Exploring the impact of physicochemical properties of liposomal formulations on their in vivo fate

Sheikholeslami, Behjat; Lam, Nga Wing; Dua, Kamal; Haghi, Mehra

doi:10.1016/j.lfs.2022.120574

Cited by 47 publications

(28 citation statements)

References 240 publications

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“…Saturated lipids have greater packing efficiency compared to unsaturated lipids, resulting in increased rigidity. 10,11 Further, increasing CHOL concentrations decreases rigidity for saturated lipids and increases rigidity for unsaturated lipids due to changes in the lipid molecular packing efficiency. 13,43,44 The interplay between lipid saturation and CHOL were confirmed with our laurdan studies for all liposome formulations (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

“…Cholesterol (CHOL), a common component included in many liposome formulations, has also been shown to alter membrane fluidity and liposome stability by affecting lipid packing within the bilayers 12–14 . Liposome properties including charge and fluidity, which are tightly linked to composition, in turn can affect how liposomes interact with various cell types including association with cell membranes and cellular uptake 11,15–17 . Studies investigating the effects of liposome composition on cellular interactions have focused primarily on mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

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Antifungal liposomes: Lipid saturation and cholesterol concentration impact interaction with fungal and mammalian cells

LaMastro

Campbell

Gonzalez

et al. 2023

J Biomedical Materials Res

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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% of Candida albicans SC5314 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 planktonic C. albicans at drug concentrations lower than free drug, potentially due to the high levels of liposome‐C. albicans interaction. Overall, this study provides new insights into the design of liposome formulations towards the development of new antifungal therapeutics.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antifungal liposomes: Lipid saturation and cholesterol concentration impact interaction with fungal and mammalian cells

LaMastro

Campbell

Gonzalez

et al. 2023

J Biomedical Materials Res

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“…One caveat of our study is that we have yet to determine which factor(s) cause the increasing size and charges of liposome‐EV‐KRAS when compared with liposomes alone. The factor(s) could be from EV‐KRAS complex derived or unidentified factors (Sani et al., 2022 , Sheikholeslami et al., 2022 ) including aggregation (Dhiman et al., 2022 ). Future work is needed to identify the involved factor(s).…”

Section: Discussionmentioning

confidence: 99%

An extracellular vesicular mutant KRAS‐associated protein complex promotes lung inflammation and tumor growth

Sriwastva

Teng

et al. 2023

J of Extracellular Vesicle

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Extracellular vesicles (EVs) contain more than 100 proteins. Whether there are EVs proteins that act as an ‘organiser’ of protein networks to generate a new or different biological effect from that identified in EV‐producing cells has never been demonstrated. Here, as a proof‐of‐concept, we demonstrate that EV‐G12D‐mutant KRAS serves as a leader that forms a protein complex and promotes lung inflammation and tumour growth via the Fn1/IL‐17A/FGF21 axis. Mechanistically, in contrast to cytosol derived G12D‐mutant KRAS complex from EVs‐producing cells, EV‐G12D‐mutant KRAS interacts with a group of extracellular vesicular factors via fibronectin‐1 (Fn1), which drives the activation of the IL‐17A/FGF21 inflammation pathway in EV recipient cells. We show that: (i), depletion of EV‐Fn1 leads to a reduction of a number of inflammatory cytokines including IL‐17A; (ii) induction of IL‐17A promotes lung inflammation, which in turn leads to IL‐17A mediated induction of FGF21 in the lung; and (iii) EV‐G12D‐mutant KRAS complex mediated lung inflammation is abrogated in IL‐17 receptor KO mice. These findings establish a new concept in EV function with potential implications for novel therapeutic interventions in EV‐mediated disease processes.

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“…Liposomes are a new therapeutic formulation capable of targeted drug delivery [ 75 , 76 , 77 ]. One of the main chemical components of liposomes is a phospholipid, among which the most representative phospholipid is lecithin.…”

Section: Sirna Nanocarriersmentioning

confidence: 99%

Research Status and Prospect of Non-Viral Vectors Based on siRNA: A Review

Tong

Liu

Cao

et al. 2023

IJMS

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Gene therapy has attracted much attention because of its unique mechanism of action, non-toxicity, and good tolerance, which can kill cancer cells without damaging healthy tissues. siRNA-based gene therapy can downregulate, enhance, or correct gene expression by introducing some nucleic acid into patient tissues. Routine treatment of hemophilia requires frequent intravenous injections of missing clotting protein. The high cost of combined therapy causes most patients to lack the best treatment resources. siRNA therapy has the potential of lasting treatment and even curing diseases. Compared with traditional surgery and chemotherapy, siRNA has fewer side effects and less damage to normal cells. The available therapies for degenerative diseases can only alleviate the symptoms of patients, while siRNA therapy drugs can upregulate gene expression, modify epigenetic changes, and stop the disease. In addition, siRNA also plays an important role in cardiovascular diseases, gastrointestinal diseases, and hepatitis B. However, free siRNA is easily degraded by nuclease and has a short half-life in the blood. Research has found that siRNA can be delivered to specific cells through appropriate vector selection and design to improve the therapeutic effect. The application of viral vectors is limited because of their high immunogenicity and low capacity, while non-viral vectors are widely used because of their low immunogenicity, low production cost, and high safety. This paper reviews the common non-viral vectors in recent years and introduces their advantages and disadvantages, as well as the latest application examples.

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Exploring the impact of physicochemical properties of liposomal formulations on their in vivo fate

Cited by 47 publications

References 240 publications

Antifungal liposomes: Lipid saturation and cholesterol concentration impact interaction with fungal and mammalian cells

Antifungal liposomes: Lipid saturation and cholesterol concentration impact interaction with fungal and mammalian cells

An extracellular vesicular mutant KRAS‐associated protein complex promotes lung inflammation and tumor growth

Research Status and Prospect of Non-Viral Vectors Based on siRNA: A Review

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