Potent Broad-Spectrum Antibacterial/Bactericidal Nanoparticles by Complexing a Weakly Active Pyrazole Hydrochloride with a Cationic Copolymer as Enhancer Agent

Even though the pyrazole nucleus is known to have antibacterial properties, a pyrazole derivative (CB1) was previously evaluated in vivo for various pharmacological activities, except for antimicrobial effects, using DMSO as administration medium, 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. Once prepared CB1H , its antibacterial activity was screened on Gram-negative and Gram-positive bacteria, observing 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, CB1H was strategically formulated in nanoparticles using a cationic copolymer (P7), previously prepared by us and possessing potent broad-spectrum bactericidal activity. Using the nanoprecipitation method, CB1H-loaded polymer nanoparticles (CB1H-P7 NPs) were obtained and analysed by ATR-FTIR spectroscopy to confirm the successful loading. Additionally, CB1H-P7 NPs were fully characterized in terms of morphology, size, polydispersity index, surface charge, DL%, and EE%, as well as release and potentiometric profiles.