Page 82 - Biodegradable Polyesters

60 3 Microbial Synthesis of Biodegradable Polyesters: Processes, Products, Applications

issues for PHBHHx as an implant biomaterial is the non-toxicity and lack of
immunostimulation properties of its degradation products including monomers
2+
and oligomers; they even stimulate the Ca -channel activation and promote
regeneration of damaged tissues.
Thanks to the successful approval of P4HB as an implant biomaterial, more
PHA-based biomaterials should to go into clinical trials shortly. Because of the
diversity of PHA materials, one can expect PHAs to become a family of bioimplant
materials with rich applications.

3.8.2.3 PHAs as Drug Delivery Carrier
Homo- and copolymers of lactate and glycolate are often used in commercially
available sustained release products for drug delivery. However, lactate and gly-
colate copolymers are degraded by bulk hydrolysis. Thus drug release cannot be
controlled fully. In the early 1990s, PHAs became candidates for use as drug car-
riers because of their biodegradability, biocompatibility, and their degradation by
surface erosion.
The potential of matrices produced by direct compression of PHBV for oral
administration has been proven with the benefits of simplified processing over
alternative sustained release technologies. Increasing the polymer molecular mass
caused an increased rate of sulfamethizole release from irregularly shaped PHB
microparticles. Comparing this with the in vitro and in vivo release of the anti-
cancer agent lomustine from PHB and PLA microspheres as potential carriers for
drug targeting, it was discovered that the drug was released from the PHB micro-
spheres faster. Incorporation of ethyl or butyl esters of fatty acids into the PHB
microspheres increased the rate of the drug release.
Only PHB and PHBV have been studied for controlled drug release so far, it is
expected that other PHA family members with diverse properties will bring more
control release properties for the drug release field. This area still has potential for
exploitation.

3.8.3
Fine Chemical Industry: PHA Chiral Monomers

More than 120 different structures of carboxylic acids hydroxylated at the
3-, 4-, 5-, or 6-position, all in the (R)-configuration if they possess a chiral center
at the position of the hydroxyl group, have been reported in PHAs with an
increasing number of new monomers being discovered [63]. In addition, if the
cells are under carbon limitation, the accumulated PHA can be degraded to the
monomers and can be reutilized by the bacteria as a carbon and energy source
which can also serve to produce PHA monomers. Because of the chiral purity,
modifiable –OH and –COOH groups, and some other special characteristics,
PHA monomers have attracted much attention in industry and academic areas.
The technology needed for production of PHA monomers by chemical synthesis,
biotransformation, chemical degradation, and enzymatic degradation has now
been developed.