Preparation and Physicochemical Characterization of Water-Soluble Pyrazole-Based Nanoparticles by Dendrimer Encapsulation of an Insoluble Bioactive Pyrazole Derivative

• Published in: Nanomaterials (Basel, Switzerland) Vol. 11; no. 10; p. 2662
• Main Authors: Alfei, Silvana, Brullo, Chiara, Caviglia, Debora, Zuccari, Guendalina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10-10-2021; MDPI
• Subjects: 2-(4-Bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4); Analgesics; Antibacterial activity; Antiinfectives and antibacterials; Antimicrobial agents; Bacteria; Bacterial infections; Biodegradability; Biodegradation; biphasic release profile; Cancer; Chromatography; Cytotoxicity; Drug resistance; Encapsulation; Entrapment; Ethanol; fourth-generation polyester-based lysine-modified dendrimer; Light scattering; Microscopy; Nanoparticles; Nanotechnology; NMR; Nonsteroidal anti-inflammatory drugs; Nuclear magnetic resonance; Photon correlation spectroscopy; physical encapsulation; Polymers; Potentiometric titration; Pyrazole; Pyrazoles; Solvents; Spectrum analysis; spherical morphology; Titration; Water chemistry; water-soluble BBB4-loaded NPs; United Kingdom > UK; United States > US; Germany; 2-(4-Bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4); first-order kinetics; fourth-generation polyester-based lysine-modified dendrimer; water-soluble BBB4-loaded NPs; physical encapsulation; NMR investigations; biphasic release profile; spherical morphology; high drug loading
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano11102662

2-(4-Bromo-3,5-diphenyl-pyrazol-1-yl)-ethanol (BBB4) was synthetized and successfully evaluated concerning numerous biological activities, except for antimicrobial and cytotoxic effects. Due to the antimicrobial effects possessed by pyrazole nucleus, which have been widely reported, and the worldwide need for new antimicrobial agents, we thought it would be interesting to test BBB4 and to evaluate its possible antibacterial effects. Nevertheless, since it is water-insoluble, the future clinical application of BBB4 will remain utopic unless water-soluble BBB4 formulations are developed. To this end, before implementing biological evaluations, BBB4 was herein re-synthetized and characterized, and a new water-soluble BBB4-based nano-formulation was developed by its physical entrapment in a biodegradable non-cytotoxic cationic dendrimer (G4K), without recovering harmful solvents as DMSO or surfactants. The obtained BBB4 nanoparticles (BBB4-G4K NPs) showed good drug loading (DL%), satisfying encapsulation efficiency (EE%), and a biphasic quantitative release profile governed by first-order kinetics after 24 h. Additionally, BBB4-G4K was characterized by ATR-FTIR spectroscopy, NMR, SEM, dynamic light scattering analysis (DLS), and potentiometric titration experiments. While, before the nanotechnological manipulation, BBB4 was completely water-insoluble, in the form of BBB4-G4K NPs, its water-solubility resulted in being 105-fold higher than that of the pristine form, thus establishing the feasibility of its clinical application.