Designing biomimetic hydrogels for neuro-therapeutic delivery devices for brain soft tissue injury: integrating antioxidant, cell viability and tissue adhesion properties to enhance neural regeneration via a synergistic approach

Abstract

Recent progress in brain research reflects an exciting interface of technology and biology, leading to the development of effective therapeutic compounds and site specific delivery systems to address complex neurological disorders. These innovative therapies also serve as novel diagnostic and therapeutic platforms for drug delivery (DD) to the brain and soft tissue in the context of brain injury, aiming to enhance drug penetration and targeting while improving efficacy and minimizing systemic toxicity. Hence, the innovative approach of this project lies in the development of a network structure in the form of hydrogels derived from bioactive sulphated polysaccharide & zwitterionic polymers by the copolymerization technique for the delivery of the neuroprotective & neurorestorative (citicoline) compound at the site of nerve injury. The biocompatibility, protein adsorption, antioxidant, mucoadhesion, drug delivery and cell-viability of rhabdomyosarcoma cell properties of hydrogels were analyzed. Hydrogels expressed 165 ± 0.19% cell viability of RD cells and promoted cell adhesion and proliferation, signifying their compatibility with mammalian cells. DPPH assay revealed 39.82 ± 1.65% free radical scavenging ability of the materials, highlighting their strong intrinsic antioxidant potential for neutralizing oxidative stress at the site of nerve injury. The mucoadhesion of the materials was signified from a force of 75 ± 4.00 mN, desirable for adherence to mucosal surfaces and helps in cell attachment and alignment during the nerve regeneration process. The citicoline anchored brain drug delivery carrier released the drug in simulated brain fluid in a sustained pattern and followed the non-Fickian diffusion mechanism. The release profile was best explained by the Hixson–Crowell kinetic model. The materials were also characterized by FESEM, EDAX, AFM, FTIR, ¹³C-NMR & XRD techniques. Overall, the presented synergistic therapy for treatment of brain injury involved the delivery of the bioactive nerve regenerating agent from functional materials. It will not only deliver therapeutic molecules to nerve injuries but its inherent antioxidant, haemostatic & non-cytotoxic nature with cell viability properties may also contribute to enhancing the nerve repair process of brain injury.