Optimizing Drug Delivery: Characterization of DLin-KC2-DMA/Distearoylphosphatidylserine by 31P and 2H NMR Spectroscopy

Author: 
Date created: 
2013-12-10
Identifier: 
etd8186
Keywords: 
Lipid nanoparticles
Drug delivery
Inverted hexagonal (HII)
Phase transition
2H NMR spectroscopy
Abstract: 

Lipid nanoparticles (LNPs) are used to deliver siRNA to hepatocytes via endocytosis and subsequent endosomal release. With 99% of the LNPs taken up by the cell via endocytosis, only 1% of the siRNA is actually released into the cell cytosol. To improve the effectiveness of LNPs association with and disruption of endosomal membranes, the biophysical properties of a model system composed of 1:1 molar ratio of anionic lipid 1,2-distearoyl(d70)-sn-glycero-3-[phospho-L-serine] (DSPS-d70) and the cationic lipid DLin-KC2-DMA are characterized by 2H and 31P NMR spectroscopy. The bilayer to inverted hexagonal (HII) phase transition of the model system was shown to be influenced by temperature, pH and salt concentration. The order parameter profiles are obtained, revealing the extent of acyl chain movement of DSPS-d70 in bilayer and HII phases. The results help provide insights into computational simulation and eventually optimized LNPs design.

Document type: 
Thesis
Rights: 
Copyright remains with the author. The author granted permission for the file to be printed, but not for the text to be copied and pasted.
File(s): 
Supervisor(s): 
Jenifer Thewalt
Department: 
Science: Department of Molecular Biology and Biochemistry
Thesis type: 
(Thesis) M.Sc.
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