Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery.
Pharmaceutics
; 15(2)2023 Feb 01.
Article
in English
| MEDLINE | ID: covidwho-2281066
ABSTRACT
Lipid nanoparticles (LNPs) are the commonly used delivery tools for messenger RNA (mRNA) therapy and play an indispensable role in the success of COVID-19 mRNA vaccines. Ionizable cationic lipids are the most important component in LNPs. Herein, we developed a series of new ionizable lipids featuring bioreducible disulfide bonds, and constructed a library of lipids derived from dimercaprol. LNPs prepared from these ionizable lipids could be stored at 4 °C for a long term and are non-toxic toward HepG2 and 293T cells. In vivo experiments demonstrated that the best C4S18A formulations, which embody linoleoyl tails, show strong firefly luciferase (Fluc) mRNA expression in the liver and spleen via intravenous (IV) injection, or at the local injection site via intramuscular injection (IM). The newly designed ionizable lipids can be potentially safe and high-efficiency nanomaterials for mRNA therapy.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Topics:
Vaccines
Language:
English
Year:
2023
Document Type:
Article
Affiliation country:
Pharmaceutics15020477
Similar
MEDLINE
...
LILACS
LIS