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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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Formulation, Characterization, and In Vitro/In Vivo Efficacy Studies of a Novel Liposomal Drug Delivery System of Amphiphilic Jaspine B for Treatment of Synovial Sarcoma
Sphingomyelin is a cell membrane sphingolipid that is upregulated in synovial sarcoma (SS). Jaspine B has been shown to inhibit sphingomyelin synthase, which synthesizes sphingomyelin from ceramide, a critical signal transducer; however, jaspine B’s low bioavailability limits its application as a promising treatment option. To address this shortcoming, we used microfluidics to develop a liposomal delivery system with increased anticancer efficacy. The nano-liposome size was determined by transmission electron microscopy. The jaspine B liposome was tested for its tumor inhibitory efficacy compared to plain jaspine B in in vitro and in vivo studies. The human SS cell line was tested for cell viability using varying jaspine B concentrations. In a mouse model of SS, tumor growth suppression was evaluated during four weeks of treatment (3 times/week). The results show that jaspine B was successfully formulated in the liposomes with a size ranging from 127.5 ± 61.2 nm. The MTT assay and animal study results indicate that jaspine B liposomes dose-dependently lowers cell viability in the SS cell line and effectively suppresses tumor cell growth in the SS animal model. The novel liposome drug delivery system addresses jaspine B’s low bioavailability issues and improves its therapeutic efficacy.
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- Award ID(s):
- 2019074
- PAR ID:
- 10350583
- Date Published:
- Journal Name:
- Marine Drugs
- Volume:
- 20
- Issue:
- 8
- ISSN:
- 1660-3397
- Page Range / eLocation ID:
- 509
- 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/10.3390/md20080509
