Evolution of the structure of lipid nanoparticles for nucleic acid delivery: From in situ studies of formulation to colloidal stability
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Evolution of the structure of lipid nanoparticles for nucleic acid delivery : From in situ studies of formulation to colloidal stability. / Gilbert, Jennifer; Sebastiani, Federica; Arteta, Marianna Yanez; Terry, Ann; Fornell, Anna; Russell, Robert; Mahmoudi, Najet; Nylander, Tommy.
In: Journal of Colloid and Interface Science, Vol. 660, 2024, p. 66-76.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Evolution of the structure of lipid nanoparticles for nucleic acid delivery
T2 - From in situ studies of formulation to colloidal stability
AU - Gilbert, Jennifer
AU - Sebastiani, Federica
AU - Arteta, Marianna Yanez
AU - Terry, Ann
AU - Fornell, Anna
AU - Russell, Robert
AU - Mahmoudi, Najet
AU - Nylander, Tommy
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2024
Y1 - 2024
N2 - The development of lipid nanoparticle (LNP) based therapeutics for delivery of RNA has triggered the advance of new strategies for formulation, such as high throughput microfluidics for precise mixing of components into well-defined particles. In this study, we have characterised the structure of LNPs throughout the formulation process using in situ small angle x-ray scattering in the microfluidic chip, then by sampling in the subsequent dialysis process. The final formulation was investigated with small angle x-ray (SAXS) and neutron (SANS) scattering, dynamic light scattering (DLS) and cryo-TEM. The effect on structure was investigated for LNPs with a benchmark lipid composition and containing different cargos: calf thymus DNA (DNA) and two model mRNAs, polyadenylic acid (polyA) and polyuridylic acid (polyU). The LNP structure evolved during mixing in the microfluidic channel, however was only fully developed during the dialysis. The colloidal stability of the final formulation was affected by the type of incorporated nucleic acids (NAs) and decreased with the degree of base-pairing, as polyU induced extensive particle aggregation. The main NA LNP peak in the SAXS data for the final formulation were similar, with the repeat distance increasing from polyU
AB - The development of lipid nanoparticle (LNP) based therapeutics for delivery of RNA has triggered the advance of new strategies for formulation, such as high throughput microfluidics for precise mixing of components into well-defined particles. In this study, we have characterised the structure of LNPs throughout the formulation process using in situ small angle x-ray scattering in the microfluidic chip, then by sampling in the subsequent dialysis process. The final formulation was investigated with small angle x-ray (SAXS) and neutron (SANS) scattering, dynamic light scattering (DLS) and cryo-TEM. The effect on structure was investigated for LNPs with a benchmark lipid composition and containing different cargos: calf thymus DNA (DNA) and two model mRNAs, polyadenylic acid (polyA) and polyuridylic acid (polyU). The LNP structure evolved during mixing in the microfluidic channel, however was only fully developed during the dialysis. The colloidal stability of the final formulation was affected by the type of incorporated nucleic acids (NAs) and decreased with the degree of base-pairing, as polyU induced extensive particle aggregation. The main NA LNP peak in the SAXS data for the final formulation were similar, with the repeat distance increasing from polyU
U2 - 10.1016/j.jcis.2023.12.165
DO - 10.1016/j.jcis.2023.12.165
M3 - Journal article
C2 - 38241872
AN - SCOPUS:85182743795
VL - 660
SP - 66
EP - 76
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
SN - 0021-9797
ER -
ID: 381495405