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