Cyanuric chloride as the basis for compositionally diverse lipids

Nardo, David; Akers, Caleb; Cheung, Nicholas E; Isom, Cierra M; Spaude, Jason T; Pack, Daniel W.; Venditto, Vincent J.

doi:10.1039/d1ra02425f

Cited by 4 publications

(6 citation statements)

References 34 publications

(59 reference statements)

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“…The toxicity of TZ9 in vivo was unexpected as in vitro studies, published previously, indicated TZ9 to be less toxic than TZ3. 12 The discordant results between in vitro and in vivo studies suggest that the cause of toxicity is more complex than simple cytotoxicity; however, the exact physiologic mechanism of toxicity remains unclear. Based on the exposure-induced increase in a limited number of toxicity indicators and the visual inspection of some of the mice, it seems likely that a multi-system inflammatory response occurred following i.p.…”

Section: Resultsmentioning

confidence: 99%

“…10,11 Building upon these data, we previously reported the synthesis of a novel class of triazine (TZ) lipids, based on cyanuric chloride, that demonstrate potential for nucleic acid delivery due to the aromatic linker with appended cationic moieties. 12 Like the dimerizable, redox-sensitive lipids reported by Candiani et al and the compounds published recently by Pennetta et al, these lipids show strong potential for gene delivery. 13,14 The leading cationic and ionizable lipids for gene delivery have been further optimized by including them in specific formulations containing helper lipids (e.g.…”

Section: Introductionmentioning

confidence: 93%

“…Two triazine lipids that previously demonstrated efficacy in vitro (triazine lipids 3 and 9, or TZ3 and TZ9) 12 were first evaluated for their in vivo toxicity before analysing their transfection efficiency. Groups of male and female C57BL/6J mice were administered TZ LNPs at 10 and 20 mM intraperitoneally (i.p.)…”

Section: In Vivo Toxicity Of Tz Lipidsmentioning

confidence: 99%

“…58,59 In vivo transfection with GFP plasmid Upon optimization of a LNP formulation containing PEG550 and DOPE, 10 µg of GFP plasmid was delivered to BALB/c mice via either LNP or our previously reported LPs made with a 1 : 1 TZ3 : DOPE ratio and compared to AAV8 delivery at 2 × 10 9 GC per mouse. 12 The LNPs were over 200 nm in diameter (Table S1 †) and non-PEGylated formulations exhibited a propensity to aggregate, so delivery was made by i.p. injection to prevent potential harm to the animals from particle aggregation after intravenous (i.v.)…”

Section: In Vitro Optimization Of Lnp Formulation Using Gfp Plasmidmentioning

confidence: 99%

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In vivoassessment of triazine lipid nanoparticles as transfection agents for plasmid DNA

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: In Vivo Toxicity Of Tz Lipidsmentioning

confidence: 99%

Section: In Vitro Optimization Of Lnp Formulation Using Gfp Plasmidmentioning

confidence: 99%

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In vivoassessment of triazine lipid nanoparticles as transfection agents for plasmid DNA

et al. 2022

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“…All liposomal formulations were prepared by thin film hydration according to an established protocol ( Nardo et al, 2021 ). Briefly, phospholipids and cholesterol solutions were mixed in a round bottom glass tube at the desired molar ratio.…”

Section: Methodsmentioning

confidence: 99%

Optimization and Characterization of a Liposomal Azithromycin Formulation for Alternative Macrophage Activation

Masud

Alsharif

Creameans

et al. 2022

Front. Drug. Deliv.

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Liposomal azithromycin (L-AZM) promotes macrophage polarization toward an M2-like phenotype in the context of myocardial infarction that results in improved cardiovascular outcomes in mice. To improve upon this formulation, we sought to identify optimized formulation, stability, and biological activity parameters necessary to enhance the immunomodulatory activity and efficacy of L-AZM. While our parent formulation contains a mixture of long-chain saturated phosphatidylcholine and phosphatidylglycerol lipids, we evaluated a series of formulations with different amounts of unsaturated lipids and cholesterol with the goal of improving the loading capacity and stability of the formulations. We also introduce fusogenic lipids to improve the cytosolic delivery to enhance the immune modulatory properties of the drug. To achieve these goals, we initially prepared a library of 24 formulations using thin film hydration and assessed the resultant liposomes for size and polydispersity. Five lead formulations were identified based on low polydispersity (<0.3) and stability over time. The lead formulations were then evaluated for stability in serum using dialysis and macrophage polarization activity in vitro as measured by decreased IL-12 expression. Collectively, our data indicate that the formulation components drive the balance between encapsulation efficiency and stability and that all the lead liposomal formulations improve in vitro alternative macrophage activation as compared to free AZM.

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Development of Tris‐(triazolyl)‐s–triazine Linker‐Based Cationic Amphiphiles: Stability and Gene Delivery Applications

Manturthi,

Narayan,

Patri

2023

ChemistrySelect

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The ability to readily be designed, manufactured, and described has made cationic lipids one of the highly adaptable vehicles for the transfer of DNA, RNA, and numerous additional therapeutic compounds. In this article, we synthesized a variety of Tris‐(triazolyl)‐s‐triazine linker‐based cationic lipids with different types of anchoring groups, and assessed the transfection efficacy. Specifically, two identical tails like either two alpha‐tocopherol domains or cholesterol domains or aliphatic chains (saturated), and on the other hand, two different tails, alpha‐tocopherol domain and cholesterol domain or alpha‐tocopherol domain and aliphatic chain (saturated) were employed as hydrophobic motifs to synthesize the cationic lipids. The stability, size, and surface charge of liposomes were performed by dynamic light scattering technique. Cytotoxicity study on cell survival showed that the synthesized lipids are less hazardous to the cells despite the fact that cationic lipids have large molecular structure. The lipid having di alpha‐tocopherol domains demonstrated phenomenal β‐galactosidase protein expression and enhanced green fluorescence expression in the hepatocellular carcinoma cell line. Findings from the physico‐chemical and biological evaluations the developed lipids are compatible in various forms while maintaining low cytotoxicity and efficient carriers for nucleic acid delivery.

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Cyanuric chloride as the basis for compositionally diverse lipids

Abstract: Cyanuric chloride enables facile synthesis of lipids with unique biophysical properties for use in gene and vaccine delivery.

Cited by 4 publications

References 34 publications

In vivoassessment of triazine lipid nanoparticles as transfection agents for plasmid DNA

In vivoassessment of triazine lipid nanoparticles as transfection agents for plasmid DNA

Optimization and Characterization of a Liposomal Azithromycin Formulation for Alternative Macrophage Activation

Development of Tris‐(triazolyl)‐s–triazine Linker‐Based Cationic Amphiphiles: Stability and Gene Delivery Applications

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