Chemical Modifications of Hyaluronan for Therapeutic Applications - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 155

[30]. All these strategies have their own limitations as they employ
harsh reaction conditions, causing reduction in polymer chain length
by at least one order of magnitude [20].
8.3.3 Esterification
8.3.3.1 Acrylation of Hyaluronic Acid
Normal acrylation of HA is performed in dimethyl sulfoxide by
mixing HA (tetrabutylammonium (TBA)) salt, (benzotriazol-1-yloxy)
tris (dimethylamino)phosphonium hexafluorophosphate, AEMA and
N , N -diisopropylethylamine [31]. An alternative method involves
acrylation of HA using a large excess of glycidyl methacrylate. [32].
Methacrylation of HA is also performed in water at pH 6.5 by using
two mole equivalent EDC and N -(3-aminopropyl) methacrylamide
with respect to the disaccharide unit [33] or using glycidyl
methacrylate with tetrabutylammonium bromide as the catalyst.
8.3.3.2 Alkylation of Hyaluronic Acid
Alkylation can be used to prepare amphiphilic HA derivatives.
Alkylation of HA carboxylic groups can be performed using HA-
TBA salt and alkyl halides, such as alkyl iodides or bromides, in an
organic solvent [34, 35]. Alkylation of HA is also performed in an
aqueous environment by using adipic dihydrazide modified HA and
1-decanal [36].
8.3.3.3 Huisgen Cycloaddition (Click Chemistry)
The Huisgen cycloaddition reaction of azides with alkynes to produce
triazoles was used to produce HA hydrogels and to encapsulate yeast
cells during crosslinking. In this method, azide and alkyne functional
groups were installed on HA using EDC chemistry. The hydrogel