study of structural modifications in poly(l-lactide) induced by high-energy...
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STUDY OF STRUCTURAL MODIFICATIONS IN POLY(L-LACTIDE)
INDUCED BY HIGH-ENERGY RADIATION
Dejan Milicevic and Edin Suljovrujic
Department of Radiation Chemistry and Physics, „VINČA" Institute of Nuclear Sciences -
National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
30th Summer School and International Symposium on the Physics of Ionized GasesAugust 24-28, 2020
Coronary Heart Disease (CHD)
- Coronary heart disease is the leading cause of death worldwide.
- Plaque in blood accumulates against the walls of the coronary
artery, which returns oxygen rich blood from lungs to heart. If left
untreated, it could lead to blood clots/heart attacks.
CHD treatment options:
Surgery (Bypass, High Risk)
Medication treatment (Less Effective)
Angioplasty
Angioplasty:
Minimally invasive procedure; heart stents,
usually made of a metal mesh, are inserted
into the body thus enabling the blood flow
increase.
Possible problems with metalic and metal-mesh stents:
- Effective, but often delay natural healing process of the arteries.
- If metal mesh is not placed in suitably, plaque may build up on the
stent, eventually killing 1 in 200 patients in procedure.
Possible solution:
- The use of a biodegradable polymer drug
eluting stent (DES) mainly produced out of
biodegradabile polylactide. These stents
are designed to completely dissolve into the
bloodstream within 2-3 years after procedure
(no need for additional surgical procedure)
and are found to be safer than metal stents
(the risk of stent thrombosis and heart attack
are significantly reduced).
The sterility of the product - one of the main concerns with
respect to the successful application of implanted biomaterial
- Several different sterilization procedures were proposed.
- In the case of polymer implants, their high sensitivity to heat, moisture and
radiation should be taken into account when a particular method is applied.
- Amongst conventional methods, dry and moist heat sterilizations are not
suitable for thermosensitive polymers as they lead to thermal degradation and
structural changes.
- Ethylene oxide (EO) is broadly used for polymeric devices although including
drawbacks such as its toxicity, changes in morphology and the presence of gas
residues, which requires long aeration time.
- Contrary, due to the excellent penetration characteristics of high-energy
ionizing radiation (in the form of gamma radiation from a suitable radioisotopic
source such as 60Co or of electrons energized by a suitable electron
accelerator). Radiation sterilization eliminates problems which may appear
with other methods like high temperature, need for quarantine, problems
associated with residuals and EO gas penetration, uniformity of sterilization etc.
Problems with the radiation sometimes evolve as a result of its damaging effects
on materials.
Experimental: Materials
Polylactide (PLA): linear thermoplastic aliphatic polyester derived from renewable
resources such as corn starch. It is extensively employed as a biomaterial in numerous
applications including tissue engineering three-dimensional scaffolds, implantable medical
devices and carriers in controlled drug delivery systems, to the environmentally friendly
packaging ones. Degradation of this biocompatible and biodegradable polymer lead to non-
toxic products as it enters the Kreb’s cycle inside the human body and is eventually removed
as carbon dioxide and water.
(a) (b) (c)
PLA exists in two stereo-isomeric forms: (a) D-PLA (PDLA)
and (b) L-PLA (PLLA), and (c) a mixture of D- and L-lactic
acid also exists as D,L-PLA (PDLLA)
Polymer obtained from L-lactide - PLLA was used in this
study: Commercial granular poly L-lactide (Fluka, Germany;
Mw=100,000, Mn=60,000)
The polymers, which are derived from
optically active D and L monomers, are
semi-crystalline while the optically inactive
D,L-PLA is amorphous. Generally, L-PLA
is preferred in applications where high
mechanical strength and toughness are
required, e.g. sutures and orthopedic
devices. In contrast, due to the amorphous
nature of D,L-PLA, it is usually considered
for applications such as drug delivery
systems, as it is important to have a
homogeneous dispersion of the active
species within a monophasic matrix.
Experimental methods:
1. Scanning electronic microscopy (SEM)
2. Gel permeation chromatography (GPC)
3. Differential scanning calorimetry (DSC)
4. Wide-angle X-ray diffraction method (WAXD)
5. Fourier transform infrared (FTIR) spectroscopy
6. Electron spin resonance (ESR) spectroscopy
Results and discussion
Scanning electronic microscopy (SEM)
Figure 1. SEM images of (un)irradiated samples obtained by: (a-c) quenching
from the isotropic melt in the ice-water mixture and (d-f) slow cooling to the
room temperature keeping the sample between the press platens;
100m
100m 100m10m
10m 10m
(d)
(a) 0 kGy (c) 300 kGy
0 kGy
(b) 50 kGy
(e) 0 kGy (f) 300 kGy
Gel permeation chromatography (GPC)
2*104
105
Mn
[g/m
ol]
Absorbed dose [kGy]
(a)
0 100 200 300
quenchedslowly cooled
6*104
M n
,0/M
n,t
Absorbed dose [kGy]
0 100 200 3000
2
4
6
quenched
slowly cooled
(b)
Figure 2. (a) Number average molecular weight (Mn) as a function of absorbed
dose for quenched and slowly cooled samples and (b) Mn,0/Mn,t ratio as a
function of absorbed dose, where Mn,0 and Mn,t are molecular weights of the
unirradiated and irradiated samples, respectively.
Figure 3. DSC heating thermograms of (a) quenched and (b) slowly cooled
samples for various absorbed doses.
