Dynamic and structural aspects of PEGylated liposomes monitored by NMR

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Cecilia Leal
  • Sibylla Rognvaldsson
  • Sigrid Fossheim
  • Esben A. Nilssen
  • Daniel Topgaard
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Fysikalisk kemi

Nyckelord

Originalspråkengelska
Sidor (från-till)485-493
TidskriftJournal of Colloid and Interface Science
Volym325
Utgåva nummer2
StatusPublished - 2008
PublikationskategoriForskning
Peer review utfördJa