Meikle Thomas G, Dharmadana Durga, Hoffmann Søren V, Jones Nykola C, Drummond Calum J, Conn Charlotte E
RMIT University, School of Science, College of Science Engineering and Health, 124 La Trobe Street, Melbourne, Victoria 3000, Australia.
ISA, Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, DK-8000 Aarhus C, Denmark.
J Colloid Interface Sci. 2021 Apr;587:90-100. doi: 10.1016/j.jcis.2020.11.124. Epub 2020 Dec 2.
The growing global threat of antimicrobial resistance, combined with the slowed development of novel antibiotics, has resulted in a critical need for new antimicrobial therapies. Naturally occurring antimicrobial peptides (AMPs) can act as highly potent, broad-spectrum antibiotics which may be less likely to engender resistance in target organisms. However, their susceptibility to proteolysis and lack of specificity necessitates the use of a drug delivery vehicle to both protect the AMP from chemical degradation and provide a platform for further functionalization, enabling the development of targeted delivery and release systems. In this study, we have used lipid-based inverse bicontinuous cubic phase nanoparticles (cubosomes) as delivery vehicles for six different antimicrobial peptides. The phase stability, morphology, and peptide loading efficiency of the nanoparticles were characterized and rationalized according to lipid composition, buffer conditions, as well as peptide charge and hydrophobicity. The AMP loading efficiency within cubosomes was increased significantly through simple manipulation of electrostatic charge. Minimum inhibitory concentration (MIC) values were determined for formulations with high loading efficiency against Staphylococcus aureus, Bacilus cereus, Escherichia coli, and Pseudomonas aeruginosa. Encapsulation within a lipid nanocarrier was shown to increase antimicrobial activity for some formulations. We anticipate that the further development of these peptide loaded cubosomes will enable the design of potent and targeted antibiotic therapies.
全球对抗菌素耐药性的威胁日益增加，加上新型抗生素研发速度放缓，导致对新型抗菌疗法的迫切需求。天然存在的抗菌肽（AMPs）可作为高效、广谱抗生素，在靶标生物体中产生耐药性的可能性较小。然而，它们易受蛋白水解作用影响且缺乏特异性，因此需要使用药物递送载体来保护AMPs免受化学降解，并提供进一步功能化的平台，从而实现靶向递送和释放系统的开发。在本研究中，我们使用基于脂质的反相双连续立方相纳米颗粒（立方液晶纳米粒）作为六种不同抗菌肽的递送载体。根据脂质组成、缓冲条件以及肽的电荷和疏水性，对纳米颗粒的相稳定性、形态和肽负载效率进行了表征和合理化分析。通过简单的静电荷操纵，显著提高了立方液晶纳米粒内的AMPs负载效率。测定了高负载效率制剂对金黄色葡萄球菌、蜡样芽孢杆菌、大肠杆菌和铜绿假单胞菌的最低抑菌浓度（MIC）值。结果表明，对于某些制剂，封装在脂质纳米载体中可增强抗菌活性。我们预计，这些负载肽的立方液晶纳米粒的进一步开发将有助于设计出高效且靶向的抗生素疗法。
