Degradation Profile of Electrospun PLGA Matrix
1
Dolev ,
Dana
Oded
2
Nissan
1 – Bio Medical Engineering Department, Tel Aviv University; 2 – Optonol Ltd.
Objectives
• Finding raw materials for electrospun matrices that
provide different degradation rates (hence fit different
medical applications).
• Studying the effect of fiber size on the degradation of
a fibrous matrix.
• Determining the quantitative connection between the
in vitro real time and in vitro accelerated tests
• Understanding the quantitative connection between
in vivo and in vitro degradation.
Introduction
• Electro spun fibers are used in various applications as
scaffolds for tissue engineering; carriers for drug
delivery system and wound dressing materials.
• Electrospinning is a polymer processing technique in
which a stream of a polymer solution is subjected to a
high electric field, resulting in formation of nano-micro
dimension fibers.
• Polylactide (PLA), polyglycolide (PGA), and their
copolymer polylactide-co-glycolide (PLGA) find wide
applications in the pharmaceutical and medicine
industries owing to their excellent biodegradation,
biocompatibility and nontoxic degradation products.
• The degradation profile of each of these materials has
great influence on their function in the medical
application. The degradation is affected by many
parameters.
Materials
1. Poly (lactide-co-glycolide acid) 75:25 ['material A']
2. Poly (D-L-lactide-co-L-lactide acid) 50:50 ['material B']
3. Poly (D-lactide-Glycolic acid) 60:40 ['material C']
4. 50:50mixture of material A and material B ['material D']
5. 50:50 mixture of material A and material C ['material E']
Preparation of electrospun fiber matrix
A syringe full of polymer solution was placed in the electrospinning machine. The machine was set
to a voltage of 20-30kV and the elctrospun fibers were collected on a metal collector.
Method #1 – In-Vitro study
• Performed both in a 37ºc (‘real time’) and 48ºc (accelerated) environments
• The samples are kept in pH controlled environment
• The samples are tested periodically for various parameters
Method #2 – In-Vivo study
• Carried out on rodents’ eyes
• The implants are histopathologicaly
evaluated periodically.
Results
Comparing degradation profiles
of the various materials
Effect of fiber size on matrix
degradation profile (material ‘A’)
Molecular Weight (Mw)
Material A
Material B
0.80
Material C
Material D
0.60
Material E
0.40
0.20
0.00
1
1.5
2
2.5
3
11µm
1.4
µm
13µm
3.5 µm
15µm
4.6
µm
0
3.5
1
2
3
150
200
Material B
140
180
Material C
Material D
130
160
140
Material E
120
100
80
60
50
2.5
3
3.5
11µm
1.4 µm
13µm
3.5 µm
2
2.5
3
1
2
3
4
5
6
ultimate tensile force (N)
Material C
14
Material D
12
Material E
10
8
6
4
2
2.5
3
3.5
5
5.5
6
6.5
5.5
6
6.5
60
37º
48º
40
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
time points (m)
Ultimate Tensile Force
9.00
8.00
8.00
7.00
11µm
1.4
µm
6.00
13µm
3.5
µm
5.00
15µm
4.6
µm
4.00
3.00
2.00
1.00
7.00
37º
48º
6.00
5.00
4.00
3.00
2.00
1.00
0.00
0
4.5
80
7
9.00
Material B
4
100
0
0
Material A
3.5
20
Ultimate Tensile Force
16
ultimate tensile force (N)
1.5
time points (m)
18
2
1
0
Ultimate Tensile Force
1.5
0.5
15µm
4.6 µm
tim e points (m onths)
1
0.00
120
80
60
0.5
0.20
Matrix Mass Change
90
0
0
0.40
time points (m)
100
20
2
0.60
0
110
70
1.5
7
120
40
1
6
0.80
Matrix Mass Change
Material A
matrix mass (%)
matrix mass (%)
Matrix Mass Change
0.5
5
37º
48º
1.00
time points (m)
tim e points (m onths)
0
4
1.20
matrix mass (%)
0.5
molecular weight (g/mol*10^4)
1.00
Molecular Weight (Mw)
1.40
1.30
1.20
1.10
1.00
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
ultimate tensile force (N)
molecular weight (g/mol*10^4)
1.20
molecular weight (g/mol*10^4)
Molecular Weight (Mw)
1.40
0
Comparing 'real time' and
'accelerated' tests (material ‘A’)
0.00
0
1
2
3
4
5
6
7
time points (m)
tim e points (m onths)
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
5.5
6
6.5
time points (m)
In-Vivo Study ResultsHistopathological
Sections
3 months – no degradation
6 months – degradation begins
12 months – full degradation
Conclusions
1.The studied materials have different degradation rates; material B has the lowest rate while material E has the highest.
2.The fiber diameter (at the studied range) does not significantly affect the degradation profile of the matrix.
3.The ‘acceleration factor’ obtained from this study was approx. 4 (=the degradation is 4 times faster in 48ºc than in 37ºc).
4.The in vivo and in vitro degradation profiles of the matrix performed strong connection; The in vivo degradation is
apparently slightly slower that the in vitro degradation.