Spray dried lipid nanoparticle formulations enable intratracheal delivery of mRNA.

Autor: Friis KP; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden. Electronic address: Kristina.Friis@astrazeneca.com., Gracin S; Inhalation Product Development, Pharmaceutical Technology & Development, Operations, AstraZeneca, Gothenburg, Sweden., Oag S; Animal Sciences & Technology, Clinical Pharmacology and Safety Sciences, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Leijon A; R&I Safety, Clinical Pharmacology and Safety Sciences, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Sand E; Imaging and Data Analytics, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Lindberg B; Bioscience Cough & In Vivo, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, Sweden., Lázaro-Ibáñez E; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Gothenburg, Sweden., Lindqvist J; CPSS Discovery Bioanalysis Europe, AstraZeneca, Gothenburg, Sweden., Whitehead KA; Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, United States of America., Bak A; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, AstraZeneca, Boston, United States of America.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2023 Nov; Vol. 363, pp. 389-401. Date of Electronic Publication: 2023 Sep 30.
DOI: 10.1016/j.jconrel.2023.09.031
Abstrakt: RNA therapies have recently taken a giant leap forward with the approval of Onpattro™, a siRNA therapy delivered using a lipid nanoparticle (LNP), and the LNP-enabled mRNA vaccines against COVID-19, which are the first mRNA drugs to reach the marketplace. The latter medicines have illustrated that stability is a significant challenge in the distribution of RNA drugs using non-viral delivery systems, particularly in areas without cold chain storage. Here, we describe a proof-of-concept study on the engineering of an LNP mRNA formulation suitable for spray drying. This process produced a dry powder formulation that maintained stability and preserved mRNA functionality with increased performance compared to liquid formulations stored two weeks at 4 °C. Intratracheal delivery of spray dried LNPs loaded with eGFP mRNA to rats resulted in the production of the eGFP protein in a range of cell types including bronchiolar epithelial cells, macrophages and type II pneumocytes; cell types involved in adaptive immunity and which would be valuable targets for inhaled vaccines against respiratory pathogens. Together, these data show that spray drying of LNPs enhances their stability and may enable RNA delivery to the lung for protein replacement therapy, gene editing, vaccination, and beyond.
Competing Interests: Declaration of Competing Interest KPF, SG, SO, AL, ES, BL, ELI, JL, AB are employed by AstraZeneca R&D, Gothenburg & Boston. KAW is an inventor on U.S. Patents 9,439,968 and 9,227,917, which are related to the materials described here.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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