Amer Ahmed M, Charnock Colin, Nguyen Sanko
Department of Life Sciences and Health, Oslo Metropolitan University (OsloMet), Oslo, Norway.
Department of Life Sciences and Health, Oslo Metropolitan University (OsloMet), Oslo, Norway.
Int J Pharm. 2025 Jan 25;669:125088. doi: 10.1016/j.ijpharm.2024.125088. Epub 2024 Dec 18.
This study focused on the development of cholesterol-free fusogenic liposomes with different surface charge with the aim of improving biofilm penetration. In vitro assessments of the liposomes included physical stability, biocompatibility, fusion with microbial cells, and the ability to penetrate established biofilms. Using dynamic light scattering, cholesterol-free, fusogenic liposomes were found to be < 200 nm in size with small size distribution (PDI < 0.1) and physically stable for a year when stored at 4 °C. Transmission electron microscopy (TEM) images confirmed vesicular sizes for selected liposomal formulations. Liposomal ability to fuse with microbial cells was assessed using lipid mixing and flow cytometer assays. Fusion levels were found to be higher with Escherichia coli compared to Staphylococcus aureus and Candida albicans regardless of the liposomal charge. Neutral liposomes exhibited highest fusion, followed by cationic and anionic liposomes, respectively. Our investigations demonstrated that fusion is a multifactorial process influenced by the chemical composition of the liposomes, the liposomal surface charge, and components of the microbial cell envelope. Penetration and retention within preformed S. aureus biofilms were assessed for liposomes with various surface charges. All liposomes, regardless of surface charge, were capable of penetrating and diffusing through the biofilm matrix. However, cationic liposomes displayed greatest interaction and retention. Biocompatibility was confirmed through haemolysis and cytotoxicity studies. The cholesterol-free fusogenic liposomes developed in this study demonstrated promising potential as drug delivery systems for incorporating antimicrobial agents for biofilm treatment.
本研究聚焦于开发具有不同表面电荷的无胆固醇融合脂质体，旨在提高生物膜穿透能力。对脂质体的体外评估包括物理稳定性、生物相容性、与微生物细胞的融合以及穿透已形成生物膜的能力。使用动态光散射法发现，无胆固醇融合脂质体的尺寸小于200 nm，粒径分布窄（PDI < 0.1），在4℃储存时物理稳定性可达一年。透射电子显微镜（TEM）图像证实了所选脂质体制剂的囊泡大小。使用脂质混合和流式细胞仪检测评估脂质体与微生物细胞融合的能力。结果发现，无论脂质体电荷如何，与大肠杆菌的融合水平均高于金黄色葡萄球菌和白色念珠菌。中性脂质体表现出最高的融合率，其次分别是阳离子脂质体和阴离子脂质体。我们的研究表明，融合是一个多因素过程，受脂质体的化学成分、脂质体表面电荷以及微生物细胞包膜成分的影响。评估了具有不同表面电荷的脂质体在预先形成的金黄色葡萄球菌生物膜中的渗透和滞留情况。所有脂质体，无论表面电荷如何，都能够穿透并扩散通过生物膜基质。然而，阳离子脂质体表现出最大的相互作用和滞留。通过溶血和细胞毒性研究证实了生物相容性。本研究中开发的无胆固醇融合脂质体作为用于纳入抗菌剂进行生物膜治疗的药物递送系统显示出有前景的潜力。
