title: Tunable drug-loading capability of chitosan hydrogels with varied network architectures.
abstract: Advanced bioactive systems with defined macroscopic properties and spatio-temporal sequestration of extracellular biomacromolecules are highly desirable for next generation therapeutics. Here, chitosan (CT) hydrogels were prepared with neutral or negatively charged cross-linkers in order to promote selective electrostatic complexation with charged drugs. CT was functionalized with varied dicarboxylic acids, such as tartaric acid, poly(ethylene glycol) bis(carboxymethyl) ether, 1,4-phenylenediacetic acid and 5-sulfoisophthalic acid monosodium salt (PhS), whereby PhS was hypothesized to act as a simple mimetic of heparin. Attenuated total reflectance Fourier transform infrared spectroscopy showed the presence of CO amide I, N-H amide II and CO ester bands, providing evidence of covalent network formation. The cross-linker content was reversely quantified by proton nuclear magnetic resonance on partially degraded network oligomers, so that 18 mol.% PhS was exemplarily determined. Swellability (SR: 299 ± 65-1054 ± 121 wt.%), compressibility (E: 2.1 ± 0.9-9.2 ± 2.3 kPa), material morphology and drug-loading capability were successfully adjusted based on the selected network architecture. Here, hydrogel incubation with model drugs of varied electrostatic charge, i.e. allura red (AR, doubly negatively charged), methyl orange (MO, negatively charged) or methylene blue (MB, positively charged), resulted in direct hydrogel-dye electrostatic complexation. Importantly, the cationic compound, MB, showed different incorporation behaviours, depending on the electrostatic character of the selected cross-linker. In light of this tunable drug-loading capability, these CT hydrogels would be highly attractive as drug reservoirs towards e.g. the fabrication of tissue models in vitro.
authors.affiliation: Biomaterials and Tissue Engineering Research Group, School of Dentistry, University of Leeds, Clarendon Way, Leeds LS2 9LU, UK; Nonwovens Research Group, Centre for Technical Textiles, School of Design, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tronci
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Ajiro
authors.affiliation: Nonwovens Research Group, Centre for Technical Textiles, School of Design, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Russell
authors.affiliation: Biomaterials and Tissue Engineering Research Group, School of Dentistry, University of Leeds, Clarendon Way, Leeds LS2 9LU, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wood
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1, Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: akashi@chem.eng.osaka-u.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
mesh_terms: D048271:Chitosan / Q000737:chemistry*; D019245:Compressive Strength; D004337:Drug Carriers / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D055595:Mechanical Phenomena; D008855:Microscopy, Electron, Scanning; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013696:Temperature; D013818:Thermogravimetry
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D048271:Chitosan
keywords: Bioactive hydrogels; Chitosan; Crosslinked network; Drug loading; Sulfonic acid