Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, Espoo, Finland,
Department of Chemistry and Materials Science, School of Chemical Engineering, Aalto University, Espoo, Finland,
Int J Nanomedicine. 2018 Nov 28;13:7939-7957. doi: 10.2147/IJN.S182611. eCollection 2018.
Antibiotic resistance is a growing concern in health care. Methicillin-resistant (MRSA), forming biofilms, is a common cause of resistant orthopedic implant infections. Gentamicin is a crucial antibiotic preventing orthopedic infections. Silica-gentamicin (SiO-G) delivery systems have attracted significant interest in preventing the formation of biofilms. However, compelling scientific evidence addressing their efficacy against planktonic MRSA and MRSA biofilms is still lacking, and their safety has not extensively been studied.
In this work, we have investigated the effects of SiO-G nanohybrids against planktonic MRSA as well as MRSA and biofilms and then evaluated their toxicity in zebrafish embryos, which are an excellent model for assessing the toxicity of nanotherapeutics.
SiO-G nanohybrids inhibited the growth and killed planktonic MRSA at a minimum concentration of 500 µg/mL. SiO-G nanohybrids entirely eradicated cells in biofilms at a minimum concentration of 250 µg/mL and utterly deformed their ultrastructure through the deterioration of bacterial shapes and wrinkling of their cell walls. Zebrafish embryos exposed to SiO-G nanohybrids (500 and 1,000 µg/mL) showed a nonsignificant increase in mortality rates, 13.4±9.4 and 15%±7.1%, respectively, mainly detected 24 hours post fertilization (hpf). Frequencies of malformations were significantly different from the control group only 24 hpf at the higher exposure concentration.
Collectively, this work provides the first comprehensive in vivo assessment of SiO-G nanohybrids as a biocompatible drug delivery system and describes the efficacy of SiO-G nanohybrids in combating planktonic MRSA cells and eradicating biofilms.
抗生素耐药性是医疗保健领域日益关注的问题。耐甲氧西林金黄色葡萄球菌(MRSA)形成生物膜,是导致骨科植入物感染的常见原因。庆大霉素是预防骨科感染的关键抗生素。硅-庆大霉素(SiO-G)递送系统在预防生物膜形成方面引起了极大的兴趣。然而,针对浮游 MRSA 和 MRSA 生物膜的疗效,仍缺乏强有力的科学证据,其安全性也尚未广泛研究。
在这项工作中,我们研究了 SiO-G 纳米杂化物对浮游 MRSA 以及 MRSA 生物膜的作用,然后在斑马鱼胚胎中评估了它们的毒性,斑马鱼胚胎是评估纳米治疗剂毒性的优秀模型。
SiO-G 纳米杂化物在最低浓度 500 µg/mL 时抑制浮游 MRSA 的生长并杀死浮游 MRSA。SiO-G 纳米杂化物在最低浓度 250 µg/mL 时完全根除生物膜中的细胞,并通过破坏细菌形状和使细胞壁起皱来完全改变其超微结构。暴露于 SiO-G 纳米杂化物(500 和 1000 µg/mL)的斑马鱼胚胎的死亡率分别无显著增加,为 24 小时后受精(hpf)时的 13.4±9.4%和 15%±7.1%。仅在较高暴露浓度时,24 hpf 时畸形频率与对照组有显著差异。
总的来说,这项工作首次全面评估了 SiO-G 纳米杂化物作为生物相容药物递送系统的体内情况,并描述了 SiO-G 纳米杂化物在对抗浮游 MRSA 细胞和根除生物膜方面的功效。