Article ID Journal Published Year Pages File Type
2485412 Journal of Pharmaceutical Sciences 2012 15 Pages PDF
Abstract
The effects of acyl chain length and unsaturation on physicochemical characteristics and transfection efficiency of novel nanomicelles of N-acyl-substituted low-molecular-weight chitosan (N-acyl LMWC) were studied. After transfection optimization, 18-carbon chain length grafts were selected, and N-acyl LMWCs were prepared with increasing unsaturation (18:1-18:3 carbon acyl grafts). N-acyl LMWCs were characterized using infrared spectroscopy and elemental analysis. The effect of DNA addition on size and zeta potential of N-acyl LMWCs was determined by dynamic light scattering. N-acyl LMWC-plasmid DNA (pDNA) polyplex stability was confirmed using gel electrophoresis. Transfection efficiency of the derivative polymers was visualized in human embryonic kidney cells using a plasmid encoding green fluorescent protein by confocal fluorescence microscopy and was quantified using therapeutic plasmids encoding for interleukin-4 and interleukin-10. N-acyl LMWCs could form cationic nanomicelles with average hydrodynamic size between 73 and 132 nm. DNA addition to nanomicelles led to minimal increase in the size. N-acyl LMWC-pDNA polyplexes showed excellent stability on storage and could protect DNA from enzymatic degradation. The transfection efficiencies of N-acyl LMWCs with 18:1 and 18:2 grafts were comparable with FuGENE® HD but were approximately eightfold and 35-fold greater as compared with LMWC and naked DNA, respectively. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.
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