Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic; Faculty of Mechanical Engineering, Czech Technical University in Prague, Prague 6, Czech Republic; Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic.
Department of Composites and Carbon Materials, Institute of Rock Structure and Mechanics, Academy of Sciences of the Czech Republic, Prague 8, Czech Republic; Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic.
Eur J Pharm Biopharm. 2019 Jul;140:50-59. doi: 10.1016/j.ejpb.2019.04.021. Epub 2019 May 2.
The aim of this study was to develop a biodegradable nanostructured electrospun layer based on collagen (COL), hydroxyapatite nanoparticles (HA), vancomycin hydrochloride (V), gentamicin sulphate (G) and their combination (VG) for the treatment of prosthetic joint infections and the prevention of infection during the joint replacement procedure. COL/HA layers containing different amounts of HA (0, 5 and 15 wt%) were tested for the in vitro release kinetics of antibiotics, antimicrobial activity against MRSA, gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis isolates and cytocompatibility using SAOS-2 bone-like cells. The results revealed that the COL/HA layers released high concentrations of vancomycin and gentamicin for 21 days and performed effectively against the tested clinically-relevant bacterial isolates. The presence of HA in the collagen layers was found not to affect the release kinetics of the vancomycin from the layers loaded only with vancomycin or its combination with gentamicin. Conversely, the presence of HA slowed down the release of gentamicin from the COL/HA layers loaded with gentamicin and its combination with vancomycin. The combination of both antibiotics exerted a positive effect on the prolongation of the conversion of vancomycin into its degradation products. All the layers tested with different antibiotics exhibited potential antibacterial activity with respect to both the tested staphylococci isolates and enterococci. The complemental effect of vancomycin was determined against both gentamicin-resistant Staphylococcus epidermidis and Enterococcus faecalis in contrast to the application of gentamicin as a single agent. This combination was also found to be more effective against MRSA than is vancomycin as a single agent. Importantly, this combination of vancomycin and gentamicin in the COL/HA layers exhibited sufficient cytocompatibility to SAOS-2, which was independent of the HA content. Conversely, only gentamicin caused the death of SAOS-2 independently of HA content and only vancomycin stimulated SAOS-2 behaviour with an increased concentration of HA in the COL/HA layers. In conclusion, COL/HA layers with 15 wt% of HA impregnated with vancomycin or with a combination of vancomycin and gentamicin offer a promising treatment approach and the potential to prevent infection during the joint replacement procedures.
本研究旨在开发一种基于胶原（COL）、羟基磷灰石纳米粒子（HA）、盐酸万古霉素（V）、硫酸庆大霉素（G）及其组合（VG）的可生物降解的纳米结构电纺层，用于治疗人工关节感染和预防关节置换过程中的感染。测试了含有不同 HA 含量（0、5 和 15wt%）的 COL/HA 层中抗生素的体外释放动力学、对 MRSA、耐庆大霉素表皮葡萄球菌和粪肠球菌分离株的抗菌活性以及使用 SAOS-2 骨样细胞的细胞相容性。结果表明，COL/HA 层在 21 天内释放出高浓度的万古霉素和庆大霉素，对测试的临床相关细菌分离株有效。在仅加载万古霉素或万古霉素与庆大霉素组合的 COL/HA 层中，HA 的存在不影响万古霉素的释放动力学。相反，HA 的存在减缓了 COL/HA 层中加载的庆大霉素及其与万古霉素组合的释放。两种抗生素的组合对延长万古霉素转化为降解产物具有积极影响。所有测试的含有不同抗生素的层对测试的葡萄球菌分离株和肠球菌均表现出潜在的抗菌活性。与单独使用庆大霉素相比，万古霉素对耐庆大霉素表皮葡萄球菌和粪肠球菌均表现出互补作用。与单独使用万古霉素相比，该组合对 MRSA 也更有效。重要的是，COL/HA 层中万古霉素和庆大霉素的组合对 SAOS-2 具有足够的细胞相容性，且与 HA 含量无关。相反，仅庆大霉素会导致 SAOS-2 死亡，而与 HA 含量无关，仅万古霉素会刺激 SAOS-2 行为，COL/HA 层中的 HA 浓度增加。总之，含有 15wt%HA 的 COL/HA 层浸渍万古霉素或万古霉素和庆大霉素的组合为关节置换过程中提供了一种有前景的治疗方法和预防感染的潜力。
