Based on the widely reported antimicrobial effects possessed by the pyrazole nucleus and the worldwide need for new antimicrobial agents, we test two home-made pharmacologically active pyrazole derivatives, namely CR232 and BBB4 to evaluate their antibacterial effects. Nevertheless, due to their water-insolubility, the results from microbiologic experiments on CR232 were not clear, and the future clinical application of both compounds would have remained utopic unless first, water-soluble formulations had not been prepared. To this end, before implementing further biological evaluations, BBB4 and CR232 were physically entrapped in biodegradable non-cytotoxic cationic dendrimers containing lysine (K) (namely G4K and G5K), without using harmful solvents as DMSO, or surfactants. The obtained BBB4-loaded and CR232-loaded nanoparticles (BBB4-G4K and CR232-G5K NPs) were water-soluble and showed from good to very high values of drug loading (DL%), and encapsulation efficiency (EE%). Additionally, while a biphasic quantitative release profile governed by first-order kinetics was observed after 24h for BBB4-G4K NPs, a complex but anyway quantitative release profile governed by Weibull kinetics, was observed for CR232-G5K NPs. Both nano-formulations were characterized by ATR-FTIR spectroscopy, also processed by multivariate analyses (MVA), NMR, SEM, dynamic light scattering analysis (DLS), and potentiometric titration experiments. While before the nanotechnological manipulation, BBB4 and CR232 were completely water-insoluble, in the form of BBB4-G4K and CR232-G5K NPs, their water-solubility resulted 105-fold and 2311-fold respectively higher than those of the pristine forms, thus establishing the feasibility of their clinical application. As reported in detail in the poster session, BBB4-G4K NPs demonstrated potent antibacterial effects specifically against Staphylococci including methicillin-resistant strains of Staphylococcus aureus and S. epidermidis, while CR232-G5K NPs proved very potent broad-spectrum bactericidal effects against several strains of several genera of both Gram-positive and Gram-negative species, regardless their resistance pattern.

From Weakly Active Insoluble Pyrazoles Not Clinically Administrable, New Potent Antibacterial Water-Soluble Nanoparticles Using Cationic Dendrimers as Solubilizing Agents

S. Alfei;C. Brullo;A. Spallarossa;G. Zuccari
2022

Abstract

Based on the widely reported antimicrobial effects possessed by the pyrazole nucleus and the worldwide need for new antimicrobial agents, we test two home-made pharmacologically active pyrazole derivatives, namely CR232 and BBB4 to evaluate their antibacterial effects. Nevertheless, due to their water-insolubility, the results from microbiologic experiments on CR232 were not clear, and the future clinical application of both compounds would have remained utopic unless first, water-soluble formulations had not been prepared. To this end, before implementing further biological evaluations, BBB4 and CR232 were physically entrapped in biodegradable non-cytotoxic cationic dendrimers containing lysine (K) (namely G4K and G5K), without using harmful solvents as DMSO, or surfactants. The obtained BBB4-loaded and CR232-loaded nanoparticles (BBB4-G4K and CR232-G5K NPs) were water-soluble and showed from good to very high values of drug loading (DL%), and encapsulation efficiency (EE%). Additionally, while a biphasic quantitative release profile governed by first-order kinetics was observed after 24h for BBB4-G4K NPs, a complex but anyway quantitative release profile governed by Weibull kinetics, was observed for CR232-G5K NPs. Both nano-formulations were characterized by ATR-FTIR spectroscopy, also processed by multivariate analyses (MVA), NMR, SEM, dynamic light scattering analysis (DLS), and potentiometric titration experiments. While before the nanotechnological manipulation, BBB4 and CR232 were completely water-insoluble, in the form of BBB4-G4K and CR232-G5K NPs, their water-solubility resulted 105-fold and 2311-fold respectively higher than those of the pristine forms, thus establishing the feasibility of their clinical application. As reported in detail in the poster session, BBB4-G4K NPs demonstrated potent antibacterial effects specifically against Staphylococci including methicillin-resistant strains of Staphylococcus aureus and S. epidermidis, while CR232-G5K NPs proved very potent broad-spectrum bactericidal effects against several strains of several genera of both Gram-positive and Gram-negative species, regardless their resistance pattern.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11567/1095794
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