Chitosan Derivatives - Chitosan Based Hydrogels: Functions and Applications - page 57

chitosan, some of the amino groups are converted to anionic centers and the polymer
attains better polyelectrolyte properties, which can be focused on developing potential
drug carriers in the form of micelles or microcapsules [291,308]. N -Alkyl-O-sulfated chito-
san has amphiphilicity since it carries long-chain alkyl groups having hydrophobic nature
and sulfated groups having hydrophilic nature. This amphiphilic polymer has been shown
to form micelles with physical entrapment of water-insoluble drugs such as taxol in signifi-
cant concentrations [126,139]. The polyelectrolyte character is also revealed to be useful to
form micrometer-sized hollow shells by means of a layer-by-layer technique, and perme-
ation of the macromolecular fluorophore was observed [140]. Apart from these valuable
biological properties, chitosan sulfates exhibit high sorption capacities as expected, and
are of great advantage in metal ion recovery [123].
2.7 Phosphorylated Chitosan
The introduction of phosphonic acid or phosphonate groups onto chitin and chitosan by
reaction of a phosphorylating agent onto the amino groups is known to increase the
chelating properties [141-143] of chitin and chitosan and could modify its solubility.
Several techniques ( cf. Figure 2.16) for obtaining phosphate derivatives of chitin and chi-
tosan have been proposed because of the interesting biological and chemical properties
of such compounds.
The reaction of chitin with phosphorus pentoxide was found to give water-soluble phos-
phorylated chitin of high DS, constituting a strategy to overcome this major drawback of
chitin and its derivatives. Phosphorylated chitin (P-chitin) and chitosan (P-chitosan) were
prepared by heating chitin or chitosan with orthophosphoric acid and urea in DMF [144-
146]. Urea is added to the reaction media to act as a reaction promoter. P-chitin and
P-chitosan were also prepared by the reaction of chitin or chitosan with phosphorus pen-
toxide in MSA [147,148]. The phosphorylation reactions of chitin and chitosan in phospho-
rus pentoxide-methanesulfonic acid were found to be very efficient [149-152]. In this
method, MSA is a good solvent for chitin or chitosan but also acts as an efficient catalyst
for the esterification reaction. However, in this case it was found that only the P-chitosan
with low DS was water soluble. The incorporation of methylene phosphonic groups into
chitosan allowed solubility in water under neutral conditions [153]. A water-soluble
N -methylene phosphonic chitosan (NMPC) was also synthesized using chitosan, phos-
phorous acid, and formaldehyde.
Chitosan- O -ethyl phosphonate can be prepared using KOH/methanol and 2-chloroethyl
phosphonic acid under mild conditions as reported earlier [154]. The preparation of new
types of phosphorylated chitosan using NaOH, n -hexane with diethyl chlorophosphate
(phosphorylating agent) under a heterogeneous system has been reported [155]. The main
difference in this reaction is that the reaction was carried out in n -hexane, an inert solvent,
because the 2-propanol usually employed could be attacked by chlorophosphate, yielding
undesired products. In these systems alkali chitosan is being used to prepare the chitosan
alkyl phosphate/chitosan- O -ethyl phosphonate, in order to increase the reactivity of
hydroxyl groups and to favor the coupling reaction with diethyl chlorophosphate/2-chloro
ethyl phosphonic acid.
The introduction of a hydrophobic alkyl chain into free amino groups of N -methy-
lenephosphonic chitosan by a reductive amine reaction leads to new amphiphilic chitosan