Antimicrobial peptides (AMPs) are essential elements of thehost defense system. Characterized by heterogenous structures and broad‐spectrumaction, they are promising candidates for combating multidrug resistance. Thecombined use of AMPs with other antimicrobial agents provides a new arsenal ofdrugs with synergistic action, thereby overcoming the drawback of monotherapiesduring infections. AMPs kill microbes via pore formation, thus inhibitingintracellular functions. This mechanism of action by AMPs is an advantage overantibiotics as it hinders the development of drug resistance. The synergisticeffect of AMPs will allow the repurposing of conventional antimicrobials andenhance their clinical outcomes, reduce toxicity, and, most significantly,prevent the development of resistance. In this review, various synergies ofAMPs with antimicrobials and miscellaneous agents are discussed. The effect ofstructural diversity and chemical modification on AMP properties is firstaddressed and then different combinations that can lead to synergistic action,whether this combination is between AMPs and antimicrobials, or AMPs andmiscellaneous compounds, are attended. This review can serve as guidance whenredesigning and repurposing the use of AMPs in combination with other antimicrobialagents for enhanced clinical outcomes.

In this study, chitosan-modified basic amino acid derivatives were explored as novel absorption enhancers and nanocarriers for oral insulin delivery. N-Arginine-chitosan (ACS) and N-histidine-chitosan (HCS) were successfully synthesized, and their polyelectrolyte complexes (PECs) with insulin were formed by the ordinary self-assembly method. The obtained PECs exhibited a spherical morphology with a narrow size of 205–303 nm, positive surface charge (ζ potential + 14– + 27 mV) and encapsulation efficiency of approximately 80%. The electrostatic interactions between chitosan derivatives and insulin were confirmed by molecular modeling simulation. In vitro studies demonstrated that PECs could partially protect insulin from proteolysis and degradation at 50 °C for at least 6 h. Compared with the insulin solution, internalization of PECs into Caco-2 cells was increased by up to 20.7-fold. Moreover, permeability was enhanced as the degrees of substitution of arginine and histidine increased. The PECs had in vivo pharmacological activities of 2.29%–5.39%, with a significant reduction of blood glucose levels in diabetic rats. These results suggested that ACS and HCS PECs hold promising potential for the oral delivery of insulin, peptides and proteins.