ORIGINAL PAPER Development of pH-sensitive and antibacterial gelatin/citric acid/Ag nanocomposite hydrogels with potential for biomedical applications Nima Shafagh 1 & Mohammad Sabzi 1 & Mohammad Javad Afshari 1 Received: 25 May 2018 /Accepted: 14 November 2018 # Springer Nature B.V. 2018 Abstract This work aimed to prepare pH-sensitive and antibacterial drug releasing systems through a completely green route. To achieve this, the gelatin natural biopolymer was crosslinked with citric acid in the presence of Ag nanoparticles (NPs). Interestingly, Ag NPs formation and gelatin crosslinking were simultaneously occurred during annealing of samples without need for any toxic chemicals, which were confirmed by FTIR, UV-vis spectra, SEM and TEM observations. In addition, potential of the citric acid crosslinked-gelatin/Ag nanocomposite hydrogels was successfully explored for drug delivery applications using cefixime as a model drug. It was found that these hydrogels have pH-dependent swelling and drug release behavior with higher drug release at pH 7.4 compared to pH 1.2. Also, an antibacterial effect against the E. coli and S. aureus microorganisms was achieved by incorporation of Ag NPs into hydrogels. These hydrogels can be considered as stimuli responsive materials for oral drug delivery and wound dressing applications. Keywords Gelatin . Citric acid . Ag nanoparticles . Green crosslinker . Drug delivery . Antibacterial Introduction In recent years, there has been a significant interest in the development of novel drug delivery systems using functional polymers [1–4]. Among the potential drug carrier systems, drug delivery systems based on gelatin are particularly inter- esting [5–8]. Gelatin is a denatured protein, which is mainly produced from collagen by alkaline and acid hydrolysis. Due to its high availability and inexpensiveness, high biocompat- ibility and biodegradability, it has a long history of safe use in pharmaceuticals, cosmetics, and food products [9–11]. It is a polyampholyte possessing both anionic and cationic groups along with hydrophobic moieties. The functional groups on the molecular chains of gelatin are accessible for various chemical modifications, which can be especially useful in de- veloping targeted drug delivery systems [12–15]. However, neat gelatin dissolves easily in water and has low stability in fluids. Therefore, epichlorohydrin and glutaraldehyde have been used as crosslinkers for gelatin-based biomaterials [16–18]. However, their high toxic nature may limit their ap- plications for many biomedical and food contact packaging applications [19, 20]. Therefore, the use of non-toxic and green crosslinkers such as genipin [21], carbodiimide (CDI) [22], glyoxal [23] or β-cyclodextrin [24] was emerged as an alternative. Citric acid (CA) with three carboxyl groups exists widely in citrus fruits and pineapples, where it is the main organic acid. CA is a non-toxic, inexpensive food additive, which has been used as a cross-linking agent to improve properties of some biopolymers such as starch [25, 26], PVA [27], PVA/ xylan [28] and tragacanth gum [29]. Recently, Uranga et al. [30] have developed citric acid-crosslinked fish gelatin films with the potential for packaging applications. They have found that the presence of citric acid in the films caused no change in color, improved light barrier properties and enhanced mechanical properties. Furthermore, Jiang et al have fabricated citric acid-cross linked gelatin fibrous scaf- folds to mimic the 3D structure of the extracellular matrix with applications in soft tissue repair [31]. Also, in other works [32, 33], citric acid-cross linked gelatin matrices were developed for biomedical applications due to their endothelialization and antithrombogenic properties, and controlled drug release behavior. * Mohammad Sabzi m.sabzi@maragheh.ac.ir 1 Department of Chemical Engineering, Faculty of Engineering, University of Maragheh, Maragheh 55181-83111, Iran Journal of Polymer Research (2018) 25:259 https://doi.org/10.1007/s10965-018-1661-9