Synthesis and bioactivity of readily hydrolysable novel cationic lipids for potential lung delivery application of mRNAs.
Chem Phys Lipids
; 243: 105178, 2022 03.
Article
in English
| MEDLINE | ID: covidwho-1664753
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
RNA, Messenger
/
Nanoparticles
/
Liposomes
/
Lung
Type of study:
Observational study
/
Prognostic study
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Chem Phys Lipids
Year:
2022
Document Type:
Article
Affiliation country:
J.chemphyslip.2022.105178
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