Biomedical Engineering Reference
In-Depth Information
a phase transition to release the drug molecules [53, 54]. One such thermosensitive
polymer is poly(
N
- isopropylacrylamide) ( poly(NIPAAm) ), which undergoes a coil -
globule phase transition in water at its lower critical solution temperature (LCST)
of
32 °C, changing from a hydrophilic state below the LCST to a hydrophobic
state above it [55]. The LCST of the polyNIPAAm can be tuned to above normal
body temperature by incorporating comonomer units, such as
N,N
- dimethylacryl-
amide [56]. A major disadvantage of poly(NIPAAm) and its copolymer with
N,N
-
dimethylacrylamide, however, is its lack of biodegradability. In order to improve
the biodegradability, a water - soluble dextran -
g
- poly(
N
- isopropylacrylamide -
co
-
N,N
-
dimethylacrylamide) [ dextran -
g
- poly(NIPAAm -
co
- DMAAm) ] polymer was synthe-
sized via a four-step process:
•
Synthesis of the poly(NIPAAm -
co
-DMAAm) with a methyl ester end group.
•
Transformation of the − COOCH
3
end group into − NHNH
2
.
•
Reaction of dextran with 4 - nitrophenyl chloroformate.
•
Synthesis of the dextran -
g
- poly(NIPAAm -
co
- DMAAm) by coupling the
4-nitrophenyl chloroformate-activated dextran to the NH
2
groups of
poly(NIPAAm-
co
- DMAAm) [53, 56] .
∼
38 ° C. The Fe
3
O
4
nanoparticles were prepared
using a high-temperature decomposition method and were modifi ed with bifunc-
tional methyl- 3 - mercaptopropionate (HSCH
2
CH
2
COOCH
3
), which was chemically
bonded to the surface of the magnetite nanoparticles via Fe-S covalent bonds. The
This polymer exhibited a LCST of
∼
−
NHNH
2
functional group by a hydra-
zinolysis reaction to facilitate the subsequent conjugation of the anticancer drug,
DOX [53]. The hydrazone linkages formed between DOX and the
OCH
3
group was then converted to the
−
NHNH
2
end
groups are acid-labile, and hence the conjugated drug may be released in the low-
acid environment (pH 5-5.5) present in the endosome of cancer cells. The encap-
sulation of the DOX-conjugated MNPs by the dextran-
g
- poly(NIPAAm -
co
- DMAAm)
polymer was carried out by sonicating the DOX- conjugated MNPs, dextran -
g
-
poly(NIPAAm -
co
-DMAAm) polymer and 1,6-diaminohexane (in the weight ratio
of 2 : 3 : 1) in dimethylsulfoxide ( DMSO ) for 2 h at 40 - 50 ° C. Since the dextran -
g
-
poly(NIPAAm -
co
- DMAAm) polymer contains active 4 - nitrophenyl chloroformate
groups, it can be crosslinked by 1,6-diaminohexane, thus encapsulating the mag-
netic nanoparticles. The weight percentage of drug present in the carrier was
−
9%.
Based on the results of TGA, it was deduced that the drug carrier comprised
60 wt% of Fe
3
O
4
nanoparticles and 40 wt% of organic substances, inclusive of the
drug and the polymer. After encapsulation by the polymer, the size of the nanopar-
ticles increased from
∼
8 nm. At 20 °C, the drug release was lower as compared
to that at 37 or 40 °C, where the release was rapid for the initial 5 h and followed
by a sustained release at longer duration, with higher releases in a mildly acidic
buffer solution (pH 5.3). The drug release was envisaged to occur by the collapse
of the encapsulated thermoresponsive polymer and cleavage of the acid- labile
hydrazone linkage.
∼
5 to
∼
