investigated through different kinetic models. These experimental results open a new opportunity to make pH-responsive nanocomposite hydrogel devices for controlled delivery of drug. Keywords Chitosan . Magnetite iron oxide nanoparticle . Drug delivery . Nanocomposite hydrogel Introduction Hydrogels are hydrophilic three-dimensional polymeric net- works with high ability to swell in the presence of aqueous or biological solution [1–3]. Despite, they are remaining insolu- ble in these solutions due to their matrix structure [4, 5]. They are formed by physical or chemical crosslinking of synthetic polymers (i.e. poly(amidoamine), poly(acryl amide), poly(vi- nyl alcohol), poly (acrylic acid) (PAA), and poly (N-isopropyl acrylamide)) or natural polymers (i.e. cellulose, alginate, gel- atin, carrageenan, chitosan (CS), and their derivatives) [1–10]. Among them, CS has drawn a considerable attention for the preparation of bio-hydrogel due to their non-toxicity, non-im- munogenicity, biocompatibility, and biodegradability [11]. CS is a linear antimicrobial polysaccharide consisting of N- acetyl-D-glucosamine and D-glucosamine moieties connected by β-1, 4-glycosydic bonds [12]. It is extracted from shells of crustacean (i.e. crabs and shrimps) or is separated from the cell walls of fungi [10]. Hydrogels based CS have been developed as a promising vehicle for drug delivery due to their reactive groups such as OH and NH 2 [11, 12]. These groups possesses excellent inter- or intramolecular hydrogen and imine bonding with drugs and highly important to targeted drug release [11, 12]. In addition to these characteristics, entrapment of drugs into these polyaminosaccharide hydrogels can protect drugs from degradation in many physiological conditions particular- ly gastric acid [13]. However, poor mechanical stability and partial stimuli responsive ability may limit their functionality [ 10 – 13 ]. In order to overcome these disadvantages, nanoparticeles especially magnetite iron oxide nanoparticles (MIONs) were embedded within the 3D hydrogel networks. MIONs have received considerable attention for biomedi- cal applications owing to their size dependent remarkable property, high degree of biocompatibility, and safety [14–18]. Three approaches have been investigated to fabricate MIONs nanocomposite hydrogels. In the first method, MIONs and hydrogel were synthesized separately and then mix [14]. In the second method, MIONs were prepared in pre-synthesized hydrogel [15]. In the third method, MIONs and hydrogel were formed simultaneously in the reaction sys- tem by mixing their solutions [16]. Comparing these methods showed that the third method was highly proper due to prevent the agglomeration of MIONs [16, 17]. Moreover, it was * Mehran Kurdtabar m.kurdtabar@kiau.ac.ir * Ghasem Rezanejade Bardajee rezanejad@pnu.ac.ir 1 Department of Chemistry, Karaj Branch, Islamic Azad University, P.O. Box: 31485-313, Karaj, Iran 2 Department of Chemistry, Payame Noor University, BOX 19395-3697, Tehran, PO, Iran Journal of Polymer Research (2018) 25:119 https://doi.org/10.1007/s10965-018-1499-1