Antibiotic entrapment in antibacterial micelles as a novel strategy for the delivery of challenging antibiotics from silica nanoparticles
Antibiotic entrapment in antibacterial micelles as a novel strategy for the delivery of challenging antibiotics from silica nanoparticles
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DOI：
10.1016/j.micromeso.2023.112841
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发表时间：
2023-10-10
影响因子：
5.2
通讯作者：
Pikramenou，Zoe
中科院分区：
文献类型：
--
作者：
Muguruza，Asier R.;Odyniec，Maria L.;Pikramenou，Zoe
二氧化硅材料由于其低毒性和生物相容性而在生物医学应用中作为复合材料和药物递送平台受到欢迎。介孔二氧化硅纳米颗粒是一种具有高比表面积的多孔二氧化硅骨架的药物载体。在制备介孔二氧化硅框架（最常见的是MCM-41）时，由于模板在环境和人类健康中的高毒性，有效去除负责引入多孔网络的模板十六烷基三甲基溴化铵（CTAB）是关键步骤。在这项工作中，我们提出了一种新的一锅法，在二氧化硅框架内引入具有挑战性的抗生素，而不需要有毒的模板，而是使用抗菌剂形成胶束。我们证明，胶束形成的十六烷基氯化吡啶（CPC），一种已知的抗菌剂，截留抗生素，如利福平和环丙沙星。广泛的NMR研究阐明了CPC胶束内抗生素的精确定位。环丙沙星被放置在外部和栅栏区域之间，而利福平被进一步定位到疏水CPC胶束核心中。在这两种情况下，二氧化硅框架的形成可以围绕CPC-抗生素负载的胶束构建。所得的二氧化硅纳米颗粒显示出CPC和抗生素试剂的负载、多孔性和在二氧化硅框架内的胶束破裂后的双重抗菌释放。该设计不仅提供了形成多孔框架的治疗设计策略，而且还突出了纳米颗粒系统中精确抗生素剂量和释放的潜力。
Silica materials are popular in biomedical applications as composites and drug delivery platforms due to their low toxicity and biocompatibility. Mesoporous silica nanoparticles are attractive drug delivery systems based on their porous silica framework with high surface area. In the preparation of mesoporous silica frameworks, most commonly, MCM-41, the efficient removal of the template responsible for introducing porous networks, cetyltrimethyl ammonium bromide (CTAB), is a critical step due to the template's high toxicity in the environment and human health. In this work, we present a new one-pot approach of introducing challenging antibiotics within a silica framework without the need of toxic templates, but instead using micelle formation by an antibacterial agent. We demonstrate that micelles formed by cetylpyridinium chloride (CPC), a known antibacterial agent, entrap antibiotics such as rifampicin and ciprofloxacin. Extensive NMR studies elucidate the precise localisation of the antibiotic within the CPC micelle. Ciprofloxacin is placed between the outer and palisade region while rifampicin is located further into the hydrophobic CPC micelle core. In both cases, the formation of the silica framework can be built around the CPC-antibiotic loaded micelles. The resulting silica nanoparticles show loading of both CPC and antibiotic agents, porosity and dual antibacterial release upon disruption of the micelle within the silica framework. The design not only provides a strategy of a therapeutic design to form porous frameworks but also highlights the potential of precise antibiotic dose and release in nanoparticle systems.