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万古霉素从双层聚左旋乳酸涂层植入物中的控释机制以预防细菌感染

Controlled Release Mechanism of Vancomycin from Double-Layer Poly-L-Lactic Acid-Coated Implants for Prevention of Bacterial Infection.

作者信息

Thamvasupong Papon, Viravaidya-Pasuwat Kwanchanok

机构信息

Department of Chemical Engineering, Faculty of Engineering, King Mongkut's University of Technology Thonburi, 126 Pracha-Utid Rd., Bangkok 10140, Thailand.

Biological Engineering Program, Faculty of Engineering, King Mongkut's University of Technology Thonburi, 126 Pracha-Utid Rd., Bangkok 10140, Thailand.

出版信息

Polymers (Basel). 2022 Aug 26;14(17):3493. doi: 10.3390/polym14173493.

Abstract

Implantation failure due to bacterial infection incurs significant medical expenditure annually, and treatment tends to be complicated. This study proposes a method to prevent bacterial infection in implants using an antibiotic delivery system consisting of vancomycin loaded into poly-L-lactic acid (PLLA) matrices. A thin layer of this antibiotic-containing polymer was formed on stainless steel surfaces using a simple dip-coating method. SEM images of the polymeric layer revealed a honeycomb structure of the PLLA network with the entrapment of vancomycin molecules inside. In the in vitro release study, a rapid burst release was observed, followed by a sustained release of vancomycin for approximately 3 days. To extend the release time, a drug-free topcoat of PLLA was introduced to provide a diffusion resistance layer. As expected, the formulation with the drug-free topcoat exhibited a significant extension of the release time to approximately three weeks. Furthermore, the bonding strength between the double-layer polymer and the stainless steel substrate, which was an important property reflecting the quality of the coating, significantly increased compared to that of the single layer to the level that met the requirement for medical coating applications. The release profile of vancomycin from the double-layer PLLA film was best fitted with the Korsmeyer-Peppas model, indicating a combination of Fickian diffusion-controlled release and a polymer relaxation mechanism. More importantly, the double-layer vancomycin-PLLA coating exhibited antibacterial activity against , as confirmed by the agar diffusion assay, the bacterial survival assay, and the inhibition of bacterial surface colonization without being toxic to normal cells (L929). Our results showed that the proposed antibiotic delivery system using the double-layer PLLA coating is a promising solution to prevent bacterial infection that may occur after orthopedic implantation.

摘要

由于细菌感染导致的植入失败每年都会产生巨额医疗费用,而且治疗往往很复杂。本研究提出了一种使用由负载万古霉素的聚-L-乳酸(PLLA)基质组成的抗生素递送系统来预防植入物细菌感染的方法。使用简单的浸涂法在不锈钢表面形成了一层含有这种抗生素的聚合物薄层。聚合物层的扫描电子显微镜图像显示PLLA网络呈蜂窝状结构,万古霉素分子被困在其中。在体外释放研究中,观察到了快速的突释,随后万古霉素持续释放约3天。为了延长释放时间,引入了不含药物的PLLA顶涂层以提供扩散阻力层。正如预期的那样,带有不含药物顶涂层的制剂的释放时间显著延长至约三周。此外,双层聚合物与不锈钢基材之间的结合强度(这是反映涂层质量的一项重要性能)与单层相比显著提高,达到了满足医疗涂层应用要求的水平。万古霉素从双层PLLA膜的释放曲线最符合Korsmeyer-Peppas模型,表明是菲克扩散控制释放和聚合物松弛机制的结合。更重要的是,双层万古霉素-PLLA涂层对[具体细菌名称未给出]表现出抗菌活性,这通过琼脂扩散试验、细菌存活试验以及对细菌表面定植的抑制得到证实,且对正常细胞(L929)无毒。我们的结果表明,所提出的使用双层PLLA涂层的抗生素递送系统是预防骨科植入后可能发生的细菌感染的一种有前景的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c93d/9460839/75308bb7cad1/polymers-14-03493-g001.jpg

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