PVA/Dextran hydrogel patches as delivery system of antioxidant astaxanthin: A cardiovascular approach

After myocardial infarction, the heart's mechanical properties and its intrinsic capability to recover are compromised. To improve this recovery, several groups have developed cardiac patches based on different biomaterials strategies. Here, we developed polyvinylalcohol/dextran (PVA/Dex) elastic hydrogel patches, obtained through the freeze thawing (FT) process, with the aim to deliver locally a potent natural antioxidant molecule, astaxanthin, and to assist the heart's response against the generated myofibril stress. Extensive rheological and dynamo-mechanical characterization of the effect of the PVA molecular weight, number of freeze-thawing cycles and Dex addition on the mechanical properties of the resulting hydrogels, were carried out. Hydrogel systems based on PVA 145 kDa and PVA 47 kDa blended with Dex 40 kDa, were chosen as the most promising candidates for this application. In order to improve astaxanthin solubility, an inclusion system using hydroxypropyl-β-cyclodextrin was prepared. This system was posteriorly loaded within the PVA/Dex hydrogels. PVA145/Dex 1FT and PVA47/Dex 3FT showed the best rheological and mechanical properties when compared to the other studied systems; environmental scanning electron microscope and confocal imaging evidenced a porous structure of the hydrogels allowing astaxanthin release. In vitro cellular behavior was analyzed after 24 h of contact with astaxanthin-loaded hydrogels. In vivo subcutaneous biocompatibility was performed in rats using PVA145/Dex 1FT, as the best compromise between mechanical support and astaxanthin delivery. Finally, ex vivo and in vivo experiments showed good mechanical and compatibility properties of this hydrogel. The obtained results showed that the studied materials have a potential to be used as myocardial patches to assist infarcted heart mechanical function and to reduce oxidative stress by the in situ release of astaxanthin.