Roxithromycin and rhEGF Co-loaded Reactive Oxygen Species Responsive Nanoparticles for Accelerating Wound Healing

Background: Bacterial infection can delay wound healing and is therefore a major threat to public health. Although various strategies have been developed to treat bacterial infections, antibiotics remain the best option to combat infections. The inclusion of growth factors in the treatment approach can also accelerate wound healing. The co-delivery of antibiotics and growth factors for the combined treatment of wounds needs further investigation.Objective: Here we aimed to develop antibiotic and growth factor co-loaded nanoparticles (NPs) to treat Staphylococcus aureus-infected wounds.Methods: By using our previously prepared reactive oxygen species-responsive material (Oxi-alpha CD), roxithromycin (ROX)-loaded NPs (ROX/Oxi-alpha CD NPs) and recombinant human epidermal growth factor (rhEGF)/ROX co-loaded NPs (rhEGF/ROX/Oxi-alpha CD NPs) were successfully fabricated. The in vivo efficacy of this prepared nanomedicine was evaluated in mice with S. aureus-infected wounds.Results: ROX/Oxi-alpha CD NPs and rhEGF/ROX/Oxi-alpha CD NPs had a spherical structure and their particle sizes were 164 +/- 5 nm and 190 +/- 8 nm, respectively. The in vitro antibacterial experiments showed that ROX/Oxi-alpha CD NPs had a lower minimum inhibitory concentration than ROX. The in vivo animal experiments demonstrated that rhEGF/ROX/Oxi-alpha CD NPs could significantly accelerate the healing of S. aureus-infected wounds as compared to the free ROX drug and ROX/Oxi-alpha CD NPs (P < 0.05).Conclusion: ROX and rhEGF co-loaded NPs can effectively eliminate bacteria in wounds and accelerate wound healing. Our present work could provide a new strategy to combat bacteria-infected wounds.