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聚(甲基丙烯酸缩水甘油酯)大分子组装体作为抗菌溶菌酶的生物相容性纳米载体。

Poly(glycidyl methacrylate) macromolecular assemblies as biocompatible nanocarrier for the antimicrobial lysozyme.

机构信息

Department of Organic and Inorganic Chemistry, Institute of Chemical Research "Andrés M. del Río" (IQAR), Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain.

Department of Chemical Engineering, Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain.

出版信息

Int J Pharm. 2021 Jun 15;603:120695. doi: 10.1016/j.ijpharm.2021.120695. Epub 2021 May 11.

Abstract

The antimicrobial lysozyme (Lys) was electrostatically incorporated to negatively charged crosslinked poly(glycidyl methacrylate) (c-PGMA) macromolecular assemblies. The resulting material was characterized by AFM, infrared spectra, water contact angle measurements and the staining with the primary amino specific dye fluorescamine. c-PGMA nanoparticles were successfully loaded with Lys reaching ratios of 27.3 ± 4.0 and 22.5 ± 1.7 mg Lys/g polymer for c-PGMA suspensions and functionalized glass substrates, respectively. Lys-loaded c-PGMA caused clear inhibition zones on S. aureus and E. coli in comparison to neat c-PGMA. c-PGMA functionalized surfaces were intrinsically resistant to colonization, but the incorporation of Lys added resistance to bacterial attachment and allowed keeping surfaces clean of bacterial cells for both strains. A relatively rapid release (24 h) of Lys was observed at physiological pH (7.4). In addition, c-PGMA functionalized substrates could be reloaded several times without losing capacity. c-PGMA macromolecular assemblies did not display cytotoxicity to human dermal fibroblasts as shown in 24 h MTT assays. This work demonstrated that c-PGMA assemblies display durable antibacterial activity, biocompatibility, and full reloading capacity with antimicrobial peptides. c-PGMA functionalized materials have potential application as nanocarriers for anti-infective uses.

摘要

抗菌溶菌酶(Lys)通过静电作用被整合到带负电荷的交联聚(甲基丙烯酸缩水甘油酯)(c-PGMA)大分子组装体中。通过原子力显微镜、红外光谱、水接触角测量和与碱性染料荧光胺的染色对所得材料进行了表征。c-PGMA 纳米粒子成功负载 Lys,达到了 27.3±4.0 和 22.5±1.7 mg Lys/g 聚合物的比率,分别对应于 c-PGMA 悬浮液和功能化玻璃基底。与纯 c-PGMA 相比,负载 Lys 的 c-PGMA 对金黄色葡萄球菌和大肠杆菌引起了明显的抑制区。c-PGMA 功能化表面本身对定植具有抗性,但掺入 Lys 增加了对细菌附着的抗性,并允许两种菌株的表面保持无细菌细胞。在生理 pH(7.4)下观察到 Lys 的相对快速释放(24 小时)。此外,c-PGMA 功能化基底可以多次重新加载而不会失去容量。如 24 小时 MTT 测定所示,c-PGMA 大分子组装体对人皮肤成纤维细胞没有细胞毒性。这项工作表明,c-PGMA 组装体具有持久的抗菌活性、生物相容性和完全的再负载能力,可用于抗菌肽。c-PGMA 功能化材料具有作为抗感染用途的纳米载体的潜在应用。

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