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聚(Eudragit)纳米载药胶束二元医用纳米流体的构建及其妥布霉素和白藜芦醇的载运:抗菌、溶血毒性和蛋白冠研究。

Binary Medical Nanofluids by Combination of Polymeric Eudragit Nanoparticles for Vehiculization of Tobramycin and Resveratrol: Antimicrobial, Hemotoxicity and Protein Corona Studies.

机构信息

Laboratorio de Nanobiomateriales, Centro de Investigación y Desarrollo en Fermentaciones Industriales (CINDEFI), Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP) -CONICET (CCT La Plata), Calle 47 y 115, (B1900AJI), La Plata, Buenos Aires, Argentina.

Instituto de Genética Veterinaria (IGEVET, UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, La Plata, Argentina.

出版信息

J Pharm Sci. 2021 Apr;110(4):1739-1748. doi: 10.1016/j.xphs.2021.01.005. Epub 2021 Jan 9.

Abstract

The development of smart nanoparticles (NPs) became a trend to enhance the delivery of drugs. In the present work, Tobramycin (TB), an aminoglycoside antibiotic that displays several undesirable side effects, has been encapsulated into cationic Eudragit®E100 (E100) NPs for the treatment of infections caused by Pseudomonas aeruginosa. Combination with neutral Eudragit®NE30D (NE30D) NPs containing resveratrol (RSV), a strong natural antioxidant, increased the antimicrobial activity of TB (75% higher than free TB). NPs were stabilized with 1.0% (w/v) poloxamer 188 (P188) or poloxamer 407 (P407) as surfactants. E100 NPs showed 83.3 ± 8.5%, and 70.1 ± 2.7 encapsulation efficiency (EE) of TB with P188 and P407 coatings, respectively. The presence of NPs was confirmed by DLS and TEM studies. TB was controlled released from NPs for 6 h. Hemotoxicity tests of NPs in the range of MIC values on human blood gave negative results. Analysis of Surface Plasmon Resonance verified that NE30D/P407/RSV does not interact with plasma proteins BSA, IgG or fibrinogen, besides E100/P188/TB interact with BSA, findings that are compatible with a negligible in vivo clearance of the nanovehicles. The obtained results show a potential binary fluid composed of two NPs to highly improve the effectiveness of conventional antibiotics.

摘要

智能纳米颗粒 (NPs) 的发展成为增强药物输送的一种趋势。在本工作中,妥布霉素 (TB) 是一种氨基糖苷类抗生素,具有多种不良副作用,已被包封到阳离子型 Eudragit®E100 (E100) NPs 中,用于治疗铜绿假单胞菌引起的感染。与含有白藜芦醇 (RSV) 的中性 Eudragit®NE30D (NE30D) NPs 结合使用,RSV 是一种强天然抗氧化剂,可提高 TB 的抗菌活性 (比游离 TB 高 75%)。 NPs 用 1.0%(w/v) 泊洛沙姆 188 (P188) 或泊洛沙姆 407 (P407) 作为表面活性剂稳定。E100 NPs 分别用 P188 和 P407 涂层显示出 83.3±8.5%和 70.1±2.7%的 TB 包封效率 (EE)。通过 DLS 和 TEM 研究证实了 NPs 的存在。TB 从 NPs 中控制释放 6 小时。在 MIC 值范围内对人血进行 NPs 的血液毒性测试得到了阴性结果。表面等离子体共振分析证实,NE30D/P407/RSV 与 BSA、IgG 或纤维蛋白原等血浆蛋白不相互作用,而 E100/P188/TB 与 BSA 相互作用,这些发现与纳米载体在体内清除率可忽略不计相符。所得结果表明,由两种 NPs 组成的二元流体具有提高传统抗生素有效性的潜力。

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