Bacterial antimicrobial resistance (AMR) refers to the ability of bacteria to survive the effect of antibacterial agents, especially antibiotics through gene mutation. The emergence of bacterial AMR poses a global health threat as estimations suggest that if no effective countermeasures are prompted, the spread of AMR could render many bacterial pathogens far more fatal in the future than they are currently [1,2]. In recent years, bacterial infection has escalated, increasing the use of broad-spectrum antibiotics. Unfortunately, overuse of antibiotics in human medicine coupled with poor antimicrobial stewardship, self-prescription, and inappropriate dosing has led to the emergence of multidrug-resistant (MDR) bacteria [3]. Among these, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus, MDR Pseudomonas aeruginosa (MDR-PA), and MDR-Acinetobacter baumannii (MDR-AB) are some of the most commonly diagnosed MDR bacteria in clinical settings [3, 4, 5]. MRSA is a resistant strain of the Gram-positive bacterium, Staphylococcus aureus, which is known to cause both community and nosocomial skin and soft tissue infections (SSTIs) [6]. These infections are extremely challenging to treat because initially, it displayed resistance against a single class of antibiotics; however, nowadays MRSA exhibits anti-antibiotic resistance rendering most of the conventional antibiotics ineffective including vancomycin [7].Management of MRSA infections becomes even harder because it can establish biofilms that hinder the penetration of antibiotics and present multilevel defense mechanism in contrast to the planktonic cells [8,9]. Hence, the failure of antibiotic therapy against MRSA infections necessitates the development of newer antimicrobial strategies urging researchers and healthcare providers to discover effective alternatives.

Currently, antimicrobial peptides (AMPs) have gained considerable traction due to their effectiveness against MRSA infections [10]. They are now considered a viable alternative to conventional antibiotics owing to their broad-spectrum antimicrobial activity, ability to disrupt bacterial membranes, and lesser probability of resistance development [11, 12, 13]. Unlike conventional antibiotics that interrupt bacterial growth through a single mechanism, AMPs are capable of destroying bacterial pathogens via multiple mechanistic approaches, prominently reducing the occurrence of drug-resistant bacteria [7,11,12]. However, their physicochemical properties, stability issues such as susceptibility to proteolytic or enzymatic degradation, and high systemic toxicities limit their potential application in clinical practices [14, 15, 16]. To circumvent these limitations, and enhance AMP’s effectiveness against MRSA infection and biofilm formation, researchers have scrutinized different biomaterial-based transdermal delivery (TDD) approaches. These TDD systems along with advanced biomaterial-based formulations prevent AMP degradation before its delivery to the targeted site, by bypassing the limitations of oral and parenteral administration [10]. This review focuses on the innovative strategies of transdermal delivery of AMPs for the management of MRSA infections. It highlights the usage of biocompatible carriers, nano-formulations, and advanced biomaterial technologies that ease the delivery of AMPs to the site of action (Figure 1). Additionally, it discusses the remaining challenges in the transdermal delivery of AMPs and prospects to entirely realize their potential in clinical settings.