(a)
50 kGy
0 kGy
100 kGy
300 kGy
320 360 400 440 480
T[K]
DH
/Dt
[Jg
-1s
-1]
2 Jg-1s-1
En
do
(b)
50 kGy
0 kGy
100 kGy
300 kGy
2.5 Jg-1s-1
En
do
320 360 400 440 480
T[K]
DH
/Dt[J
g-1
s-1
]
Differential scanning calorimetry (DSC)
slowly cooledquenched
12 3
Figure 4. (a) Melting (ΔHm) and cold crystallization (ΔHcc) enthalpy and ΔHo = ΔHm
- ΔHcc of quenched samples as a function of absorbed dose and (b) ΔH0 enthalpy of
the quenched and slowly cooled samples.
Absorbed dose [kGy]
(a)
100 200 3000
En
tha
lpy [
Jg
-1]
DHm
DHO=DHm-DHCC
DHCC
10
20
30
40
50
60
Absorbed dose [kGy]
(b)
quenchedslowly cooled
En
thalp
y [
Jg
-1]
10
20
30
60
70
80
100 200 3000
quenched
Inte
nsit
y [
a.u
.]
2Ө ( o )10 20 30
(200)/(110)
(010)
(203)
(015)
5 x
20 40 60 80
(a)
50 kGy
0 kGy
100 kGy
300 kGy
(200)/(110)
(203)
10 20 30
(200)/(110)
(010)(203)
(015)
(b)
10 20 30
(c)
(d)
50 kGy
0 kGy
100 kGy
300 kGy
quenched
slowly cooled quenched
slowly cooled
Figure 5. WAXD spectra of unirradiated quenched and slowly cooled samples in the 2θ range: (a) 5°-90° and (b) 5°-35° (quenched samples
are presented magnified for clarity); the evolution of WAXD spectra with absorbed dose for (c) quenched and (d) slowly cooled samples.
Wide-angle X-ray diffraction method (WAXD)
Figure 6. Crystallinity of: (a) quenched and
slowly cooled samples obtained by DSC and
WAXD measurements, (b) quenched and
slowly cooled (un)annealed samples (in air, at
80 °C for 2 h after irradiation); (c) FWHM (B)
and crystal size as functions of absorbed dose.
DSC
quenched
slowly cooled
quenched an.
slowly cooled an.
0 50 100
20
40
60
80
Absorbed dose [kGy]
Cry
sta
llin
ity [
%]
(b)
0 50 100
20
40
60
80
DSC
WAXD
quenched
slowly cooled
Absorbed dose [kGy]
Cry
sta
llin
ity [
%]
(a)B
(°
)
0 100 200 3000,20
0,24
0,28
0,32
FWHM
Crystal size
26
30
34
38
Cry
sta
l s
ize
[n
m]
Absorbed dose [kGy]
(c)
Fourier transform infrared (FTIR) spectroscopy
Figure 7. FTIR spectra
of (a) unirradiated
quenched and slowly
cooled samples and
(b) quenched samples
for different absorbed
doses.Wavenumber [cm-1]
quenched
slowly cooled
Re
fle
cti
vit
y[a
.u.]
960 920 880 840
917868
954 860
(a)
50 kGy
0 kGy
100 kGy
300 kGy
1760 1720 1400 1300 1200 1100 1000
(b) quenched
r(CH3) + ν(C-COO)
δ(CH3); δ(CH)
ν(C-CH3); r(CH3)
ν(COC) + r(CH3)
ν(COC); ν(C-CH3)
1760 1720 1400 1300 1200 1100 1000
ν(C=O)
Electron spin resonance (ESR) spectroscopy
Figure 8. (a) ESR spectra of quenched samples (Qs); ESR
spectra of slowly cooled samples (SCs) for (b) short and (c)
prolonged period of time; (d) ESR spectra of SCs annealed
(SCA) for different periods of time
330 335 340
H [mT]
dI/
dH
(a.u
.)100 kGy(a)
T=20 oC
1 h4 h
10 h
1 h6 h
12 h
(b)
Qs
SCs
–C*(CH3)-
dI/
dH
(a.u
.)
330 335 340
0 h2 h8 h
1 h6 days
20 days
Annealing time
TO=80 oC
(d)
SCs
100 kGy
T =20 oC
100 kGy
(c)
H [mT]
SCA
Figure 9. Relative free radical concentration (FRC) as a function of (a) short and
(b) prolonged periods of time; (c) Relative FRC versus annealing time.
Rela
tive F
RC
(I/I 0
)
Time [h]
0 6 12
0.0
0.5
1.0
quenched
slowly cooled
(a)
Time [days]
0 10 20
0.0
0.5
1.0
(b)
SCs
0 5 10
0.0
0.5
1.0
Re
lati
ve
FR
C (
I/I0
)
Annealing time [h]
TO=80 oC
SCA
(c)
Re
lati
ve
FR
C (
I/I 0
)
100 kGy
CONCLUSIONS:
• Depending on the initial preparation conditions, the radiation-induced
changes in the structure and properties of PLLA, as well as the evolution of
free radicals, differ significantly.
• The low crystalline samples are found to be initially more susceptible to
the gamma radiation than the high crystalline ones.
• On the other hand, due to the presence of long-lived free radicals, the
high crystalline samples are more prone to the post-irradiation degradation.
In addition, the applied annealing treatment substantially reduces the
concentration of long-lived radicals, but can also induce additional
crystallisation.
• As the gamma radiation leads to quite foreseeable alterations of thermal
and morphological properties of PLLA, the radiation processing can be
applied with the aim of simultaneous tailoring of required functionality
(e.g. the rate of hydrolytic degradation) and achieving the sterility of final
products, especially for low sterilization doses where the observed
changes are small and tolerable (up to 25 kGy in most circumstances).
Thank you for your attention!
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