Biomedical Engineering Reference
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It was observed that by varying the molar feed ratio of the fatty
amines and the polyamine content, the degree of HA modification
could be controlled in the range of 5-20%. Some of the different
classes of functional HA blocks that were synthesised included
HA derivatised with monofunctional fatty amines (namely,
n-butylamine, C
4
; n-hexylamine, C
6
; n-octylamine, C
8
; dodecylamine,
C
12
; and stearylamine, C
18
), bifunctional fatty amines (namely,
1,6-diaminohexane, C
6
N
2
, 1,8-diaminohexane, C
8
N
2
), and multiple
nitrogen-containing derivatives and polyamines such as pipirazine,
spermine, choline, poly-L-lysine (PLL) and PEI. It was also noticed
that the derivatives with very short alkyl chain lengths such as
butylamine-modified HA with a lipid content of approximately 10-
12% or lower did not promote self-assembly, whereas HA derivatives
modified with fatty amines comprising alkyl chains with six or more
carbon atoms (with approximately 10-15% lipid modification) could
self-assemble to form nanosized particles in deionised water or 1X
phosphate-buffered saline (PBS, pH 7.4). Our data suggested that
a certain amount of lipid modification/hydrophobicity is essential
for the formation of self-assembly with the tested MW of HA [19].
Additionally, several other groups have also been working on
similar strategies. Shen and co-workers [20] successfully conjugated
hydrophobic fatty amines with different chain lengths such as
1-octanamine (OA), 1-laurylamine (LA), 1-octadecylamine (DA) and
spermine (SP) to HA of different molecular weights (9.6, 23 and 45 kDa)
and demonstrated that these conjugates (HA-LA-SP, HA-OA-SP
or HA-DA-SP) could self-assemble into micelles and the sizes of
these particles were dependent on the chain length and the types of
hydrophobic groups present in the fatty acid chain. SP was used as
a cationic side chain for every derivative to neutralise the negative
charge of nucleic acid by electrostatic interactions and entrap that
into the core of HA polymeric micelles. The degree of substitution
(DS) of hydrophobic segments such as OA, LA, DA was determined
by
1
H-nuclear magnetic resonance (NMR). The authors found that,
when the length of the alkyl chains remains unchanged, the DS of
the products seemed to decline as the MW of the HA increased.
They suggested that this could be because the larger MW of the HA
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