TY - JOUR
T1 - Disc-shaped polyoxyethylene glycol glycerides gel nanoparticles as novel protein delivery vehicles
AU - Codoni, Doroty
AU - Cowan, Jonathan
AU - Bradley, Jenna
AU - McAuley, William J
AU - O'Connell, Maria A
AU - Qi, Sheng
N1 - This is the Accepted Manuscript version of the following article: D. Codoni, et al., “Disc-shaped polyoxyethylene glycol glycerides gel nanoparticles as novel protein delivery vehicles”, International Journal of Pharmaceutics, Vol. 496(2), November 2015.
The final published version is available online at: https://doi.org/10.1016/j.ijpharm.2015.10.067
PY - 2015/12/30
Y1 - 2015/12/30
N2 - Disc-shaped nanoparticles with high aspect ratios have been reported to show preferential cellular uptake in vitro by mammalian cells. However, engineering and producing such disc-shaped nanoparticles are often complex. This study reports for the first time the use of a single, approved pharmaceutical excipient to prepare stable disc-shaped nanoparticles with a high aspect ratio via a simple, organic solvent free process. These disc-shaped nanoparticles were formed by fragmentation of stearoyl macrogol-32 glycerides (Gelucire 50/13) hydrogels. The nanoparticles showed good physical stability as a result of their outer coating of polyethylene glycol (PEG) that is a part of Gelucire composition. Using lysozyme as a model hydrophilic protein, these nanoparticles demonstrated a good loading capacity for hydrophilic macromolecules, mainly via surface adsorption. As a result of the higher hydrophobicity of the core of the nano-discs, the loading efficiency of hydrophobic model components, such as Coumarin-6, was significantly increased in comparison to the model hydrophilic compound. These Gelucire nano-discs exhibited no cytotoxicity at the tested level of 600μg/ml for Caco-2 cells. Rapid in vitro cellular uptake of the disc-shaped nanoparticles by Caco-2 cells was observed. This rapid internalisation was attributed to the high aspect ratio of the disc-shape nanoparticles which provides a high contact surface area between the particles and cells and may lower the strain energy required for membrane deformation during uptake. The results of this study demonstrate the promising potential of Gelucire nano-discs as effective nanocarriers for drug delivery and which can be manufactured using a simple solvent-free process.
AB - Disc-shaped nanoparticles with high aspect ratios have been reported to show preferential cellular uptake in vitro by mammalian cells. However, engineering and producing such disc-shaped nanoparticles are often complex. This study reports for the first time the use of a single, approved pharmaceutical excipient to prepare stable disc-shaped nanoparticles with a high aspect ratio via a simple, organic solvent free process. These disc-shaped nanoparticles were formed by fragmentation of stearoyl macrogol-32 glycerides (Gelucire 50/13) hydrogels. The nanoparticles showed good physical stability as a result of their outer coating of polyethylene glycol (PEG) that is a part of Gelucire composition. Using lysozyme as a model hydrophilic protein, these nanoparticles demonstrated a good loading capacity for hydrophilic macromolecules, mainly via surface adsorption. As a result of the higher hydrophobicity of the core of the nano-discs, the loading efficiency of hydrophobic model components, such as Coumarin-6, was significantly increased in comparison to the model hydrophilic compound. These Gelucire nano-discs exhibited no cytotoxicity at the tested level of 600μg/ml for Caco-2 cells. Rapid in vitro cellular uptake of the disc-shaped nanoparticles by Caco-2 cells was observed. This rapid internalisation was attributed to the high aspect ratio of the disc-shape nanoparticles which provides a high contact surface area between the particles and cells and may lower the strain energy required for membrane deformation during uptake. The results of this study demonstrate the promising potential of Gelucire nano-discs as effective nanocarriers for drug delivery and which can be manufactured using a simple solvent-free process.
UR - http://www.sciencedirect.com/science/article/pii/S0378517315303355
U2 - 10.1016/j.ijpharm.2015.10.067
DO - 10.1016/j.ijpharm.2015.10.067
M3 - Article
C2 - 26536528
SN - 0378-5173
VL - 496
SP - 1015
EP - 1025
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 2
ER -