Polyhydroxyalkanoates as Packaging Materials: Current Applications and Future Prospects - Polyhydroxyalkanoate (PHA) Based Blends, Composites and Nanocomposites - page 201

injection moulded P(3HB) plaques and hydroxyapatite/PHB composites into
femoral defects in New Zealand White rabbits; 12 months later no implant
resorption had occurred while new bone was formed adjacent to the im-
plant, with up to 80% of the implant's surface lying in direct apposition to
new bone. 75 L ¨ bler et al. tested PHB patches for the gastrointestinal tract in
a rat model. 76 Asymmetric PHB patches were sutured onto the stomach wall
and failed to induce fibrosis or a strong inflammatory response. 76
P(3HB-co-3HV) has been investigated for potential use in a diverse range of
medical applications including bone repair implants, medical sutures, car-
diovascular stents and as drug carriers. 77,78 Wu et al. have reported that
solvent cast P(3HB-co-3HV) films fabricated from commercial supply were
contaminated with lipopolysaccharide (LPS). 79 The authors report that these
'unpurified' films induced macrophage activation resulting in expression of
pro-inflammatory tumour necrosis factor (TNF) and interleukin-6 (IL-6)
during in vitro studies. 79 However, Foster and coworkers applied a cell cycle
approach to investigate the influence of the biomaterial on olfactory
ensheathing cells (OECs) and mesenchymal stem cells (MSCs) and found
that significantly higher percentages of cells were cycled at the synthesis (S)
phase of the cell cycle when cultivated on P(3HB-co-3HV) films compared
to P(3HB), with MSCs more susceptible than OECs. 80,81 Furthermore,
Chaput et al. studied P(3HB-co-3HV) patches, with various loadings of
hydroxyvalerate, implanted intramuscularly in sheep for a lengthy 90 weeks. 82
After an initial inflammatory response observed at one week, the reaction
decreased. After 11 weeks, the capsule at the interface between the polymers
and muscular tissue consisted primarily of connective tissue cells that
were well vascularised with highly organised, orientated fibres. In addition,
fibroblastic cells were observed, aligned in parallel with the biopolymer
surface. 82

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8.8.2 PHAs for Drug Delivery
The properties of PHA biocompatibility and degradability in mammalian
systems have been utilised for packaging of therapeutic agents that can
subsequently serve as drug delivery agents and carriers in blood. 83 The
challenges facing the effective application of PHAs for drug delivery include
(a) targeted delivery and (b) controlled or sustained release of the active drug
to the target region. A drug 'packaged' using a PHA-based carrier would take
advantage of the degradation rate of the PHA in order to effect sustained
delivery of the drug payload. The breakdown of PHAs in mammalian systems
is predominantly through chemical hydrolysis where crystallinity and mo-
lecular weight play important roles. Therefore, whilst carriers produced from
sclPHAs, such as PHB and P(3HB-co-3HV), are considered porous and highly
crystalline (properties that would lend a carrier to deliver its payload too
quickly), mclPHAs, such as polyhydroxyoctanoate (PHO), being compara-
tively more amorphous with a lower crystallinity and melting point, appear
more suited to drug delivery. 83