Physico-chemical and physiological determinants of lipo-nanoparticle stability

Henry J. Pownall, Jing Liu, Baiba K. Gillard, Dedipya Yelamanchili, Corina Rosales

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Liposome-based nanoparticles (NPs) comprised mostly of phospholipids (PLs) have been developed to deliver diagnostic and therapeutic agents. Whereas reassembled plasma lipoproteins have been tested as NP carriers of hydrophobic molecules, they are unstable because the components can spontaneously transfer to other PL surfaces—cell membranes and lipoproteins—and can be degraded by plasma lipases. Here we review two strategies for NP stabilization. One is to use PLs that contain long acyl-chains: according to a quantitative thermodynamic model and in vivo tests, increasing the chain length of a PL reduces the spontaneous transfer rate and increases plasma lifetime. A second strategy is to substitute ether for ester bonds which makes the PLs lipase resistant. We conclude with recommendations of simple ex vivo and in vitro tests of NP stability that should be conducted before in vivo tests are begun.

Original languageEnglish (US)
Article number102361
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Early online dateFeb 1 2021
StatePublished - Apr 2021


  • Hydrophobic effect
  • Kinetics
  • Lipid transfer
  • Liposomes
  • Nanoparticle stability
  • Thermodynamics

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science


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