Ahsan Anam, Barnes Timothy J, Thomas Nicky, Subramaniam Santhni, Prestidge Clive A
Centre for Pharmaceutical Innovation, UniSA Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
Drug Deliv Transl Res. 2025 Jun 12. doi: 10.1007/s13346-025-01890-0.
Conventional antibiotic therapies often fail to eradicate bacterial biofilms due to limited penetration, altered microenvironments, and the presence of persister cells, contributing to persistent and recurrent infections. As a result,the growing threat of antibiotic-resistant bacteria, particularly those forming biofilms, underscores the urgent need for alternative therapeutic strategies. Lipid-based drug delivery systems have emerged as effective nanocarriers for antimicrobials, offering a promising strategy to combat bacterial biofilms due to their biomimetic properties, biocompatibility, and ability to navigate the complex physical, chemical, and biological barriers posed by biofilms. In this study, we compared liquid crystal nanoparticles (LCNPs) and liposomes as delivery systems for gentamicin (GEN) against Escherichia coli (E. coli) (ATCC 25922 and ATCC 35218) in both planktonic and biofilm forms. Transmission electron microscopy analysis confirmed the particle size of GEN-loaded LCNPs (~ 200 nm) and GEN-loaded liposomes (~ 160 nm), with cubic-shaped LCNPs and lipid bilayer-structured liposomes which remained stable over three weeks at 4ºC. Loading GEN into lipid-based nanoparticles resulted in a two-fold reduction in minimum inhibitory concentration values, without significantly altering the minimum bactericidal concentration. Notably, GEN-LCNPs led to a significant fourfold (for E. coli ATCC 25922) and threefold (for E. coli ATCC 35218) reduction in inhibitory concentrations in biofilm states compared to unformulated GEN, achieving a minimum biofilm inhibitory concentration (MBIC) of 50 μg/mL and 100 μg/mL (P < 0.0001), respectively. In contrast, liposomes showed only a twofold reduction in MBIC values (100-150 μg/mL) for both bacterial biofilms. GEN-loaded LCNPs also reduced the E. coli ATCC 25922 colony-forming unit count by 5000-fold and 4000-fold, while liposomes with similar particle size did not significantly improve GEN's antimicrobial activity. Moreover, LCNPs improved GEN efficacy regardless of particle size or Pluronic concentration. In conclusion, our findings suggest that GEN-loaded LCNPs demonstrated superior antimicrobial efficacy against E. coli biofilms compared to liposomes, highlighting their potential as effective nanocarriers for combating antibiotic-resistant infections.
传统抗生素疗法往往无法根除细菌生物膜，原因在于其穿透性有限、微环境改变以及存在持留菌，这导致了持续性和复发性感染。因此，抗生素耐药菌，尤其是那些形成生物膜的细菌所带来的日益增长的威胁，凸显了对替代治疗策略的迫切需求。基于脂质的药物递送系统已成为有效的抗菌纳米载体，由于其仿生特性、生物相容性以及能够跨越生物膜所构成的复杂物理、化学和生物屏障的能力，为对抗细菌生物膜提供了一种有前景的策略。在本研究中，我们比较了液晶纳米颗粒（LCNPs）和脂质体作为庆大霉素（GEN）针对浮游态和生物膜态大肠杆菌（E. coli）（ATCC 25922和ATCC 35218）的递送系统。透射电子显微镜分析证实了负载GEN的LCNPs（约200纳米）和负载GEN的脂质体（约160纳米）的粒径，LCNPs为立方体形，脂质体为脂质双层结构，在4℃下三周内保持稳定。将GEN负载到基于脂质的纳米颗粒中导致最低抑菌浓度值降低了两倍，而最低杀菌浓度没有显著改变。值得注意的是，与未配制的GEN相比，GEN-LCNPs使生物膜状态下的抑菌浓度显著降低了四倍（对于大肠杆菌ATCC 25922）和三倍（对于大肠杆菌ATCC 35218），分别达到了50μg/mL和100μg/mL的最低生物膜抑菌浓度（MBIC）（P < 0.0001）。相比之下，脂质体对两种细菌生物膜的MBIC值仅降低了两倍（100 - 150μg/mL）。负载GEN的LCNPs还使大肠杆菌ATCC 25922的菌落形成单位数量减少了5000倍和4000倍，而具有相似粒径的脂质体并未显著提高GEN的抗菌活性。此外，无论粒径或普朗尼克浓度如何，LCNPs都提高了GEN的疗效。总之，我们的研究结果表明，与脂质体相比，负载GEN的LCNPs对大肠杆菌生物膜表现出卓越的抗菌效果，突出了它们作为对抗抗生素耐药感染的有效纳米载体的潜力。
