Anacardic acid encapsulated solid lipid nanoparticles forStaphylococcus aureusbiofilm therapy: chitosan and DNase coating improves antimicrobial activity
Anacardic acid encapsulated solid lipid nanoparticles forStaphylococcus aureusbiofilm therapy: chitosan and DNase coating improves antimicrobial activity
复制标题
DOI：
10.1007/s13346-020-00795-4
复制
发表时间：
2020-06-09
影响因子：
5.4
通讯作者：
Singh, Sanjay
中科院分区：
文献类型：
--
作者：
Anjum, Md Meraj;Patel, Krishna Kumar;Singh, Sanjay
由于抗菌素耐药性的演变，生物膜介导的细菌感染是传染病进展的关键因素。由于生物膜引发的耐药性增加，涉及抗生素的传统疗法不足以治疗此类感染。为了克服这一挑战，我们开发了负载漆树酸 (Ana) 的固体脂质纳米颗粒 (SLN)，并进一步涂有壳聚糖和 DNase (Ana-SLNs-CH-DNase)。假设 DNase 涂层可降解 e-DNA，而涂层壳聚糖可产生带正电荷的 SLN，对生物膜具有额外的粘附力。使用均质化方法开发 SLN，并进一步评估粒径、多分散指数、zeta 电位和包封效率。通过 FT-IR 研究证实了药物赋形剂的相容性，同时通过 X 射线衍射研究证实了 SLN 中 Ana 的封装。 SLN 具有长达 24 小时的缓释能力和在室温下长达 3 个月的优异稳定性。研究发现，所开发的 SLN 对人永生化角质形成细胞 (HaCaT) 细胞无毒，同时对金黄色葡萄球菌具有显着更高的抗菌功效。所开发的SLN对最小生物膜抑制浓度和最小生物膜根除浓度的优异效果进一步证实了所开发的制剂策略的优越性。通过共焦激光扫描显微镜证实，与对照相比，在发达的 SLN 中观察到生物膜厚度和生物量显着（p < 0.05）减少。总的来说，结果表明所开发的制剂策略在克服生物膜介导的抗菌素耐药性方面具有增强的功效。
Biofilm mediated bacterial infections are the key factors in the progression of infectious diseases due to the evolution of antimicrobial resistance. Traditional therapy involving antibiotics is not adequate enough for treatment of such infections due to the increased resistance triggered by biofilm. To overcome this challenge, we developed anacardic acid (Ana) loaded solid lipid nanoparticles (SLNs), further coated with chitosan and DNase (Ana-SLNs-CH-DNase). The DNase coating was hypothesized to degrade the e-DNA, while chitosan was coated to yield positively charged SLNs with additional adhesion to biofilms. The SLNs were developed using homogenization method and further evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Drug excipient compatibility was confirmed by using FT-IR study, while encapsulation of Ana in SLNs was confirmed by X-ray diffraction study. The SLNs demonstrated sustained release for up to 24 h and excellent stability at room temperature for up to 3 months. The developed SLNs were found non-toxic against human immortalized keratinocyte (HaCaT) cells while demonstrated remarkably higher antimicrobial efficacy againstStaphylococcus aureus. Excellent effect of the developed SLNs on minimum biofilm inhibition concentration and minimum biofilm eradication concentration further confirmed the superiority of the developed formulation strategy. A significant (p< 0.05) reduction in biofilm thickness and biomass, as confirmed by confocal laser scanning microscopy, was observed in the case of developed SLNs in comparison with control. Cumulatively, the results suggest the enhanced efficacy of the developed formulation strategy to overcome the biofilm-mediated antimicrobial resistance.