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Formation of highly structured cubic micellar lipid nanoparticles of soy phosphatidylcholine and glycerol dioleate and their degradation by triacylglycerol lipase

Wadsäter, Maria LU ; Barauskas, Justas; Nylander, Tommy LU and Tiberg, Fredrik LU (2014) In ACS Applied Materials and Interfaces 6(10). p.7063-7069
Abstract
Lipid nanoparticles of reversed internal phase structures, such as cubic micellar (I2) structure show good drug loading ability of peptides and proteins as well as some small molecules. Due to their controllable small size and inner morphology, such nanoparticles are suitable for drug delivery using several different administration routes, including intravenous, intramuscular and subcutaneous injection. A very interesting system in this regard, is the two component soy phosphatidylcholine (SPC)/glycerol dioleate (GDO) system, which depending on the ratio of the lipid components form a range of reversed liquid crystalline phases. For a 50/50 (wt/wt) ratio in excess water, these lipids have been shown to form a reversed cubic micellar (I2)... (More)
Lipid nanoparticles of reversed internal phase structures, such as cubic micellar (I2) structure show good drug loading ability of peptides and proteins as well as some small molecules. Due to their controllable small size and inner morphology, such nanoparticles are suitable for drug delivery using several different administration routes, including intravenous, intramuscular and subcutaneous injection. A very interesting system in this regard, is the two component soy phosphatidylcholine (SPC)/glycerol dioleate (GDO) system, which depending on the ratio of the lipid components form a range of reversed liquid crystalline phases. For a 50/50 (wt/wt) ratio in excess water, these lipids have been shown to form a reversed cubic micellar (I2) phase of the Fd3m structure. Here we demonstrate that this SPC/GDO phase, in the presence of small quantities (5-10 wt%) of Polysorbate 80 (P80), can be dispersed into nanoparticles, still with well-defined Fd3m structure. The resulting nanoparticle dispersion has a narrow size distribution and exhibit good long-term stability. In pharmaceutical applications, biodegradation pathways of the drug delivery vehicles and their components are important considerations. In the second part of the study we show how the structure of the particles evolves during exposure to a triacylglycerol lipase (TGL) under physiological-like temperature and pH. TGL catalyses the lipolytic degradation of acylglycerides, such as GDO, to monoglycerides, glycerol and free fatty acids. During the degradation, the interior phase of the particles is shown to undergo continuous phase transitions from the reversed I2 structure to structures of less negative curvature (2D hexagonal, bicontinuous cubic and sponge), ultimately resulting in the formation of multi-lamellar vesicles. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ACS Applied Materials and Interfaces
volume
6
issue
10
pages
7063 - 7069
publisher
The American Chemical Society
external identifiers
  • pmid:24779728
  • wos:000336639200012
  • scopus:84901649928
ISSN
1944-8244
DOI
10.1021/am501489e
language
English
LU publication?
yes
id
50914abc-1fe7-4553-9299-c6480021ff27 (old id 4436066)
date added to LUP
2014-05-07 17:47:07
date last changed
2017-09-10 03:20:50
@article{50914abc-1fe7-4553-9299-c6480021ff27,
  abstract     = {Lipid nanoparticles of reversed internal phase structures, such as cubic micellar (I2) structure show good drug loading ability of peptides and proteins as well as some small molecules. Due to their controllable small size and inner morphology, such nanoparticles are suitable for drug delivery using several different administration routes, including intravenous, intramuscular and subcutaneous injection. A very interesting system in this regard, is the two component soy phosphatidylcholine (SPC)/glycerol dioleate (GDO) system, which depending on the ratio of the lipid components form a range of reversed liquid crystalline phases. For a 50/50 (wt/wt) ratio in excess water, these lipids have been shown to form a reversed cubic micellar (I2) phase of the Fd3m structure. Here we demonstrate that this SPC/GDO phase, in the presence of small quantities (5-10 wt%) of Polysorbate 80 (P80), can be dispersed into nanoparticles, still with well-defined Fd3m structure. The resulting nanoparticle dispersion has a narrow size distribution and exhibit good long-term stability. In pharmaceutical applications, biodegradation pathways of the drug delivery vehicles and their components are important considerations. In the second part of the study we show how the structure of the particles evolves during exposure to a triacylglycerol lipase (TGL) under physiological-like temperature and pH. TGL catalyses the lipolytic degradation of acylglycerides, such as GDO, to monoglycerides, glycerol and free fatty acids. During the degradation, the interior phase of the particles is shown to undergo continuous phase transitions from the reversed I2 structure to structures of less negative curvature (2D hexagonal, bicontinuous cubic and sponge), ultimately resulting in the formation of multi-lamellar vesicles.},
  author       = {Wadsäter, Maria and Barauskas, Justas and Nylander, Tommy and Tiberg, Fredrik},
  issn         = {1944-8244},
  language     = {eng},
  number       = {10},
  pages        = {7063--7069},
  publisher    = {The American Chemical Society},
  series       = {ACS Applied Materials and Interfaces},
  title        = {Formation of highly structured cubic micellar lipid nanoparticles of soy phosphatidylcholine and glycerol dioleate and their degradation by triacylglycerol lipase},
  url          = {http://dx.doi.org/10.1021/am501489e},
  volume       = {6},
  year         = {2014},
}