Influence of the Processes Parameters on the Properties of The ...

Chapter 1.
Polylactide Based Bio-Materials
It is important to note that <strong>the</strong>re is not a linear relationship between <strong>the</strong> copolymer PLGA
composition and <strong>the</strong> mechanical and degradation properties <strong>of</strong> <strong>the</strong> materials. For example, a copolymer <strong>of</strong>
50% glycolide and 50% D,L-lactide degrades faster than ei<strong>the</strong>r homopolymer (cf. Table 1.4). All PLGAs are
ra<strong>the</strong>r amorphous than crystalline and show a glass transition temperature in <strong>the</strong> range <strong>of</strong> 40–60°C. Unlike
<strong>the</strong> homo-polymers <strong>of</strong> polylactide and polyglycolide which show poor solubilities, PLGA can be dissolved
by a wide range <strong>of</strong> common solvents, including chlorinated solvents, tetrahydr<strong>of</strong>uran, acetone or ethyl
acetate.
Table 1.4: Degradation times <strong>of</strong> common polylactides.
Polymer T g (°C) Degradation Time (Months)
PGA 35 − 40 6 to 12
P L LA 60 − 65 >24
P D,L LA 55 − 60 12 to 16
P D,L LGA 85:15 50 − 55 5 to 6
P D,L LGA 75:25 50 − 55 4 to 5
P D,L LGA 50:50 45 − 50 1 to 2
[Adhikari and Gunatillake, 2003]
PLGAs are approved copolymers which are used in a host <strong>of</strong> <strong>the</strong>rapeutic devices, owing to its
biodegradability and biocompatibility as a major component in biodegradable sutures, bone fixation nails
and screws [Moghimi et al., 2001; Gombotz and Pettit, 1995]. They are well-characterized copolymers, <strong>the</strong>ir
degradation sub-products are non toxic and <strong>the</strong>y provide controlled drug release pr<strong>of</strong>iles by changing <strong>the</strong>
PLGA copolymer ratio [Ghosh, 2004; Bala et al., 2004; Moghimi et al., 2001; Anderson and Shive, 1997;
Gombotz and Pettit, 1995]. PLGAs <strong>of</strong> different molecular weights (from 10 kDa to over 100 kDa) and
different copolymer molar ratios (50:50, 75:25 and 85:15) are available on <strong>the</strong> market. Molecular weight and
copolymer molar ratio influence <strong>the</strong> degradation process and release pr<strong>of</strong>ile <strong>of</strong> <strong>the</strong> drug entrapped. In
general, low molecular weight PLGA with higher amounts <strong>of</strong> glycolic acid <strong>of</strong>fers faster degradation rates
[Anderson and Shive, 1997].
3 Adjuvant and Fillers
3.1 Adjuvant
3.1.1 Structure <strong>of</strong> Hyaluronic Acid (HA)
Hyaluronic acid was first biochemically purified in 1934 by Meyer and Palmer, who discovered
this unique ‘polysaccharide acid <strong>of</strong> high molecular weight’ from <strong>the</strong> vitreous body <strong>of</strong> bovine eyes [Garg and
Hales, 2004c]. Since it is believed that <strong>the</strong> molecule <strong>the</strong>y isolated consisted <strong>of</strong> ‘an uronic acid, an amino
sugar, and possible a pentose, <strong>the</strong>y so named <strong>the</strong> substance ‘hyaluronic acid’ (HA) [Garg and Hales, 2004b].
They also reported that HA was not sulfonated; this meant that <strong>the</strong> molecule could be reproduced by a cell
that syn<strong>the</strong>sizes HA, including animals and bacteria [Varki et al., 1999].
Interestingly, HA also differs from o<strong>the</strong>r structurally related GlycosAminoGlycans (Chondroitin 4
and 6 Sulfate, Heparan Sulfate, etc) in that it can be syn<strong>the</strong>sized without attachment to proteins [Garg and
Hales, 2004c]. Hyaluronic acid also labelled hyaluronan is a simple, linear glycosaminoglycan composed <strong>of</strong>
repeating disaccharide units <strong>of</strong> β-1,4-glucuronic acid (GlcA) and β-1,3-N-acetylglucosamine (GlcNAc)
[Garg and Hales, 2004c]. Figure 1.6 shows <strong>the</strong> alternating β-1,3 and β-1,4 glycosidic linkages between
GlcA and GlcNAc. Polymers <strong>of</strong> hyaluronan can range in size from 5 to 20 000 kDa in vivo [Saari et al.,
1993].
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