Nanosystems for delivery of indolicidin peptide

The emergence of multidrug-resistant pathogens has necessitated the search for novel therapeutic alternatives such as antimicrobial peptides (AMPs). Indolicidin (Ind) represents a highly promising candidate owing to its broad-spectrum activity and multimodal mechanisms; however, its clinical translation is limited by rapid proteolytic degradation and intrinsic host cytotoxicity. To overcome these pharmacological bottlenecks, this review places nanocarrier based delivery of Ind at its analytical center, rigorously evaluating the integration of Ind into nanoscale delivery systems as a transformative therapeutic strategy. We critically analyze how diverse organic and inorganic platforms fundamentally reconfigure Ind's mechanism of action, including the bidirectional relationship between nanoparticle-generated ROS and peptide-mediated membrane disruption. Furthermore, we discuss emerging bio-inspired approaches utilizing stimuli-responsive hydrogels, lipid cubic phases, and liposomes for programmed intracellular release. A critical assessment of long-term genotoxicological and ecotoxicological safety profiles is subsequently provided to address mandatory regulatory prerequisites. This integrated analysis establishes a comprehensive mechanistic and translational framework for the rational development of next-generation Ind-based antimicrobial nanomedicines, balancing structural tethering with supramolecular assembly to effectively combat antibiotic-resistant infections.