Biomedical Engineering Reference
In-Depth Information
reported that while drug release occurs mainly through diffusion
from the polymer matrix in the early phases, in the later phases,
drug release is mediated through both diffusion of the drug and
degradation of the polymer matrix [
21
]. Polymer degradation is
influenced by the polymer composition (lactide:glycolide ratio),
intrinsic viscosity and molecular weight, and crystallinity
[
27
,
33
]. Hence, selection of a suitable polymer from a wide
variety of PLA/PLGA polymers available becomes critical.
Polymer composition
: The more hydrophilic the polymer, more
rapid is its degradation [
34
,
35
]. The hydrophilicity is deter-
mined by copolymer composition. Glycolic acid, being more
hydrophilic than lactic acid, PLGA copolymers with higher
glycolide content are more hydrophilic and have a faster degra-
dation rate due to higher water uptake [
34
-
37
]. Generally, if
drug release up to 4-6 weeks is desired, PLGA 50:50 with low
to medium molecular weight (e.g., Resomer
®
RG 502 or 503)
can be used and if a slower release is required, PLGA with a
higher lactide/glycolide ratio (e.g., PLGA 65:35, PLGA 75:25,
or PLGA 85:15) or PLA can be used [
33
,
38
].
Polymer molecular weight
: In general, for a particular lactide/
glycolide composition of PLA/PLGA polymer, employing
high molecular weight polymers has been found to decrease
their degradation rate, thereby sustaining drug release [
27
,
32
,
36
,
37
,
39
].
Polymer crystallinity
:
L
-PLA and PGA are crystalline while
D
,
L
-PLA is amorphous [
40
]. In general, crystalline polymers are
able to sustain drug release for longer periods of time because
they are degraded at a slower rate compared to semi-crystalline
and amorphous polymers [
27
,
41
].
Polymer concentration
: Increasing the polymer concentration
increases the viscosity of the polymer giving rise to a dense and
compact internal structure that prevents drug diffusion to
external phase during the evaporation step [
42
]. Generally,
higher drug loading can be achieved by increasing the polymer
concentration.
Polymer end group
: The nature of the end group of the polymer
chain affects the degradation rate of the polymer by controlling
the water uptake by the polymer. Hydrophilic end groups such
as free carboxyl groups exhibit faster degradation rates
than hydrophobic end groups such as ester or alkyl ester groups
[
43
,
44
]. For instance, Resomer
®
RG 503H which is acid
terminated degrades faster than Resomer
®
RG 503 which is
ester terminated.
It should be noted that apart from the polymer properties
discussed above, nanoparticle size, pH, ionic strength, and
temperature of release medium also affect the polymer degra-
dation [
45
,
46
].
