Carbohydrate Polymers 152 (2016) 306–316 Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol Dual crosslinked iminoboronate-chitosan hydrogels with strong antifungal activity against Candida planktonic yeasts and biofilms Daniela Ailincai a , Luminita Marin a,∗ , Simona Morariu a , Mihai Mares b , Andra-Cristina Bostanaru b , Mariana Pinteala a , Bogdan C. Simionescu a,c , Mihai Barboiu a,d a “Petru Poni” Institute of Macromolecular Chemistry of Romanian Academy, 41A, Aleea Gr. Ghica Voda, Iasi, Romania b “Ion Ionescu de la Brad” University, Laboratory of Antimicrobial Chemotherapy, 8, Aleea Sadoveanu, Iasi, Romania c “Gheorghe Asachi” Technical University of Iasi, 73, Bd. Dimitrie Mangeron, Iasi, Romania d Institut Européen des Membranes, F-34095, Place Eugène Bataillon, Montpellier, France a r t i c l e i n f o Article history: Received 4 May 2016 Received in revised form 29 June 2016 Accepted 2 July 2016 Available online 4 July 2016 Keywords: Hydrogels Iminoboronate Chitosan Supramolecular Antifungal Rheology a b s t r a c t Chitosan based hydrogels are a class of cross-linked materials intensely studied for their biomedical, industrial and environmental application, but their biomedical use is limited because of the toxicity of different organic crosslinkers. To overcome this disadvantage, a new strategy to produce supramolecular chitosan hydrogels using low molecular weight compounds able to form covalent linkages and H-bonds to give a dual crosslinking is proposed. For this purpose we used 2-formylphenylboronic acid, which brings the advantage of imine stabilization via iminoboronate formation and potential antifungal activity due to the presence of boric acid residue. FTIR and NMR spectroscopy indicated that the gelling process took place by chemo-physical crosslinking forming a dual iminoboronate-chitosan network. Further, X- ray diffraction demonstrated a three-dimensional nanostructuring of the iminoboronate network with consequences on the micrometer-scale morphology and on the improvement of mechanical properties, as demonstrated by SEM and rheological investigation. The hydrogels proved strong antifungal activity against Candida planktonic yeasts and biofilms, promising to be a friendly treatment of the recurrent vulvovaginitis infections. © 2016 Elsevier Ltd. All rights reserved. 1. Introduction Hydrogels are three-dimensional polymeric networks which are able to hold a large amount of water or biological fluids, with applicability in a high number of biomedical, industrial and envi- ronmental purposes starting with drug delivery, wound dressing, soft contact lenses or diapers, as well as in restorative dentistry, tissue engineering, water waste treatment and soil conditioning (Buenger, Topuz, & Groll, 2012; Chawla, Ranjan Srivastava, Pandey, & Chawla, 2014; Ullah et al., 2015). Many polymers proved the abil- ity to form hydrogels, in the presence or absence of a crosslinking agent (Palumbo et al., 2015). Among them, chitosan, the second most abundant natural polymer, is recognised as an excellent option due to its rich therapeutic properties: biocompatibility and biodegradability, hemostatic, hypolipidemic, hypoglycemic, anti- tumoral, antimicrobial and fungicidal activity – to mention only ∗ Corresponding author. E-mail addresses: lmarin@icmpp.ro, lmarin2011973@yahoo.com (L. Marin). some (Ravi Kumar, Muzzarelli, Muzzarelli, Sashiwa, & Domb, 2004; Muzzarelli et al., 1994 Muzzarelli, Ilari, Xia, Pinotti, & Tomasetti, 1994). Chitosan based hydrogels can be obtained by either phys- ical or chemical crosslinking. The physically crosslinked chitosan hydrogels present the advantage of being temperature respon- sive, but their application is limited due to their weak mechanical properties and uncontrolled dissolution (Bhattarai, Gunn, & Zhang, 2010). The chemically crosslinked chitosan hydrogels show slower degradability and possibility to control their pore size being recom- mended for in vivo long-term applications (Beauchamp, St Clair, Fennell, Clarke, & Morgan, 1992). Some attempts to combine the two crosslinking ways resulted in dual-network hydrogels with improved mechanical properties, promising to be a reliable route to high performance materials (Bai et al., 2016; Fajardo, Favaro, Rubira, & Muniz, 2013). Since chitosan is a polysaccharide which contains functional amine groups, the primary pathway of its crosslinking is the acid condensation with dialdehydes, especially glutaraldehyde, forming imine bonds. Due to the reversibility of the imine bond formation, the obtained hydrogels have the advantage of being pH-responsive http://dx.doi.org/10.1016/j.carbpol.2016.07.007 0144-8617/© 2016 Elsevier Ltd. All rights reserved.