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Hybrid Lipid Nanocapsules: A Robust Platform for mRNA Delivery.

Sunil Kumar YadavaB Pradeep Kumar ReddyMark R PrausnitzMarcus T Cicerone
Published in: ACS applied materials & interfaces (2024)
The success of the mRNA vaccine against COVID-19 has garnered significant interest in the development of mRNA therapeutics against other diseases, but there remains a strong need for a stable and versatile delivery platform for these therapeutics. In this study, we report on a family of robust hybrid lipid nanocapsules (hLNCs) for the delivery of mRNA. The hLNCs are composed of kolliphore HS15, labrafac lipophile WL1349, 1,2-dioleoyl- sn -glycero-3-phosphoethanolamine (DOPE), and a conjugate of oleic acid (OA) and polyethylenimines of varying size (PEI─0.8, 1.8, and 25 kDa). They are prepared by a solvent-free, temperature-phase inversion method, yielding an average size of ∼40 nm and a particle distribution index (PDI) < 0.2. We demonstrate that the PDI remains <0.2 over a wide pH range and in a wide range of medium. We further show that the PDI and the functionality of mRNA condensed on the particles are robust to drying in a sugar glass and subsequent rehydration. Finally, we demonstrate that mRNA-loaded hLNCs yield reasonable transfection in vitro and in vivo settings.
Keyphrases
  • binding protein
  • sars cov
  • coronavirus disease
  • high throughput
  • magnetic resonance imaging
  • cancer therapy
  • drug delivery
  • heat shock protein
  • single cell