TiO2@Alginate/Chitosan Core–Shell Nanoparticles in 3D–Printed Hydrogel for the Topical Delivery of Salvadora persica Extract and Neomycin Sulphate

Wound healing is a physiological mechanism performed by the body at the wound site as an attempt to cutout bleeding and microbial infections. Recently, the invention of topical drug delivery systems to assist the wound healing process has grasped the attention of researchers. Here, we report the fabrication, characterization, in vitro and in vivo assessments of a topical natural polymeric 3D-printed hydrogel comprising core-shell titanium dioxide nanoparticles (TiO2 NPs) coated with alginate and chitosan polymers for the delivery of neomycin sulphate antibiotic and Salvadora persica aqueous extract to aid in wound healing in Rattus norvegicus animal model. The synthesized core-shell nanoparticles demonstrated an average particle size of ca. 80 nm, while the hydrothermally synthesized TiO2 NPs showed a mean particle size of ca. 10 nm, as revealed from the dynamic light scattering measurements. In vitro experiments on human skin fibroblasts demonstrated excellent biocompatibility of the nanoparticles under investigation. In addition, both plain and drug-loaded core-shell TiO2 nanoparticles exhibited anti-inflammatory activities via the inhibition of cyclooxygenase isoforms. Moreover, the nanoparticles showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, indicating their excellent antioxidant activity. Furthermore, the proposed drug delivery system exhibited a marked increase in the IL-10 (anti-inflammatory cytokine) and a well-observed decrease in the level of TNF-α (pro-inflammatory cytokines), as revealed from the in vivo study. Monitoring wound area and histopathological changes in the studied animal groups confirmed the ability of the proposed drug-delivery system to assist in complete wound healing within fifteen days.