Environmental Engineering Reference
In-Depth Information
Fig. 16.3 Synthesis of trimethyl chitosan [
70
]
distilled water for 3 days, and lyophilized further. The same process can be repeated
with lauric acid, myristic acid, palmitic acid, and stearic acid, respectively, to
obtain desired product.
The solubilization of poor water-soluble drugs using
N
-acyl,
O
-acyl-
N
-trimethyl
chitosan chloride (ATMC) micelles as a carrier system was investigated. Long-
chain saturated fatty acids (C
14
) were grafted. The ATMC micelles self-assemble
and were used to encapsulate the poorly soluble drug, Cyclosporine A. These
assemblies were prepared by a dialysis, wherein the drug loading capacity of the
ATMC micelles ranged from 9.6 to 17.1 % and encapsulation capacity ranged from
35.8 to 69.8 %, with the mean micellar particle size of 288 nm. These ATMC
micelles are being investigated as carriers to improve oral administration absorption
of poorly permeable drugs [
72
].
ChitoPEG graft copolymer can be synthesized as reported previously
[
73
]. Briefly, 100 mg of chitosan is dissolved in 0.2 ml of deionized water and
diluted with 9.8 ml of DMSO. To this solution, calculated amount of methoxy poly
(ethylene glycol) (MPEG)-
N
-hydroxysuccimide (NHS) dissolved in 2 ml of DMSO
is added and reacted for overnight at nitrogen atmosphere. After that, the resulting
solution is dialyzed using dialysis tube against a plenty of deionized water for
2 days followed by its lyophilization. Generally, chitosan is not soluble in
dichloromethane (DCM) while MPEG is freely soluble in it. Therefore, unreacted
MPEG-NHS is removed by suspending lyophilized solid into a plenty of DCM for
three times. After that, ChitoPEG copolymer is fractionated into deionized water
followed by its lyophilization. The methotrexate (MTX)-incorporated polymeric
micelles of ChitoPEG copolymer has a particle size of around 50-100 nm. The drug
contents of the polymeric micelle are around 4-12 % and the loading efficiency of
MTX in the polymeric micelles is higher than 60 % (w/w) for all of the formulations
(Fig.
16.4
).
Stearic acid (SA) grafted chitosan oligosaccharide (CSOS-SA) can be synthe-
sized by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated cou-
pling reaction. Low molecular weight chitosan (20 kDa molecular wt)-stearic
acid (SA) is obtained via the reaction of carboxyl groups of SA with amino groups
of CSOS in the presence of EDC, according to the previous reports [
74
,
75
]. Briefly,