Multi-functional Microneedle Patches for Chronic Wound Infections

Abstract

Bacterial infections can persist as biofilms in wounds, exacerbating infection and potentially causing it to become chronic. Biofilms are difficult to treat because of their robust protective structure that limits antibiotic delivery, while their microenvironment can promotes the spread of antibiotic resistance. Because antibiotics often fail to eradicate established biofilms, removal typically requires surgical debridement, which is costly, time-consuming, and invasive. New treatment strategies are therefore needed to effectively disrupt established biofilms, kill planktonic bacteria, and enable minimally invasive drug delivery. Microneedle patches (MNs) are promising drug delivery systems due to their biocompatibility, tunable mechanical properties, and swelling capacity. Loaded with therapeutics, MNs combine needle penetration with swelling to release of therapeutics deeper into infected tissue. This study assesses the therapeutic effect of two MN designs, NaBIL@MN and MV-ZnO@DMN, on methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Both MNs were successfully fabricated with therapeutic incorporation, sufficient thermal stability and mechanical strength for skin penetration. The MNs showed two distinct hydration behaviours. NaBIL@MN demonstrated swelling behaviour with potential for controlled drug release, while MV-ZnO@DMN rapidly dissolved, likely resulting in burst release. Biological testing demonstrated antibiofilm activity of membrane vesicles (MVs) against MRSA both free form and loaded into the DMN system. ZnO nanoparticles (ZnO NPs) exhibited a minimum inhibitory concentration (MIC) of 100 μg/ml against MRSA, but were cytotoxic at concentrations above 25 μg/ml. Consequently, although MV-ZnO@DMN showed antibiofilm activity, its antimicrobial effect was insufficient to kill bacteria remaining in the biofilm. NaBIL@MN prevented biofilm formation and showed potential dispersive activity against mature biofilms. However, despite significant antimicrobial activity against planktonic MRSA, it did not significantly reduce the viability or growth of bacteria remaining in the biofilm after dispersion. Furthermore, although NaBIL@MN showed clinically acceptable cell viability above 70 %, compromised cell morphology and cell number, together with hemolytic activity exceeding clinical standards, suggest limited biocompatibility. Nevertheless, these findings demonstrate the potential of NaBIL@MN and MV-ZnO@DMN as drug delivery systems against MRSA biofilms while highlighting the challenge of balancing antimicrobial efficacy and cytocompatibility.