Electric, pH, and Mechanical Stimuli-Responsive Hydrogels from Methacrylated Pullulan and Carboxymethylated-Methacrylated Xanthan Gum as Drug Carriers

Polyanionic polysaccharide-based hydrogels were developed as multistimuli-responsive drug carriers. Methacrylated pullulan (MP) acted as a thinner and rigidity regulator. Carboxymethylated-methacrylated xanthan gum (CMMXG) provided negative charges, ionic conductivity, and viscoelasticity. The cumulative ciprofloxacin hydrochloride (CPFXH) release mass dropped dramatically, whether the hydrogel was set at the anode or cathode with a potential of 3 V, due to irreversible electrochemical oxidation. Hydrogels with lower drug-loading amounts exhibited higher release efficiency when an electric stimulus was applied in the initial 5 h. A high CPFXH-loading amount led to rapid diffusion and quick electrochemical oxidation. For CMMXG3-MP7.5-CPFXH1680-LAP, the CPFXH release efficiency ratio of 3 to 0 V decreased from 1.33 ± 0.43 to 1.01 ± 0.06 over a duration of 0.5 ∼ 2 h, further indicating that the encouraged release and electrochemical degradation occurred simultaneously. The CPFXH release efficiency in phosphate buffer saline (pH = 7.4) was 1.5 times higher than that in simulated gastric fluid (pH = 1.2), and the CPFXH diffusion coefficient with loading weight was 6 times higher than that without loading, indicating that it was sensitive to pH and compressive force. The hydrogels exhibited electric, pH, and mechanical stimuli-responsiveness due to the presence of charged groups along the chains and viscoelasticity with robustness enough to respond and withstand compressive loading.