Insights and relative effect of aspirin, naproxen and ibuprofen containing hydrogels: From design to performance as a functional dual capacity restorative material and build in free radical defense: <i>In-vitro</i> studies

Restorative materials in the new era aim to be “bio-active” and long-lasting. It has been suggested that the anti-inflammatory activity of some non-steroidal anti-inflammatory drugs (NSAIDs) may be partly due to their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as to inhibit the respiratory burst of neutrophils triggered by various activating agents. As a part of our continuous interest of developing functional dual action restorative materials capable of being “bio-active” and long-lasting, we design and evaluate novel chitosan hydrogels containing krill oil (antioxidant containing material), naproxen, ibuprofen (non steroidal anti-inflammatory medication), aspirin (pain relieve medication and free radical scavengers) and combinations thereof (chitosan-H-krill oil, chitosan-H-krill oil-aspirin and chitosan-H-naproxen, chitosan-H-naproxen-krill oil, chitosan-H-krill oil-ibuprofen and chitosan-H-ibuprofen) as functional additive prototypes for further development of “dual function restorative materials”; secondly, determine their effect on the dentin bond strength of a composite and thirdly, evaluate the capability of newly designed hydrogels to play an integral role of “build in” free radical defense mechanism by using BSA solubility as a “molecular prototype” of the site of free radical attack in vitro. Materials and Methods: The above mentioned hydrogels were prepared by dispersion of the corresponding component in glycerol and acetic acid with the addition of chitosan gelling agent. The surface morphology (SEM), release behaviors (physiological pH and also in acidic conditions), stability of the therapeutic agent-antioxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were also evaluated. Results: The release of aspirin, ibuprofen and naproxen confers the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Neither the release of aspirin, ibuprofen or naproxen nor the antioxidant stability was affected by storage over a 6- month period. The hydrogel formulations have a uniform distribution of drug content, homogenous texture and yellow color (SEM study). All chitosan dentin treated hydrogels gave significantly (P P in vitro conditions. Conclusion: The added benefits of the chitosan treated hydrogels involved positive influence on the aspirin, ibuprofen and naproxen release, increased dentin bond strength as well as demonstrated in vitro “build in” free radical defense mechanism, therefore acting as a “proof of concept” for the functional multi-dimentional restorative materials with the build in free radical defense mechanism.