Release of Bioactive Molecules from Graphene Oxide-Alginate Hybrid Hydrogels: Effect of Crosslinking Method

To investigate the influence of crosslinking methods on the releasing performance of hybrid hydrogels, we synthesized two systems consisting of Graphene oxide (GO) as a functional element and alginate as polymer counterpart by means of ionic gelation (physical method, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>P</mi></msubsup></mrow></semantics></math></inline-formula>) and radical polymerization (chemical method, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>C</mi></msubsup></mrow></semantics></math></inline-formula>). Formulations were optimized to maximize the GO content (2.0 and 1.15% for <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>P</mi></msubsup></mrow></semantics></math></inline-formula> and <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>C</mi></msubsup></mrow></semantics></math></inline-formula>, respectively) and Curcumin (CUR) was loaded as a model drug at 2.5, 5.0, and 7.5% (by weight). The physico-chemical characterization confirmed the homogeneous incorporation of GO within the polymer network and the enhanced thermal stability of hybrid vs. blank hydrogels. The determination of swelling profiles showed a higher swelling degree for <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>C</mi></msubsup></mrow></semantics></math></inline-formula> and a marked pH responsivity due to the COOH functionalities. Moreover, the application of external voltages modified the water affinity of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>C</mi></msubsup></mrow></semantics></math></inline-formula>, while they accelerated the degradation of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>P</mi></msubsup></mrow></semantics></math></inline-formula> due to the disruption of the crosslinking points and the partial dissolution of alginate. The evaluation of release profiles, extensively analysed by the application of semi-empirical mathematical models, showed a sustained release from hybrid hydrogels, and the possibility to modulate the releasing amount and rate by electro-stimulation of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msubsup><mi>H</mi><mrow><mi>A</mi><mo>−</mo><mi>G</mi><mi>O</mi></mrow><mi>C</mi></msubsup></mrow></semantics></math></inline-formula>.