New Trends in Polymers - Progress in Organic and Physical Chemistry: Structures and Mechanisms - page 209

¿ lms in contact with blood did not activate the hemostasis system at the level of cell
response, but they did activate the coagulation system and the complement reaction
[90].
The high biocompatibility of PHB may be due to several reasons. First of all, PHB
is a natural biopolymer involved in important physiological functions both prokary-
otes and eukaryotes. The PHB from bacterial origin has property of stereospeci¿ city
that is inherent to biomolecules of all living things and consists only from residues of
D(-)-3-hydrohybutyric acid [91]. Low molecular weight PHB (up to 150 resides of
3-hydrohybutyric acid), complexed to other macromolecules (cPHB), was found to
be a ubiquitous constituent of both prokaryotic and eukaryotic organisms of nearly all
phyla [92-96]. Complexed cPHB was found in a wide variety of tissues and organs
of mammals (including human): blood, kidney, vessels, nerves, vessels, eye, brain, as
well as in organelles, membrane proteins, lipoproteins, and plaques. The cPHB con-
centration ranged from 3 to 4 —g/g wet tissue weight in nerves and brain to 12 —g/g
in blood plasma [97, 98]. In humans, total plasma cPHB ranged from 0.60 to 18.2
mg/l, with a mean of 3.5 mg/l. [98]. It was shown that cPHB is a functional part of ion
channels of erythrocyte plasma membrane and hepatocyte mitochondria membrane
[99,100]. The singular ability of cPHB to dissolve salts and facilitate their transfer
across hydrophobic barriers de¿ nes a potential physiological niche for cPHB in cell
metabolism [94]. However a mechanism of PHB synthesis in eukaryotic organisms is
not well clari¿ ed that requires additional studies. Nevertheless, it could be suggested
that cPHB is one of the products of symbiotic interaction between animals and gut mi-
croorganisms. It was shown, for example, that E.coli is able to synthesize low molecu-
lar weight PHB and cPHB plays various physiological roles in bacteria cell [96, 101].
Intermediate product of PHB biodegradation, D(-)-3-hydroxybutyric acid is also
a normal constituent of blood at concentrations between 0.3 and 1.3 mM and contains
in all animal tissues [102, 103]. As it was noted that PHB has a rather low degradation
rate in the body in comparison to, for example, poly(lactic-co-glycolic) acids, that
prevent from increase of 3-hydroxybutyric acid concentration in surrounding tissues
[10, 13], whereas PLA release, following local pH decrease in implantation area and
acidic chronic irritation of surrounding tissues is a serious problem in application of
medical devices on the base of poly(lactic-co-glycolic) acids [104, 105]. Moreover,
chronic inÀ ammatory response to polylactic and polyglycolic acids that was observed
in a number of cases may be induced by immune response to water-soluble oligomers
that released during degradation of synthetic polymers [105-107].
16.3.3 Novel Drug Dosage Forms on the Base of PHB
An improvement of medical devices on the basis of biopolymers by encapsulating
different drug opens up the wide prospects in applications of these new devices with
pharmacological activity in medicine. The design of injection systems for sustained
drug delivery in the forms of microparticles (microspheres, microcapsules) prepared
on the basis of biodegradable polymers is extremely challenging in the modern phar-
macology. The fixation of pharmacologically active component with the biopolymer
and following slow drug release from the microparticles provides an optimal level
of drug concentration in local target organ during long-term period (up to several