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• W4210784945 abstract "Lipid nanoparticles (LNPs) mediated mRNA delivery has gained prominence due to the success of mRNA vaccines against Covid-19, without which it would not have been possible. However, there is little clinical validation of this technology for other mRNA-based therapeutic approaches. Systemic administration of LNPs predominantly targets the liver, but delivery to other organs remains a challenge. Local approaches remain a viable option for some disease indications, such as Cystic Fibrosis, where aerosolized delivery to airway epithelium is the preferred route of administration. With this in mind, novel cationic lipids (L1-L4) have been designed, synthesized and co-formulated with a proprietary ionizable lipid. These LNPs were further nebulized, along with baseline control DOTAP-based LNP (DOTAP+), and tested in vitro for mRNA integrity and encapsulation efficiency, as well as transfection efficiency and cytotoxicity in cell cultures. Improved biodegradability and potentially superior elimination profiles of L1-L4, in part due to physicochemical characteristics of putative metabolites, are thought to be advantageous for prospective therapeutic lung delivery applications using these lipids." @default.
• W4210784945 created "2022-02-08" @default.
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• W4210784945 date "2022-03-01" @default.
• W4210784945 modified "2023-09-25" @default.
• W4210784945 title "Synthesis and bioactivity of readily hydrolysable novel cationic lipids for potential lung delivery application of mRNAs" @default.
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• W4210784945 doi "https://doi.org/10.1016/j.chemphyslip.2022.105178" @default.
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