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by Kasab et al. Renal angiograms obtained before and after embolization and also the
histopathological observations showed the feasibility of using these microspheres as
an alternative chemoembolization agent [117]. Epidural analgesic effects of tramadol
released from PHB microspheres were observed for 21 hr, whereas an equal dose of
free tramadol was effective for less than 5 hr. It was suggested that controlled release
of tramadol from PHB microspheres in vivo is possible, and pain relief during epidural
analgesia is prolonged by this drug formulation compared with free tramadol [128].
16.4 CONCLUSION
The observed data indicates that the wide prospects in applications of drug-loaded
medical devices and microspheres on the base of PHB as implantable and injectable
therapeutic systems in medicine for treatment of various diseases: cancer, cardiovas-
cular diseases, tuberculosis, osteomyelitis, arthritis, and so on. Besides application of
PHB for producing of medical devices and systems of sustained drug delivery, PHB
can be used for production of systems for controlled release of activators or inhibitors
of enzymes. The use of these systems allows the development of the physiological
models for prolonged local activation or inhibition of enzymes in vivo . The PHB is
a perspective tool in design of novel physiological models due to minimal adverse
inflammatory tissue reaction to PHB matrices implantation or PHB microspheres ad-
ministration. A system of sustained NO donor delivery on basis of PHB was devel-
oped. This system can be used for study of prolonged NO action on normal tissues of
blood vessels in vivo . The development of in vivo model of prolonged NO local action
on vascular tissues is a difficult problem, because NO donors deliver NO at most only
for a few minutes. We have developed a model of prolonged local NO action on ap-
propriate artery on basis of PHB loaded with a new effective NO donor, FPTO [133]. It
has been shown that FPTO loaded PHB cylinders can release FPTO (and consequently
NO) for up to 1 month with relatively constant rate. The FPTO loaded PHB cylinders
with sustained FPTO delivery were implanted around left carotid artery of wistar rats,
pure PHB cylinders were implanted around right carotid artery as control. At 1 st , 4 th ,
and 10 th days after implantation arteries and cylinders have been isolated. The elevated
levels of the main metabolic products of NO, nitrites and nitrates, in arterial tissues
were observed that indicates the possibility of application of this system for produc-
tion of physiological model of NO prolonged action on arterial tissues in vivo [24,
130, 131].
KEYWORDS
Biodegradation
Cell culture
Enzymatic degradation
Polylactic acid
Scanning electron microscopy
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