Introduction: Antimicrobial Peptides (AMPs) are intriguing alternatives to antibiotics for combating Multidrug-Resistant (MDR) pathogens; however, their clinical use is restricted by their rapid clearance, poor tissue penetration, and enzymatic degradation. Methods: We conducted a systematic analysis of lipidic and polymeric nanoparticles for antimicrobial peptide administration, assessing encapsulation efficiency, release kinetics, biocompatibility, and antibacterial activity. In vitro and in vivo investigations, along with patented technology, were evaluated to discern significant advancements and obstacles. Results: In addition to enhancing the bioavailability of AMPs, nanoparticle formulations facilitate targeted delivery to infection sites and reduce off-target toxicity, including against ESKAPE pathogens. Preclinical studies have demonstrated that stimuli-responsive systems enable controlled release, while surface functionalization, including ligand targeting and PEGylation, improves stability and specificity. Regulatory obstacles, such as standardized quality attributes and trial endpoints, persist; however, they are mitigated by global initiatives, such as the World Health Organization's 2024 antimicrobial development initiative. Conclusion: Nanoparticle-driven AMP therapies hold significant promise for treating infectious diseases by effectively addressing delivery challenges. Future initiatives must enhance scalable functionalization and address regulatory challenges to expedite clinical translation for MDR infections.
Kumar et al. (Thu,) studied this question.
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