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封装于聚乳酸-乙醇酸共聚物(PLGA)纳米颗粒中的G17和G19肽对O157:H7和耐甲氧西林金黄色葡萄球菌(MRSA)具有强效且特异的抗菌活性。

Potent and Specific Antibacterial Activity against O157:H7 and Methicillin Resistant (MRSA) of G17 and G19 Peptides Encapsulated into Poly-Lactic-Co-Glycolic Acid (PLGA) Nanoparticles.

作者信息

Gómez-Sequeda Nicolás, Ruiz Jennifer, Ortiz Claudia, Urquiza Mauricio, Torres Rodrigo

机构信息

Grupo de Investigación en Bioquímica y Microbiología (GIBIM), Universidad Industrial de Santander, Bucaramanga 680002, Colombia.

Escuela de Microbiología, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga 680002, Colombia.

出版信息

Antibiotics (Basel). 2020 Jul 7;9(7):384. doi: 10.3390/antibiotics9070384.

Abstract

Antimicrobial peptides constitute an excellent alternative against conventional antibiotics because of their potent antimicrobial spectrum, unspecific action mechanism and low capacity to produce antibiotic resistance. However, a potential use of these biological molecules as therapeutic agents is threatened by their low stability and susceptibility to proteases. In order to overcome these limitations, encapsulation in biocompatible polymers as poly-lactic-glycolic-acid (PLGA) is a promising alternative for increasing their stability and bioavailability. In this work, the effect of new synthetic antimicrobial peptides GIBIM-P5S9K (G17) and GAM019 (G19) encapsulated on PLGA and acting against methicillin resistant (MRSA) and O157:H7 was studied. PLGA encapsulation allowed us to load around 7 µg AMPs/mg PLGA with an efficiency of 90.5%, capsule sizes around 290 nm and positive charges. Encapsulation improved antimicrobial activity, decreasing MIC50 from 1.5 to 0.2 (G17NP) and 0.7 (G19NP) µM against MRSA, and from 12.5 to 3.13 µM for O157:H7. Peptide loaded nanoparticles could be a bacteriostatic drug with potential application to treat these bacterial O157:H7 and MRSA infections, with a slow and gradual release.

摘要

抗菌肽因其强大的抗菌谱、非特异性作用机制以及产生抗生素耐药性的能力较低,成为传统抗生素的极佳替代品。然而,这些生物分子作为治疗剂的潜在用途受到其低稳定性和对蛋白酶敏感性的威胁。为了克服这些限制,将其封装在生物相容性聚合物如聚乳酸 - 乙醇酸(PLGA)中是提高其稳定性和生物利用度的一种有前景的替代方法。在这项工作中,研究了封装在PLGA中的新型合成抗菌肽GIBIM - P5S9K(G17)和GAM019(G19)对耐甲氧西林金黄色葡萄球菌(MRSA)和O157:H7的作用。PLGA封装使我们能够以90.5%的效率在每毫克PLGA中负载约7μg抗菌肽,胶囊尺寸约为290nm且带正电荷。封装提高了抗菌活性,针对MRSA,MIC50从1.5降至0.2(G17NP)和0.7(G19NP)μM,针对O157:H7从12.5降至3.13μM。负载肽的纳米颗粒可能是一种具有抑菌作用的药物,有潜力用于治疗这些O157:H7和MRSA细菌感染,并具有缓慢且逐渐释放的特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a4c/7400247/21eb10113dbb/antibiotics-09-00384-g001.jpg

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