Biomedical Engineering Reference
In-Depth Information
8 Biodegradable Stimuli-Responsive Systems
8.1 Biodegradable Temperature Responsive Systems
Stimuli-responsive polymers, especially temperature-responsive polymers, have
attracted a great deal of attention in the last two decades as biomedical materials
for drug delivery, separation of bioactive molecules, and tissue engineering
[
294
,
295
]. PNIPAAm is one of the most typical temperature-responsive polymers.
PNIPAAm exhibits a rapid and reversible hydration-dehydration in response to
small changes in the solution temperature around its lower critical solution
temperature (LCST) of 32
C[
296
]. PNIPAAm has been studied for development
of smart materials such as stimuli-responsive particles, surfaces, and hydrogels
[
297
-
300
]. However, PNIPAAm and its copolymers are nonbiodegradable,
presenting an obstacle to their application as implantable biomaterials. Hence,
several types of temperature-responsive biodegradable polymers have been
recently developed [
40
,
301
-
304
].
Some amino acid-based polymers possess unique properties and functions based
on the polar side chains and amide bonds, which can form hydrogen bonds.
Tachibana and coworkers have synthesized poly(amino acid)-based temperature-
responsive polymers, poly(
N
-substituted
a
/
b
-asparagine), through coupling reac-
tion of poly(succinimide) with a mixture of 5-aminopentanol and 6-aminohexanol
[
301
]. The polymer showed LCST-type temperature responsiveness, and the LCST
could be tuned in the range from 23 to 44
C by varying the mixing ratio of
5-aminopentanol and 6-aminohexanol in the coupling reaction. Shimokuri and
coworkers have also synthesized poly(
g
-glutamic acid) derivatives having propyl
amide groups as side chains, i.e., poly(
a
-propyl
g
-glutamate) [
302
]. The polymer
also showed LCST-type phase transition, and the LCST of the polymer was at
around 30
C. Moreover, chemical crosslinking of poly(
a
-propyl
g
-glutamate) with
hexamethylene diisocyanate (HMDI) produced biodegradable hydrogels having a
temperature-responsive shrinking property [
303
].
As described above, we have synthesized PDP, alternating copolymers of an
a
-aspartic acid and a glycolic acid [poly(Glc-Asp)], having pendant carboxylic
groups [
100
]. Generally, the temperature-dependent soluble-insoluble transition
property of a polymer depends strongly on the hydrophobic/hydrophilic balance of
the polymer. We have synthesized poly(Glc-Asp) substituted with moderately
hydrophobic groups (isopropyl amide groups like NIPAAm). The resulting
poly[Glc-Asn(
N
-isopropyl)] showed LCST-type temperature-responsive phase
transition in water at 29
C, as shown in Fig.
20
[
304
]. Degradation of poly
[Glc-Asn(
N
-isopropyl)] to the monomer level occurred via cleavage of the ester
bonds in the main chain, and the resulting degradation products were found to be
nontoxic for cultured cells. Poly[Glc-Asn(
N
-isopropyl)] and related polymers
exhibiting LCST between room temperature and body temperature, no toxicity,
hydrolytic degradation, and chemical reactivity are expected to be applied in
biomedical field.
