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