Journal Article

PUBDB-2019-00207

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Incorporation of mRNA in Lamellar Lipid Matrices for Parenteral Administration

Ziller, A. ; Nogueira, S. S. ; Hühn, E. ; Funari, S. d. S.DESY* ; Brezesinski, G. ; Hartmann, H. ; Sahin, U. ; Haas, H. ; Langguth, P. (Corresponding author)

2018
American Chemical Society Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.molpharmaceut.7b01022  doi:10.3204/PUBDB-2019-00207

Abstract: Insertion of high molecular weight messenger RNA (mRNA) into lyotropic lipid phases as model systems for controlled release formulations for the mRNA was investigated. Low fractions of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were used as an anchor to load the mRNA into a lamellar lipid matrix. Dispersions of zwitterionic lipid in the aqueous phase in the presence of increasing fractions of mRNA and cationic lipid were prepared, and the molecular organization was investigated as a function of mRNA and cationic lipid fraction. Insertion of both cationic lipid and mRNA was clearly proven from the physicochemical characteristics. The d-spacing of the lipid bilayers, as determined by small-angle X-ray scattering (SAXS) measurements, responded sensitively to the amount of inserted DOTAP and mRNA. A concise model of the insertion of the mRNA in the lipid matrices was derived, indicating that the mRNA was accommodated in the aqueous slab between lipid bilayers. Depending on the DOTAP and mRNA fraction, a different excess of water was present in this slab. Results from further physicochemical characterization, including determination of free and bound mRNA, zeta potential, and calorimetry data, were in line with this assumption. The structure of these concentrated lipid/mRNA preparations was maintained upon dilution. The functionality of the inserted mRNA was proven by cell culture experiments using C2C12 murine myoblast cells with the luciferase-encoding mRNA. The described lipid phases as carriers for the mRNA may be applicable for different routes of local administration, where control of the release kinetics and the form of the released mRNA (bound or free) is required.

Note: © American Chemical Society

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Contributing Institute(s):

1. DOOR-User (DOOR)
2. PETRA III Extension (FS-PEX)

Research Program(s):

1. 6215 - Soft Matter, Health and Life Sciences (POF3-621) (POF3-621)

Experiment(s):

1. DORIS Beamline A2 (DORIS III)

Appears in the scientific report 2018

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Database coverage:
; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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