Catalytic Synthesis and Characterization of Biodegradable ...
Catalytic Synthesis and Characterization of Biodegradable ...
Catalytic Synthesis and Characterization of Biodegradable ...
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initialization <strong>of</strong> the device by applying an inverse voltage.<br />
1.6.2 Radical Polymers for Biomedical Applications<br />
1.6.2.1 Nitric Oxide Release Systems<br />
- 45 -<br />
Polymerization <strong>and</strong> Applications <strong>of</strong> <strong>Biodegradable</strong> Polyesters<br />
Nitric oxide (NO•) is a small but highly reactive free radical with exp<strong>and</strong>ing known<br />
biological activities. Its essential roles involve the regulatory agent for normal physiological<br />
activities <strong>and</strong> cytotoxic species in diseases <strong>and</strong> their treatments. There have been numerous<br />
examples <strong>of</strong> application <strong>of</strong> the nitric oxide on disease treatments, such as antiviral compounds,<br />
cancer treatment, anti-inflammatory drugs <strong>and</strong> other nitric oxide-related diseases treatment.<br />
However, the excess introduction <strong>of</strong> nitric oxide into body may induce significant adverse<br />
side effects like microvascular leakage, tissue damage in cystic fibrosis, septic shock, B-cell<br />
destruction, <strong>and</strong> possible mutagenic risk. 193 Therefore, it is very important to develop smart<br />
delivery vehicles for control release <strong>of</strong> the nitric oxide.<br />
<strong>Biodegradable</strong> polymers are known to be biocompatible <strong>and</strong> degradable in physiological<br />
conditions which have been widely utilized as drug delivery vehicles in the forms <strong>of</strong> matrices<br />
or nanoparticles. Accordingly, pioneered works by C. C. Chu <strong>and</strong> co-workers have reported to<br />
incorporate <strong>of</strong> stable nitric oxide radicals to either the chain end or backbone <strong>of</strong> the<br />
biodegradable polymers. 193-196 In such contributions, nitric oxide derivative, tampamine<br />
nitroxyl radical (4-amino-2,2,6,6-tetramethylpiperidine-1-oxy, TAM) have been chemically<br />
coupled with various biodegradable polymers such as polyglycolide (PGA), poly(acrylic<br />
acid/lactide/ε-caprolactone) (PBLCA) <strong>and</strong> poly(ester amide)s (PEAs). The biological<br />
activities <strong>of</strong> these TAM-incorporated polymers <strong>and</strong> the release kinetic <strong>of</strong> the TAM from the<br />
polymer matrices have also been evaluated. For example, the level <strong>of</strong> the retardation <strong>of</strong><br />
smooth muscle cell (SMC) <strong>of</strong> the TAM-PGA was conducted in vitro cell culture (Figure<br />
1.6.6). The TAM-PGA was found to show pr<strong>of</strong>ound retardation <strong>of</strong> the proliferation <strong>of</strong> SMC as<br />
similar with the TAM free nitroxyl radicals at concentration <strong>of</strong> 1 μg/mL. Thus, it appeared<br />
that the long PGA segments had no evidently interference on the biological functions <strong>of</strong><br />
nitroxyl radicals incorporated. However, the incorporation <strong>of</strong> TAM into the polymer chain<br />
end have limitation in the TAM content in the polymer, improved strategies have also been<br />
proposed by the authors via conjugating the TAM to the backbone <strong>of</strong> the biodegradable<br />
polymers such as PBLCA <strong>and</strong> PEAs. 193, 194 Up to 8.32% (wt %) <strong>of</strong> the TAM content in