Homopolymers and copolymers of lactate and glycolate are widely used in commercially
available sustained release products for drug delivery. However, lactate and
glycolate copolymers are degraded by bulk hydrolysis; hence, drug release cannot be
fully controlled (Pouton and Akhtar 1996). In the early 1990s, PHA became candidates
for use as drug carriers owing to their biodegradability, biocompatibility, and
degradation by surface erosion (Gould et al. 1987). PHA used as a drug carrier was
reviewed in 1989 by Koosha et al (1989). 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 (Gould
et al. 1987). Increasing the polymer molecular mass caused an increased rate of sulfamethizole
release from irregularly shaped PHB microparticles (Brophy and Deasy
1986). When the in vitro release and the in vivo release of the anticancer agent lomustine
from PHB and PLA microspheres as potential carriers for drug targeting were
compared, it was found that drug was released from the PHB microspheres faster
(Bissery et al. 1985). Incorporation of ethyl esters or butyl esters of fatty acids into
the PHB microspheres increased the rate of drug release (Kubota et al. 1988).
So far only PHB and PHBV have been studied for controlled drug release. It is
expected that other PHA family members with diverse properties will bring more
controlled release properties for the drug release field. This is still an area remaining
to be exploited.
PHA granule binding protein PhaP is able to bind to hydrophobic polymers
(Wang et al. 2008b). A receptor-mediated drug-specific delivery system was developed
in this study based on PhaP (Fig. 5). The system consists of PHA nanoparticles,
PhaP, and ligands fused to PhaP. The PHA nanoparticles were used to
package mostly hydrophobic drugs, PhaP fused with ligands produced by overexpression
of their corresponding genes in Pichia pastoris or Escherichia coli was able
to attach to hydrophobic PHA nanoparticle. At the end, the ligands were able to pull
the PhaP–PHA nanoparticles to the targeted cells with receptors recognized by the
ligands. It was found in this study that the receptor-mediated drug-specific delivery