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@ARTICLE{Ziller:418120,
author = {Ziller, Antje and Nogueira, Sara S. and Hühn, Eva and
Funari, Sergio de Souza and Brezesinski, Gerald and
Hartmann, Hermann and Sahin, Ugur and Haas, Heinrich and
Langguth, Peter},
title = {{I}ncorporation of m{RNA} in {L}amellar {L}ipid {M}atrices
for {P}arenteral {A}dministration},
journal = {Molecular pharmaceutics},
volume = {15},
number = {2},
issn = {1543-8392},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {PUBDB-2019-00207},
pages = {642 - 651},
year = {2018},
note = {© American Chemical Society},
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.},
cin = {DOOR / FS-PEX},
ddc = {610},
cid = {I:(DE-H253)HAS-User-20120731 / I:(DE-H253)FS-PEX-20130206},
pnm = {6215 - Soft Matter, Health and Life Sciences (POF3-621)},
pid = {G:(DE-HGF)POF3-6215},
experiment = {EXP:(DE-H253)D-A2-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29232147},
UT = {WOS:000424730900030},
doi = {10.1021/acs.molpharmaceut.7b01022},
url = {https://bib-pubdb1.desy.de/record/418120},
}