Biomedical Engineering Reference
In-Depth Information
5 )
Viscoseparation:
HyA is used to inhibit adhesion between two surgically
traumatized tissue surfaces.
The problem with HyA containing products for the application described before
is the short half-life time of the polymer, which leads to numerous repetitions of
the medical treatment. Therefore, several attempts have been made to crosslink
the HyA single strands to create hydrogels with very high molecular masses. This
delays the degradation of the polymer.
The group from Š olt é s
et al.
synthesized hydrogels for nonsurgical, viscosup-
plementatious applications [151]. Their patented system is the injection of a cock-
tail of two HyA derivates, namely,
n
- acetylurea - HyA and
- cyclodextrin - HyA,
which spontaneously associate to hydrogels. To ensure that the hydrogel is not
formed before the injection, a drug molecule is added which blocks the association
process until it is degraded in the body. A new synthetic route to these HyA deri-
vates was proposed by Charlot
et al.
[152]. Other hydrogels for viscoaugmentation
applications were described by Shu
et al.
, who synthesized thiolated HyA deriva-
tives and formed hydrogels through disulfi de crosslinking or by coupling to
β
-
unsaturated esters and amides of polyethylene crosslinkers [153] . The polymerization
time could be adjusted from 10 min up to several days, depending on the chemical
structure of the crosslinker.
Pulpitt
et al.
and Jia
et al.
used another crosslinking strategy based on hydrazide-
and aldehyde - modifi ed HyA [154, 155]. The hydrazide is generated through cou-
pling of adipic dihydrazide to the carboxylic groups of HyA. The aldehyde-modifi ed
HyA can be obtained by oxidation of the diol moiety with sodium periodate. These
two functional groups react spontaneously to hydrogels via hydrazone formation.
Another hydrogel formation mechanism is described by Kurisawa
et al.
who syn-
thesized an injectable HyA-tyramine conjugates which polymerized via enzyme-
induced oxidative coupling [156].
HyA can be used as drug carrier to improve the solubility of pharmaceuticals
or to decrease their toxicity. A review from Bettolo
et al.
describes different HyA-
paclitaxel bioconjugates, which overcome the initial mentioned problems [157].
Paclitaxel is a well-known antitumor agent used for the treatment of breast and
ovarian cancer. A controlled release in the tumor region can be assumed due to
the overexpression of the HyA CD 44 receptor in various cancer cell lines.
Approaches toward HyA as carrier substrate for carboranes in boron neutron
capture therapy have been made by Di Meo
et al.
[158]. This therapy includes the
delivery of
10
B to the tumor tissue and irradiation thereof with small doses of
thermal/epithermal neutrons. This leads to ablation of the malignant cells.
There are numerous applications and chemical modifi cation strategies to use
HyA in the fi eld of drug delivery: (i) Motokawa
et al.
developed a strategy of sus-
tained release of erythropoietin through noncovalent encapsulation in HyA hydro-
gels for anemia treatment synthesized with the aldehyde/hydrazine method [159].
(ii) Kinetics of the drug release of esterifi ed HyA-steroid conjugates for the treat-
ment of infl ammatory joint diseases was studied with NMR [160]. (iii) HyA and
polyglutamate block polymers were synthesized using “ click chemistry ” [161] .
α
,
β
