Anjum Anam, Chung Pooi-Yin, Ng Shiow-Fern
Centre for Drug Delivery Research, Faculty of Pharmacy, University Kebangsaan Malaysia 50300 Kuala Lumpur Malaysia
Department of Microbiology, International Medical University 57000 Kuala Lumpur Malaysia.
RSC Adv. 2019 May 7;9(25):14198-14208. doi: 10.1039/c9ra00125e.
Biofilms are gelatinous masses of microorganisms attached to wound surfaces. Previous studies suggest that biofilms generate resistance towards antibiotic treatments. It was reported that hydrogels containing xylitol and antibiotic combinations produced additive antibiofilm inhibition. However, hydrogel formulations lack specificity, due to which xylitol cannot penetrate into the biofilm matrix and gets easily degraded by bacterial beta lactamase enzymes. It was hypothesized that the incorporation of xylitol in PLGA (polylactic--glycolic acid) nanoparticles will enhance penetration into the EPS (extra polymeric substance) component of the biofilm matrix and potentially overcome the antibiotic resistance associated with the biofilms. The purpose of this study was to develop PLGA nanoparticles loaded with xylitol, which will enhance bacterial biofilm penetration. The nanoparticles were loaded with different amounts of xylitol (0.5-5% w/w) and characterized for physiochemical and drug release properties. The metabolic antibiofilm activity of the PLGA nanoparticles containing xylitol was demonstrated by an XTT assay using as references the cultures of () and () and the polymicrobial biofilms of both bacterial strains. Live/dead viability staining was also performed to investigate the viability ratio of bacterial cells present in the biofilms. The biofilm penetration study of the PLGA nanoparticles was assessed by combining the nanoparticles with conjugated concanavalin A (Con A)-fluorescein isothiocyanate (FITC) and by viewing using confocal laser scanning electron microscopy (CLSM). In conclusion, the PLGA nanoparticles loaded with xylitol were successfully developed and were found to promote the antibiofilm activity of xylitol in infected wounds.
生物膜是附着在伤口表面的微生物凝胶状聚集体。先前的研究表明,生物膜会产生对抗生素治疗的抗性。据报道,含有木糖醇和抗生素组合的水凝胶产生了相加性的抗生物膜抑制作用。然而,水凝胶制剂缺乏特异性,由于这个原因,木糖醇无法渗透到生物膜基质中,并且很容易被细菌β-内酰胺酶降解。据推测,将木糖醇掺入聚乳酸-乙醇酸共聚物(PLGA)纳米颗粒中将增强其对生物膜基质中胞外聚合物(EPS)成分的渗透,并有可能克服与生物膜相关的抗生素抗性。本研究的目的是开发负载木糖醇的PLGA纳米颗粒,以增强其对细菌生物膜的渗透。纳米颗粒负载了不同量的木糖醇(0.5 - 5% w/w),并对其理化性质和药物释放特性进行了表征。以()和()的培养物以及两种细菌菌株的混合微生物生物膜为对照,通过XTT测定法证明了含木糖醇的PLGA纳米颗粒的代谢性抗生物膜活性。还进行了活/死细胞活力染色,以研究生物膜中存在的细菌细胞的活力比率。通过将纳米颗粒与共轭伴刀豆球蛋白A(Con A)-异硫氰酸荧光素(FITC)结合,并使用共聚焦激光扫描电子显微镜(CLSM)观察,评估了PLGA纳米颗粒的生物膜渗透研究。总之,成功开发了负载木糖醇的PLGA纳米颗粒,并发现其能促进木糖醇在感染伤口中的抗生物膜活性。