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Skin infections caused by multidrug-resistant bacteria are an increasing public health concern, requiring therapeutic approaches. Antimicrobial peptides (AMPs) have been studied as alternatives to conventional antibiotics due to their broad-spectrum activity and lower risk of inducing resistance. However, their clinical application remains limited due to enzymatic instability, rapid clearance, and potential toxicity. Lipid nanoparticles (LNPs) have emerged as a promising strategy to protect and deliver AMPs in a controlled manner, enhancing their efficacy while reducing side effects. This review explores how AMP encapsulation within LNPs can improve stability, prolong antimicrobial activity, and optimize skin penetration. Despite recent advances, challenges, such as scalability, regulatory approval, and clinical application, must still be addressed to bring this approach into widespread use for skin infection treatment. This review explores the synergy between AMPs and LNPs, focusing on their mechanisms of action, in vitro and in vivo efficacy, and controlled drug release strategies. We highlight the advantages of LNP encapsulation, including increased bioavailability, prolonged antimicrobial activity, and reduced systemic toxicity. Various LNP types, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), are discussed in relation to their structural properties and impact on AMP delivery. Despite these advancements, challenges remain in optimizing formulation scalability, regulatory approval, and clinical translation. Future research should focus on hybrid delivery platforms, stimuli-responsive systems, and large-scale production techniques to enhance AMP-based nanotherapies. Integrating LNPs into AMP therapeutics represents a transformative approach to combating antibiotic resistance and improving skin infection management.
Buccini et al. (Sat,) studied this question.