Inhalable dry powder product (DPP) of mRNA lipid nanoparticles (LNPs) for pulmonary delivery.

Autor: Sarode A; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA., Patel P; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA., Vargas-Montoya N; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA., Allawzi A; Translate Bio, Lexington, MA, USA., Zhilin-Roth A; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA., Karmakar S; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA., Boeglin L; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA., Deng H; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA., Karve S; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA. shri.karve@sanofi.com., DeRosa F; mRNA Center of Excellence, 200 West Street, MA, 02451, Sanofi Waltham, USA.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 Feb; Vol. 14 (2), pp. 360-372. Date of Electronic Publication: 2023 Aug 01.
DOI: 10.1007/s13346-023-01402-y
Abstrakt: Pulmonary delivery of mRNA via inhalation is a very attractive approach for RNA-based therapy for treatment of lung diseases. In this work, we have demonstrated successful development of an mRNA-lipid nanoparticle (LNP) dry powder product (DPP), wherein the LNPs were spray dried using hydroalcoholic solvent along with mannitol and leucine as excipients. The desired critical attributes for the DPP were accomplished by varying the excipients, lipid composition, concentration of LNPs, and weight percentage of mRNA. Leucine alone or in combination with mannitol improved the formulation by increasing the mRNA yield as well as decreasing the particle size. Intratracheal administration of the DPP in mice resulted in luciferase expression in the trachea and lungs indicating successful delivery of functional mRNA. Our results show formulation optimization of mRNA LNPs administered in the form of DPP results in an efficacious functional delivery with great promise for future development of mRNA therapeutics for lung diseases.
(© 2023. The Author(s).)
Databáze: MEDLINE
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