Dynamic and structural aspects of PEGylated liposomes monitored by NMR

Cecília Leal, Sibylla Rögnvaldsson, Sigrid Fossheim, Esben A. Nilssen, Daniel Topgaard

Research output: Contribution to journalArticlepeer-review


Proton-detected NMR diffusion and 31P NMR chemical shifts/bandwidths measurements were used to investigate a series of liposomal formulations where size and PEGylation extent need to be controlled for ultrasound mediated drug release. The width of the 31P line is sensitive to aggregate size and shape and self-diffusion 1H NMR conveys information about diffusional motion, size, and PEGylation extent. Measurements were performed on the formulations at their original pH, osmolality, and lipid concentration. These contained variable amounts of PEGylated phospholipid (herein referred to as PEG-lipid) and cholesterol. At high levels of PEG-lipid (11.5 and 15 mol%) the self-diffusion 1H NMR revealed the coexistence of two entities with distinct diffusion coefficients: micelles (1.3 to 3 × 10-11   m2 / s) and liposomes (≈ 5 × 10-12   m2 / s). The 31P spectra showed a broad liposome signal and two distinct narrow lines that were unaffected by temperature. The narrow lines arise from mixed micelles comprising both PEG-lipids and phospholipids. The echo decay in the diffusion experiments could be described as a sum of exponentials revealing that the exchange of PEG-lipid between liposomes and micellar aggregates is slower than the experimental observation time. For low amounts of PEG-lipid (1 and 4.5 mol%) the 31P spectra consisted of a broad signal typically obtained for liposomes and the diffusion data were best described by a single exponential decay attributed solely to liposomes. For intermediate amounts of PEG-lipid (8 mol%), micellization started to occur and the diffusion data could no longer be fitted to a single or bi-exponential decay. Instead, the data were best described by a log-normal distribution of diffusion coefficients. The most efficient PEG-lipid incorporation in liposomes (about 8 mol%) was achieved for lower molecular weight PEG (2000 Da vs 5000 Da) and when the PEG-lipid acyl chain length matched the acyl chain length of the liposomal core phospholipid. Simultaneously to the PEGylation extent, self-diffusion 1H NMR provides information about the size of micelles and liposomes. The size of the micellar aggregates decreased as the PEG-lipid content was increased while the liposome size remained invariant.

Original languageEnglish (US)
Pages (from-to)485-493
Number of pages9
JournalJournal of Colloid And Interface Science
Issue number2
StatePublished - Sep 15 2008
Externally publishedYes


  • P NMR
  • Drug delivery
  • PEG-lipid micelles
  • PEGylated liposomes
  • Self-diffusion H NMR
  • Ultrasound

ASJC Scopus subject areas

  • Colloid and Surface Chemistry
  • Physical and Theoretical Chemistry
  • Surfaces and Interfaces


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