Department of Otorhinolaryngology and Head and Neck Surgery, Medical University of Vienna, Vienna, Austria.
Biocatalysis and Biosensing Laboratory, Department of Food Sciences and Technology, BOKU-University of Natural Resources and Life Sciences, Vienna, Austria.
Carbohydr Polym. 2018 Nov 15;200:35-42. doi: 10.1016/j.carbpol.2018.07.072. Epub 2018 Jul 25.
Bacterial biofilms play a key role during infections, which are associated with an increased morbidity and mortality. The classical antibiotic therapy cannot eradicate biofilm-related infections because biofilm bacteria display high drug resistance due to biofilm matrix. Thus, novel drug delivery to overcome biofilm resistance and eliminate biofilm-protected bacteria is needed to be developed. In this study, positively charged chitosan nanoparticles (CSNP) loaded with oxacillin (Oxa) and Deoxyribonuclease I (CSNP-DNase-Oxa) were fabricated. The antibiofilm activity was evaluated against Staphylococcus aureus biofilms. Biofilm architecture on silicone surfaces was investigated by scanning electron microscopy (SEM). Confocal laser scanning microscopy (CLSM) was used to examine live/dead organisms within biofilm. CSNP-DNase-Oxa exhibited higher antibiofilm activity than Oxa-loaded nanoparticles without DNase (CSNP-Oxa) and free Oxa (Oxa and Oxa + DNase) at each concentration in all in-vitro tests. CSNP-DNase-Oxa inhibited biofilm formation in-vitro and eradicated mature biofilm effectively. CSNP-DNase-Oxa could disrupt the biofilm formation through degradation of eDNA, reduced biofilm thickness and the amount of viable cells on silicone. Repeated treatment with CSNP-DNase-Oxa for two days resulted in 98.4% biofilm reduction. Moreover, CSNP-DNase-Oxa was not only able to affect the biofilm of a standard S. aureus strain, but also showed the highest eradication of biofilms of clinical isolates compared with control groups. These results suggest the potential applicability of NPs for the treatment of biofilm-related infections and provide a platform for designing novel drug delivery with more functions.
细菌生物膜在感染过程中起着关键作用，与发病率和死亡率的增加有关。经典的抗生素治疗不能根除生物膜相关感染，因为生物膜细菌由于生物膜基质而表现出高耐药性。因此，需要开发新的药物输送方法来克服生物膜耐药性并消除生物膜保护的细菌。在这项研究中，制备了载有苯唑西林（Oxa）和脱氧核糖核酸酶 I（CSNP-DNase-Oxa）的带正电荷的壳聚糖纳米颗粒（CSNP）。评估了其针对金黄色葡萄球菌生物膜的抗生物膜活性。通过扫描电子显微镜（SEM）研究了硅酮表面上的生物膜结构。共聚焦激光扫描显微镜（CLSM）用于检查生物膜内的活/死生物。在所有体外试验中，与不含 DNase 的载有 Oxa 的纳米颗粒（CSNP-Oxa）和游离 Oxa（Oxa 和 Oxa+DNase）相比，CSNP-DNase-Oxa 在每个浓度下均表现出更高的抗生物膜活性。CSNP-DNase-Oxa 可在体外抑制生物膜形成并有效根除成熟生物膜。CSNP-DNase-Oxa 可以通过降解 eDNA、减少生物膜厚度和硅酮上存活细胞的数量来破坏生物膜形成。用 CSNP-DNase-Oxa 重复治疗两天可使生物膜减少 98.4%。此外，CSNP-DNase-Oxa 不仅能够影响标准金黄色葡萄球菌菌株的生物膜，而且与对照组相比，对临床分离株的生物膜的清除率最高。这些结果表明 NPs 具有治疗生物膜相关感染的潜在应用前景，并为设计具有更多功能的新型药物输送提供了平台。
