Transdermal delivery of antibacterial peptides in the management of methicillin-resistant Staphylococcus aureus.

Bacterial antimicrobial resistance (AMR) is of major public concern around the globe that arises when bacteria which earlier responded to the antibiotic therapy no longer respond to the same therapy and become resistant. The AMR has emerged due to the antibiotic abuse resulting in the development of multidrug-resistant (MDR) bacteria including methicillin-resistant Staphylococcus aureus (MRSA). The conventional antibiotics including vancomycin have nowadays become ineffective due to the gradual evolution and adaptation of bacteria to the surrounding environment. Antimicrobial peptides (AMPs) have emerged as an effective therapeutic option for the treatment of MRSA-induced skin and soft tissue infections (SSTIs). They offer broad-spectrum antibacterial activity with lower probability of drug resistance development. However, these AMPs face limitations such as proteolytic degradation, poor bioavailability, and potential cytotoxicity limiting their efficacy in clinical settings. Transdermal drug delivery platforms, including microneedles (MNs) coupled with the nano-formulations, have been developed to improve the AMP stability, bioavailability, and targeted release to avoid off-target cytotoxicity. Innovative strategies including Janus-type antibacterial dressings, bioresponsive MNs, and metal-organic frameworks (MOFs)-based nanocarriers have shown favorable results against the MRSA-induced skin infection. Numerous naturally occurring and synthetic antibacterial biopeptides and a Food and Drug Administration-approved glycopeptide, vancomycin, exhibited improved biofilm penetration and therapeutic efficacy when combined with smart MNs and nanosystems. Despite these improvements, challenges associated with AMP stability, cytotoxicity, and manufacturing costs still remain that limit its clinical translation. This review discussed the various MN-assisted deliveries of AMPs and associated challenges for the treatment of MRSA infections.