Molecular localization and exchange kinetics in pharmaceutical liposome and mRNA lipoplex nanoparticle products determined by small angle X-ray scattering and pulsed field gradient NMR diffusion measurements.
Eur J Pharm Biopharm
; 201: 114380, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38960290
ABSTRACT
We have used pulsed field gradient (PFG)-NMR diffusion experiments, also known as DOSY, in combination with small angle X-ray scattering measurements to investigate structure and molecular exchange dynamics between pharmaceutical lipid nanoparticles and the bulk phase. Using liposomes and lipoplexes formed after complexation of the liposomes with messenger mRNA as test systems, information on dynamics of encapsulated water molecules, lipids and excipients was obtained. The encapsulated fraction, having a diffusivity similar to that of the liposomes, could be clearly identified and quantified by the NMR diffusion measurements. The unilamellar liposome membranes allowed a fast exchange of water molecules, while sucrose, used as an osmolyte and model solute, showed very slow exchange. Upon interactions with mRNA a topological transition from a vesicular to a lamellar organization took place, where the mRNA was inserted in repeating lipid bilayer stacks. In the lipoplexes, a small fraction of tightly bound water molecules was present, with a diffusivity that was influenced by the additional presence of sucrose. This extended information on dynamic coherencies inside pharmaceutical nanoparticle products, provided by the combined application of SAXS and PFG-NMR diffusion measurements, can be valuable for evaluation of quality and comparability of nanoscaled pharmaceuticals.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Difracción de Rayos X
/
ARN Mensajero
/
Espectroscopía de Resonancia Magnética
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Dispersión del Ángulo Pequeño
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Nanopartículas
/
Liposomas
Idioma:
En
Revista:
Eur J Pharm Biopharm
Asunto de la revista:
FARMACIA
/
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Países Bajos