Formation of Highly Structured Cubic Micellar Lipid Nanoparticles of Soy Phosphatidylcholine and Glycerol Dioleate and Their Degradation by Triacylglycerol Lipase

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Formation of Highly Structured Cubic Micellar Lipid Nanoparticles of Soy Phosphatidylcholine and Glycerol Dioleate and Their Degradation by Triacylglycerol Lipase

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Publication Article, peer reviewed scientific
Title Formation of Highly Structured Cubic Micellar Lipid Nanoparticles of Soy Phosphatidylcholine and Glycerol Dioleate and Their Degradation by Triacylglycerol Lipase
Author(s) Wadsater, Maria ; Barauskas, Justas ; Nylander, Tommy ; Tiberg, Fredrik
Date 2014
English abstract
Lipid nanoparticles of reversed internal phase structures, such as cubic micellar (I-2) 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 (w/w) ratio in excess water, these lipids have been shown to form a reversed cubic micellar (I-2) 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 catalyzes 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 12 structure to structures of less negative curvature (2D hexagonal, bicontinuous cubic, and sponge), ultimately resulting in the formation of multilamellar vesicles.
DOI http://dx.doi.org/10.1021/am501489e (link to publisher's fulltext)
Publisher American Chemical Society
Host/Issue ACS Applied Materials and Interfaces;10
Volume 6
ISSN 1944-8244
Pages 7063-7069
Language eng (iso)
Subject(s) cubic micellar nanoparticles
lipids
liquid crystals
intravenous
parenteral
drug delivery
triacylglycerol lipase and phase transitions
Sciences
Research Subject Categories::NATURAL SCIENCES
Handle http://hdl.handle.net/2043/18273 (link to this page)

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