In the last few years, antibiotic resistance and, analogously, anticancer drug resistance have increased considerably, becoming one of the main public health problems. For this reason, it is crucial to find therapeutic strategies able to counteract the onset of multi-drug resistance (MDR). In this review, a critical overview of the innovative tools available today to fight MDR is reported. In this direction, the use of membrane-disruptive peptides/peptidomimetics (MDPs), such as antimicrobial peptides (AMPs), has received particular attention, due to their high selectivity and to their limited side effects. Moreover, similarities between bacteria and cancer cells are herein reported and the hypothesis of the possible use of AMPs also in anticancer therapies is discussed. However, it is important to take into account the limitations that could negatively impact clinical application and, in particular, the need for an efficient delivery system. In this regard, the use of nanoparticles (NPs) is proposed as a potential strategy to improve therapy; moreover, among polymeric NPs, cationic ones are emerging as promising tools able to fight the onset of MDR both in bacteria and in cancer cells.

A pyrazole derivative (CB1) was previously evaluated in vivo for various pharmacological activities (with the exception of antimicrobial effects), using DMSO as the administrative medium, mainly due to its water insolubility. Considering the global necessity for new antimicrobial agents, CB1 attracted our attention as a candidate to meet this need, mainly because the secondary amine group in its structure would make it possible to obtain its hydrochloride salt (CB1H), thus effortlessly solving its water-solubility drawbacks. In preliminary microbiologic investigations on Gram-negative and Gram-positive bacteria, CB1H displayed weak antibacterial effects on MDR isolates of Gram-positive species, nonetheless better than those displayed by the commonly-used available antibiotics. Therefore, aiming at improving such activity and extending the antibacterial spectrum of CB1H to Gram-negative pathogens, in this first work CB1 was strategically formulated in nanoparticles using a cationic copolymer (P7) previously developed by us, possessing potent broad-spectrum bactericidal activity. Using the nanoprecipitation method, CB1H-loaded polymer nanoparticles (CB1H-P7 NPs) were obtained, which were analyzed by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to confirm the successful loading. Additionally, CB1H-P7 NPs were fully characterized in terms of morphology, size, polydispersity indices, surface charge, DL%, and EE%, as well as release and potentiometric profiles.