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含姜黄素的橄榄油纳米乳:抗多种耐药菌的抗菌剂。

Olive oil nanoemulsion containing curcumin: antimicrobial agent against multidrug-resistant bacteria.

机构信息

Keizo Asami Institute (iLIKA), Federal University of Pernambuco (UFPE), Prof. Moraes Rego Avenue, 1235, Cidade Universitária, CEP, Recife, Pernambuco, 50670-901, Brazil.

University Center UNIFACISA, Manoel Cardoso Palhano, 124-152, Itararé, CEP, Campina Grande, Paraiba, 58408-326, Brazil.

出版信息

Appl Microbiol Biotechnol. 2024 Feb 27;108(1):241. doi: 10.1007/s00253-024-13057-x.

Abstract

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.

摘要

本研究旨在开发、表征和评估两种含有 500µg/mL 姜黄素的纳米乳(NE)的抗菌和抗生物膜活性,姜黄素来自姜黄(Curcuma longa)。这些通过加热产生的 NE 含有橄榄油(5%)和表面活性剂吐温 80(5%)和司盘 80(2.5%),水为 100mL,并在 120 天内稳定。NE-2-CUR 的 Ø 为 165.40±2.56nm,PDI 为 0.254,ζ为-33.20±1.35mV,pH 值为 6.49,包封药物效率(EE)为 99%。NE-4-CUR 的 Ø 为 105.70±4.13nm,PDI 为 0.459,ζ为-32.10±1.45mV,pH 值为 6.40,EE 为 99.29%。通过 DRX 和 FTIR 进行结构表征,通过 DSC 和 TG 进行热特性表征,通过 SEM 进行形态学表征,表明 CUR 存在于 NE 中且没有明显变化,保持稳定。通过肉汤微量稀释法测定了 9 种革兰氏阳性和革兰氏阴性细菌以及对抗生素和生物膜有抗药性且产外排泵的肺炎克雷伯菌临床分离株的 MIC。NE 主要表现为抑菌作用。MIC 范围为 125-250µg/mL。最敏感的细菌是金黄色葡萄球菌和粪肠球菌,对于这两种细菌,NE-2-CUR 的 MIC 为 125µg/mL。还使用棋盘法评估了 NE-2-CUR 和 NE-4-CUR 与耐抗生素肺炎克雷伯菌临床分离株的相互作用。NE-2-CUR 和 NE-4-CUR 显示协同或相加作用;头孢他啶(CAZ)MIC 降低了 256 倍(K26-A2)至 2 倍(K29-A2)。此外,NE 抑制了这些分离株生物膜的形成。NE 的 MBIC 范围为 15.625-250µg/mL。因此,NE 表现出适合未来临床试验的理化特性,增强了 CAZ 的抗菌和抗生物膜活性,因此成为治疗多药耐药肺炎克雷伯菌引起的细菌感染的有前途的策略。要点:• NE 表现出适合未来临床试验的理化特性。• 当与头孢他啶联合使用时,NE 表现出协同/相加作用。• NE 抑制临床分离株生物膜的形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7167/10899360/55c1330cbcfd/253_2024_13057_Fig1_HTML.jpg

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