LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto 4050-313, Portugal.
Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology KU Leuven, Leuven 3001, Belgium.
ACS Appl Mater Interfaces. 2021 Sep 15;13(36):42329-42343. doi: 10.1021/acsami.1c05124. Epub 2021 Aug 31.
Bacterial biofilms are a major health concern, mainly due to their contribution to increased bacterial resistance to well-known antibiotics. The conventional treatment of biofilms represents a challenge, and frequently, eradication is not achieved with long-lasting administration of antibiotics. In this context, the present work proposes an innovative therapeutic approach that is focused on the encapsulation of -acetyl-l-cysteine (NAC) into lipid nanoparticles (LNPs) functionalized with d-amino acids to target and disrupt bacterial biofilms. The optimized formulations presented a mean hydrodynamic diameter around 200 nm, a low polydispersity index, and a high loading capacity. These formulations were stable under storage conditions up to 6 months. biocompatibility studies showed a low cytotoxicity effect in fibroblasts and a low hemolytic activity in human red blood cells. Nevertheless, unloaded LNPs showed a higher hemolytic potential than NAC-loaded LNPs, which suggests a safer profile of the latter. The antibiofilm efficacy of the developed formulations was tested against (Gram-positive) and (Gram-negative) mature biofilms. The results showed that the NAC-loaded LNPs were ineffective against biofilms, while a significant reduction of biofilm biomass and bacterial viability in biofilms were observed. In a more complex therapeutic approach, the LNPs were further combined with moxifloxacin, revealing a beneficial effect between the LNPs and the antibiotic against biofilms. Both alone and in combination with moxifloxacin, unloaded and NAC-loaded LNPs functionalized with d-amino acids showed a great potential to reduce bacterial viability, with no significant differences in the presence or absence of NAC. However, the presence of NAC in NAC-loaded functionalized LNPs shows a safer profile than the unloaded LNPs, which is beneficial for an application. Overall, the developed formulations present a potential therapeutic approach against biofilms, alone or in combination with antibiotics.
细菌生物膜是一个主要的健康问题，主要是因为它们导致细菌对抗生素的耐药性增加。生物膜的传统治疗方法是一个挑战，经常使用抗生素进行长期治疗也无法完全清除生物膜。在这种情况下，本工作提出了一种创新的治疗方法，该方法侧重于将 -乙酰-l-半胱氨酸 (NAC) 封装到功能化有 D-氨基酸的脂质纳米颗粒 (LNPs) 中，以靶向和破坏细菌生物膜。优化的配方具有约 200nm 的平均水动力学直径、低多分散指数和高载药量。这些配方在储存条件下稳定，可稳定 6 个月。生物相容性研究表明，在成纤维细胞中表现出低细胞毒性作用，在人红细胞中表现出低溶血活性。然而，未负载的 LNPs 比负载 NAC 的 LNPs 具有更高的溶血潜力，这表明后者具有更安全的特性。开发的配方的抗生物膜功效针对 (革兰氏阳性) 和 (革兰氏阴性) 成熟生物膜进行了测试。结果表明，负载 NAC 的 LNPs 对 生物膜无效，而 生物膜的生物膜生物量和细菌活力显著降低。在更复杂的治疗方法中，LNPs 进一步与莫西沙星结合，显示出 LNPs 与抗生素对 生物膜的有益作用。未负载和负载 NAC 的 LNPs 单独使用或与莫西沙星联合使用时，均具有降低细菌活力的巨大潜力，而 NAC 的存在与否没有显著差异。然而，在负载 NAC 的功能化 LNPs 中存在 NAC 比未负载的 LNPs 具有更安全的特性，这有利于实际应用。总体而言，开发的配方具有针对 生物膜的潜在治疗方法，无论是单独使用还是与抗生素联合使用。
