用于消除耐甲氧西林金黄色葡萄球菌生物膜的电荷自适应植物化学纳米颗粒

IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Asian Journal of Pharmaceutical Sciences Pub Date : 2024-06-01 DOI:10.1016/j.ajps.2024.100923
Xilong Cui , Fanhui Liu , Shuang Cai , Tingting Wang , Sidi Zheng , Xinshu Zou , Linlin Wang , Siqi He , Yanhua Li , Zhiyun Zhang
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引用次数: 0

摘要

MRSA 的内在耐药性和生物膜对抗生素的耐受性给 MRSA 生物膜感染的抗生素治疗带来了挑战。基于植物化学物质的纳米平台是治疗生物膜感染的一种前景广阔的新兴方法。然而,由于药物负载能力低且缺乏选择性,其疗效受到限制。在此,我们构建了一种表面电荷自适应的植物化学纳米粒子,该粒子具有较高的isisiquiritigenin(ISL)载药量,可有效治疗MRSA生物膜。该研究合成了一种带有脂肪酶响应酯键的二聚 ISL 原药(ISL-G2),然后将其包封在两亲性季铵化低聚壳聚糖中。获得的 ISL-G2 负载 NPs 表面带正电荷,可通过静电作用与顺式-乌头基-d-酪氨酸(CA-Tyr)结合,从而获得 ISL-G2@TMDCOS-Tyr NPs。这些 NPs 保持了带负电荷的表面,从而延长了血液循环时间。由于生物膜中的 pH 值较低,CA-Tyr 的快速脱落导致其表面电荷由负变正,从而增强了 NPs 在生物膜中的积累和渗透。随后,pH 触发释放的 d- 酪氨酸分散了生物膜,而脂肪酶触发释放的 ISL 则有效地杀死了生物膜上的 MRSA。在 MRSA 生物膜感染伤口模型上进行了体内研究。与未经处理的伤口相比,这种基于植物化学物质的系统可使生物膜 MRSA 减少 2 log CFU(99 %)(P <0.001),对小鼠的生物毒性可忽略不计。这种植物化学二聚体纳米平台显示出长期治疗耐药细菌感染的巨大潜力。
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Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms

The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.

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来源期刊
Asian Journal of Pharmaceutical Sciences
Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
18.30
自引率
2.90%
发文量
11
审稿时长
14 days
期刊介绍: The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.
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