A Bioadhesive Nanoparticle-Hydrogel Hybrid System for Localized Antimicrobial Drug Delivery

Effective antibacterial treatment at the infection site associated with high shear forces remains challenging, owing largely to the lack of durably adhesive and safe delivery platforms that can enable localized antibiotic accumulation against bacterial colonization. Inspired by delivery systems mimicking marine mussels for adhesion, herein, we developed a bioadhesive nanoparticle-hydrogel hybrid (NP-gel) to enhance localized antimicrobial drug delivery. Antibiotics were loaded into polymeric nanoparticles and then embedded into a 3D hydrogel network that confers adhesion to biological surfaces. The combination of two distinct delivery platforms, namely, nanoparticles and hydrogel, allows the hydrogel network properties to be independently tailored for adhesion while maintaining controlled and prolonged antibiotic release profile from the nanoparticles. The bioadhesive NP-gel developed here showed superior adhesion and antibiotic retention under high shear stress on a bacterial film, a mammalian cell monolayer, and mouse skin tissue. Under a flow environment, the NP-gel inhibited the formation of an Escherichia coli bacterial film. When applied on mouse skin tissue for 7 consecutive days, the NP-gel did not generate any observable skin reaction or toxicity, implying its potential as a safe and effective local delivery platform against microbial infections.