Optimization of the Technology for the Preparation of Cationic Liposomes for the Delivery of Nucleic Acids

Luneva, A. S.; Puchkov, Pavel A.; Shmendel, Elena V.; Zenkova, Marina A.; Kuzevanova, A. Yu.; Alimov, Andrei; Карпухин, А. В.; Маслов, М. А.

doi:10.1134/s1068162019010084

Cited by 10 publications

(2 citation statements)

References 17 publications

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“…All liposomal formulations were prepared via the hydrating thin lipid film method [ 27 ]. Briefly, a solution of the polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) [ 28 ] in a mixture of CHCl 3 -CH 3 OH (1:2 vol.)…”

Section: Methodsmentioning

confidence: 99%

Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA

Bishani,

Makarova,

Shmendel

et al. 2023

Pharmaceutics

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In this study, the impact of different delivery systems on the cytokine-inducing, antiproliferative, and antitumor activities of short immunostimulatory double-stranded RNA (isRNA) was investigated. The delivery systems, consisting of the polycationic amphiphile 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20 tetraazahexacosan tetrahydrochloride (2X3), and the lipid-helper dioleoylphosphatidylethanolamine (DOPE), were equipped with polyethylene glycol lipoconjugates differing in molecular weight and structure. The main findings of this work are as follows: (i) significant activation of MCP-1 and INF-α, β, and γ production in CBA mice occurs under the action of isRNA complexes with liposomes containing lipoconjugates with long PEG chains, while activation of MCP-1 and INF-γ, but not INF-α or β, was observed under the action of isRNA lipoplexes containing lipoconjugates with short PEG chains; (ii) a pronounced antiproliferative effect on B16 melanoma cells in vitro, as well as an antitumor and hepatoprotective effect in vivo, was induced by isRNA pre-complexes with non-pegylated liposomes, while complexes containing lipoconjugates with long-chain liposomes were inactive; (iii) the antitumor activity of isRNA correlated with the efficiency of its accumulation in the cells and did not explicitly depend on the activation of cytokine and interferon production. Thus, the structure of the delivery system plays a vital role in determining the response to isRNA and allows for the choice of a delivery system depending on the desired effect.

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Section: Methodsmentioning

confidence: 99%

Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA

Bishani,

Makarova,

Shmendel

et al. 2023

Pharmaceutics

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show abstract

“…All cationic liposomes were prepared via the hydrating thin lipid film method [62]. Briefly, a solution of 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) [63] or 1,30-bis(cholest-5-en-3β-yloxy-carbonylamino)-9,13,18,22-tetraaza-3,6,25,28-tetraoxatriacontane tetrahydrochloride (2X7) [55] in a mixture of CHCl 3 -CH 3 OH (5:1 vol.)…”

Section: Preparation Of Cationic Liposomesmentioning

confidence: 99%

Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues

Fedorovskiy,

Antropov,

Dome

et al. 2024

Pharmaceutics

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Over the past decade, mRNA-based therapy has displayed significant promise in a wide range of clinical applications. The most striking example of the leap in the development of mRNA technologies was the mass vaccination against COVID-19 during the pandemic. The emergence of large-scale technology and positive experience of mRNA immunization sparked the development of antiviral and anti-cancer mRNA vaccines as well as therapeutic mRNA agents for genetic and other diseases. To facilitate mRNA delivery, lipid nanoparticles (LNPs) have been successfully employed. However, the diverse use of mRNA therapeutic approaches requires the development of adaptable LNP delivery systems that can control the kinetics of mRNA uptake and expression in target cells. Here, we report effective mRNA delivery into cultured mammalian cells (HEK293T, HeLa, DC2.4) and living mouse muscle tissues by liposomes containing either 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) or the newly applied 1,30-bis(cholest-5-en-3β-yloxycarbonylamino)-9,13,18,22-tetraaza-3,6,25,28-tetraoxatriacontane tetrahydrochloride (2X7) cationic lipids. Using end-point and real-time monitoring of Fluc mRNA expression, we showed that these LNPs exhibited an unusually delayed (of over 10 h in the case of the 2X7-based system) but had highly efficient and prolonged reporter activity in cells. Accordingly, both LNP formulations decorated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) provided efficient luciferase production in mice, peaking on day 3 after intramuscular injection. Notably, the bioluminescence was observed only at the site of injection in caudal thigh muscles, thereby demonstrating local expression of the model gene of interest. The developed mRNA delivery systems hold promise for prophylactic applications, where sustained synthesis of defensive proteins is required, and open doors to new possibilities in mRNA-based therapies.

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Effects of spacers within a series of novel folate-containing lipoconjugates on the targeted delivery of nucleic acids

Shmendel

Kabilova

Морозова

et al. 2020

Journal of Drug Delivery Science and Technology

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Optimization of the Technology for the Preparation of Cationic Liposomes for the Delivery of Nucleic Acids

Cited by 10 publications

References 17 publications

Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA

Influence of the Composition of Cationic Liposomes on the Performance of Cargo Immunostimulatory RNA

Novel Efficient Lipid-Based Delivery Systems Enable a Delayed Uptake and Sustained Expression of mRNA in Human Cells and Mouse Tissues

Effects of spacers within a series of novel folate-containing lipoconjugates on the targeted delivery of nucleic acids

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