Delivery of RNA to the Blood-Brain Barrier Endothelium Using Cationic Bicelles

Joan Cheng, Lushan Wang, Vineetha Guttha, Greg Haugstad, Karunya k. Kandimalla

Research output: Contribution to journalArticlepeer-review


Blood-brain barrier (BBB) dysfunction is prevalent in Alzheimer’s disease and other neurological disorders. Restoring normal BBB function through RNA therapy is a potential avenue for addressing cerebrovascular changes in these disorders that may lead to cognitive decline. Although lipid nanoparticles have been traditionally used as drug carriers for RNA, bicelles have been emerging as a better alternative because of their higher cellular uptake and superior transfection capabilities. Cationic bicelles composed of DPPC/DC7PC/DOTAP at molar ratios of 63.8/25.0/11.2 were evaluated for the delivery of RNA in polarized hCMEC/D3 monolayers, a widely used BBB cell culture model. RNA-bicelle complexes were formed at five N/P ratios (1:1 to 5:1) by a thin-film hydration method. The RNA-bicelle complexes at N/P ratios of 3:1 and 4:1 exhibited optimal particle characteristics for cellular delivery. The cellular uptake of cationic bicelles laced with 1 mol% DiI-C18 was confirmed by flow cytometry and confocal microscopy. The ability of cationic bicelles (N/P ratio 4:1) to transfect polarized hCMEC/D3 with FITC-labeled control siRNA was tested vis-a-vis commercially available Lipofectamine RNAiMAX. These studies demonstrated the higher transfection efficiency and greater potential of cationic bicelles for RNA delivery to the BBB endothelium.

Original languageEnglish (US)
Article number2086
Issue number8
StatePublished - Aug 2023

Bibliographical note

Funding Information:
Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nanotechnology Coordinated Infrastructure (NNCI) under Award Number ECCS-2025124. Portions of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC (Award Number DMR-2011401) and the NNCI (Award Number ECCS-2025124) programs.

Funding Information:
This research was funded by the National Institutes of Health/National Institute of Neurological Disorders and Stroke, grant number R01NS125437.

Publisher Copyright:
© 2023 by the authors.


  • Alzheimer’s disease
  • blood-brain barrier
  • cationic bicelles
  • drug delivery
  • inflammation
  • lipid nanodiscs
  • nitrogen-to-phosphate ratio
  • RNA

MRSEC Support

  • Shared

PubMed: MeSH publication types

  • Journal Article


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