Alfei Silvana, Zuccari Guendalina, Caviglia Debora, Brullo Chiara
Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy.
Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, I-16132 Genova, Italy.
Nanomaterials (Basel). 2022 Apr 5;12(7):1215. doi: 10.3390/nano12071215.
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.
一种吡唑衍生物（CB1）先前以二甲基亚砜作为给药介质，在体内评估了其各种药理活性（抗菌作用除外），主要是因为它不溶于水。考虑到全球对新型抗菌剂的需求，CB1作为满足这一需求的候选物引起了我们的关注，主要是因为其结构中的仲胺基团使其有可能获得盐酸盐（CB1H），从而轻松解决其水溶性缺点。在对革兰氏阴性菌和革兰氏阳性菌的初步微生物学研究中，CB1H对革兰氏阳性菌的多重耐药分离株显示出较弱的抗菌作用，但仍优于常用的现有抗生素。因此，为了提高这种活性并将CB1H的抗菌谱扩展到革兰氏阴性病原体，在这项首次研究中，使用我们先前开发的具有强大广谱杀菌活性的阳离子共聚物（P7）将CB1策略性地制备成纳米颗粒。采用纳米沉淀法制备了负载CB1H的聚合物纳米颗粒（CB1H-P7 NPs），通过衰减全反射-傅里叶变换红外光谱（ATR-FTIR）对其进行分析以确认成功负载。此外，还对CB1H-P7 NPs的形态、尺寸、多分散指数、表面电荷、药物负载率（DL%）、包封率（EE%）以及释放和电位曲线进行了全面表征。
