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Dynamic and structural aspects of PEGylated liposomes monitored by NMR

Leal, Cecilia; Rognvaldsson, Sibylla; Fossheim, Sigrid; Nilssen, Esben A. and Topgaard, Daniel LU (2008) In Journal of Colloid and Interface Science 325(2). p.485-493
Abstract
Proton-detected NMR diffusion and P-31 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 P-31 line is sensitive to aggregate size and shape and self-diffusion H-1 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 1 H NMR revealed the coexistence of two entities with... (More)
Proton-detected NMR diffusion and P-31 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 P-31 line is sensitive to aggregate size and shape and self-diffusion H-1 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 1 H NMR revealed the coexistence of two entities with distinct diffusion coefficients: micelles (1.3 to 3 x 10(-11) m(2)/S) and liposomes (approximate to 5 x 10(-12) m(2)/s). The P-31 spectra showed a broad liposome signal and two distinct narrow lines that were unaffected by temperature. The narrow lines arise front 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 31 P 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 1 H NMR provides information about the size of micelles and liposomes. The size of the nuicellar aggregates decreased as the PEG-lipid content was increased while the liposome size remained invariant. (C) 2008 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
self-diffusion H-1 NMR, PEGylated liposomes, PEG-lipid micelles, NMR, drug delivery, ultrasound, P-31
in
Journal of Colloid and Interface Science
volume
325
issue
2
pages
485 - 493
publisher
Elsevier
external identifiers
  • wos:000258553900028
  • scopus:48949089840
ISSN
1095-7103
DOI
10.1016/j.jcis.2008.05.051
language
English
LU publication?
yes
id
c68778f0-689f-4fb4-b959-e1afb17d582c (old id 1251891)
date added to LUP
2008-11-18 15:35:18
date last changed
2017-08-13 03:46:21
@article{c68778f0-689f-4fb4-b959-e1afb17d582c,
  abstract     = {Proton-detected NMR diffusion and P-31 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 P-31 line is sensitive to aggregate size and shape and self-diffusion H-1 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 1 H NMR revealed the coexistence of two entities with distinct diffusion coefficients: micelles (1.3 to 3 x 10(-11) m(2)/S) and liposomes (approximate to 5 x 10(-12) m(2)/s). The P-31 spectra showed a broad liposome signal and two distinct narrow lines that were unaffected by temperature. The narrow lines arise front 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 31 P 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 1 H NMR provides information about the size of micelles and liposomes. The size of the nuicellar aggregates decreased as the PEG-lipid content was increased while the liposome size remained invariant. (C) 2008 Elsevier Inc. All rights reserved.},
  author       = {Leal, Cecilia and Rognvaldsson, Sibylla and Fossheim, Sigrid and Nilssen, Esben A. and Topgaard, Daniel},
  issn         = {1095-7103},
  keyword      = {self-diffusion H-1 NMR,PEGylated liposomes,PEG-lipid micelles,NMR,drug delivery,ultrasound,P-31},
  language     = {eng},
  number       = {2},
  pages        = {485--493},
  publisher    = {Elsevier},
  series       = {Journal of Colloid and Interface Science},
  title        = {Dynamic and structural aspects of PEGylated liposomes monitored by NMR},
  url          = {http://dx.doi.org/10.1016/j.jcis.2008.05.051},
  volume       = {325},
  year         = {2008},
}