Synthetic bioresorbable polymers - Durability and Reliability of Medical Polymers - page 107

5.4.3 In vitro and in vivo correlation
There is some contradiction between the results of previous studies concerning
the extent of the effect of enzymes on polylactide and polyglycolide
degradation. For example, vert et al . 27 reported no difference in degradation
between PLA50 (poly- d l l-lactide) and PLA100 (100% l l-lactide) in buffer
and esterases solutions. However, Mason et al . 74 reported a degradation
rate between two and six times higher for PLA50 in plasma that contains
enzymes compared with simple buffers.
Despite these results, many studies found in vitro and in vivo degradation
rates for a range of PGLA copolymers to be the same. 4,23,24

5.4.4 Crystallinity and polymer morphology
Crystallinity has a significant effect on the degradation rate of aliphatic
polyesters because it determines how easily water molecules can access the
ester linkages to cause chain cleavage.
Aliphatic polyesters can be random copolymers which are amorphous and
do not crystallise during degradation; homopolymers and block copolymers
can be semicrystalline or amorphous depending on processing; and polymers
in between are amorphous in the undegraded state but become more crystalline
as they degrade. Crystallisable polymers can be given different morphologies
by quenching or annealing before degradation. 15
li et al . 10,23 examined morphological changes of amorphous polymers
during degradation. In vitro investigations of PLA50 (poly- d , l -lactic acid) and
PLA37.5GA25 (75% d , l -lactide and 25% glycolide) demonstrated that the
polymers started and remained amorphous throughout degradation. However,
PLA75GA25 (75% l l-lactide and 25% glycolide) samples were crystalline
after 7 weeks degradation. H-NMR studies (proton-based nuclear magnetic
resonance spectroscopy) suggested that PLA and PLA/PGA copolymers all
degrade via the same mechanism but that the GA units on PLA/GA copolymers
constitute vulnerable points on the macromolecular chains, so that degradation
occurs preferentially on the GA bonds. This phenomenon was observed only
up to 12 weeks degradation, after which point the lactide-glycolide ratio
remained constant. li et al . concluded that the glycolide removal caused
crystallisation of the remaining lactide regions. The remaining glycolide was
then incorporated into the new crystals protecting glycolide from hydrolysis
after 12 weeks.
Gel permeation chromatography (GPC) and size exclusion chromatography
(SEC) tests were carried out on 100% l l-lactide (PLA100), 75% d , l -lactide
and 25% glycolide (PLA37.5GA25) and 50% d , l -lactide and 50% glycolide
(PLA25GA50) samples by Hakkarainen et al . 25 Results exhibited development
of a multimodal distribution in molecular weight during degradation for the
semicrystalline PLA100 samples, whereas the amorphous copolymers degraded

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