Selective delivery of silver nanoparticles for improved treatment of biofilm skin infection using bacteria-responsive microparticles loaded into dissolving microneedles

The treatment of infected chronic wounds has been hampered by development of bacterial biofilms and the low penetration of antibacterial compounds delivered by conventional dosage forms. Numerous bacterial biofilm formers have shown resistance to synthetic antibacterial agents. In this study, we explore the potential of silver nanoparticles (NPs) synthesized using green tea extract as antibiofilm agents against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) biofilms. Due to the toxicity of silver NPs, for the first time, silver NPs were incorporated into bacteria-responsive microparticles (MPs) prepared from poly (Ɛ-caprolactone) decorated with chitosan. The in vitro release of silver NPs from MPs increased up to 9-times in the presence of SA and PA, showing the selectivity of this approach. Incorporation of the MPs into dissolving microneedles (DMNs) could enhance the dermatokinetic profiles of silver NPs compared to DMNs containing silver NPs without MP formulations and conventional cream formulations. Furthermore, 100% of bacterial bioburdens were eradicated on ex vivo biofilm model in rat skin following 60 h of the administration of this system. The findings revealed here confirmed the feasibility of the loading of silver NPs into responsive MPs for improved antibiofilm activities when delivered using DMNs. Following on from these promising results, toxicity and in vivo pharmacodynamic studies should now be carried out in an appropriate model.