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Abstract Liposomes are lipid‐based nanoparticles that have been used to deliver encapsulated drugs for a variety of applications, including treatment of life‐threatening fungal infections. By understanding the effect of composition on liposome interactions with both fungal and mammalian cells, new effective antifungal liposomes can be developed. In this study, we investigated the impact of lipid saturation and cholesterol content on fungal and mammalian cell interactions with liposomes. We used three phospholipids with different saturation levels (saturated hydrogenated soy phosphatidylcholine (HSPC), mono‐unsaturated 1‐palmitoyl‐2‐oleoyl‐glycero‐3‐phosphocholine (POPC), and di‐unsaturated 1‐palmitoyl‐2‐linoleoyl‐sn‐glycero‐3‐phosphocholine (PLPC)) and cholesterol concentrations ranging from 15% to 40% (w/w) in our liposome formulations. Using flow cytometry, >80% ofCandida albicansSC5314 cells were found to interact with all liposome formulations developed, while >50% of clinical isolates tested exhibited interaction with these liposomes. In contrast, POPC‐containing formulations exhibited low levels of interaction with murine fibroblasts and human umbilical vein endothelial cells (<30%), while HSPC and PLPC formulations had >50% and >80% interaction, respectively. Further, PLPC formulations caused a significant decrease in mammalian cell viability. Formulations that resulted in low levels of mammalian cell interaction, minimal cytotoxicity, and high levels of fungal cell interaction were then used to encapsulate the antifungal drug, amphotericin B. These liposomes eradicated planktonicC. albicansat drug concentrations lower than free drug, potentially due to the high levels of liposome‐C. albicansinteraction. Overall, this study provides new insights into the design of liposome formulations towards the development of new antifungal therapeutics.
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Molecular interactions of phospholipid monolayers with a model phospholipase
The intrinsic overexpression of secretory phospholipase A2 (sPLA 2 ) in various pro-inflammatory diseases and cancers has the potential to be exploited as a therapeutic strategy for diagnostics and treatment. To explore this potential and advance our knowledge of the role of sPLA 2 in related diseases, it is necessary to systematically investigate the molecular interaction of the enzyme with lipids. By employing a Langmuir trough integrated with X-ray reflectivity and grazing incidence X-ray diffraction techniques, this study examined the molecular packing structure of 1,2-palmitoyl- sn-glycero -3-phosphocholine (DPPC) films before and after enzyme adsorption and enzyme-catalyzed degradation. Molecular interaction of sPLA 2 (from bee venom) with the DPPC monolayer exhibited Ca 2+ dependence. DPPC molecules at the interface without Ca 2+ retained a monolayer organization; upon adsorption of sPLA 2 to the monolayer the packing became tighter. In contrast, sPLA 2 -catalyzed degradation of DPPC occurred in the presence of Ca 2+ , leading to disruption of the ordered monolayer structure of DPPC. The interfacial film became a mixture of highly ordered multilayer domains of palmitic acid (PA) and loosely packed monolayer phase of 1-palmitoyl-2-hydroxy- sn-glycero -3-phosphocholine (lysoPC) that potentially contained the remaining un-degraded DPPC. The redistribution of lipid degradation products into the third dimension, which produced multilayer PA domains, damaged the structural integrity of the original lipid layer and may explain the bursting of liposomes observed in other studies after a latency period of mixing liposomes with sPLA 2 . A quantitative understanding of the lipid packing and lipid-enzyme interaction provides an intuitive means of designing and optimizing lipid-related drug delivery systems.
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- Award ID(s):
- 1834750
- PAR ID:
- 10135132
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 15
- Issue:
- 20
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 4068 to 4077
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/C8SM01154K
