Degradation Profile of Electrospun PLGA MatrixDegradation Profile of Electrospun PLGA Matrix Dana DolevDana Dolev11, Oded Nissan, Oded Nissan22

1 – Bio Medical Engineering Department, Tel Aviv University; 2 – Optonol Ltd.1 – Bio Medical Engineering Department, Tel Aviv University; 2 – Optonol Ltd.

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

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.

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.

Materials1. 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']4.50:50 mixture of material A and material B ['material D']5.50:50 mixture of material A and material C ['material E']

Preparation of electrospun fiber matrixA 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 #2 – In-Vivo study•Carried out on rodents’ eyes•The implants are histopathologicaly evaluated periodically.

ResultsResultsComparing degradation profiles

of the various materialsEffect of fiber size on matrix

degradation profile (material ‘A’)Comparing 'real time' and

'accelerated' tests (material ‘A’)Molecular Weight (Mw)

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5

time points (m)

mo

lecu

lar

wei

gh

t (g

/mo

l*10

^4) 37º

48º

Matrix Mass Change

0

20

40

60

80

100

120

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5

time points (m)

matr

ix m

ass (

%)

37º

48º

Ultimate Tensile Force

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5

time points (m)

ult

ima

te t

en

sile

fo

rce

(N

)

37º

48º

In-Vivo Study Results- Histopathological Sections

3 months – no degradation 6 months – degradation begins 12 months – full degradation

Molecular Weight (Mw)

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

0 0.5 1 1.5 2 2.5 3 3.5

time points (months)

mo

lecu

lar

wei

gh

t (g

/mo

l*10

^4)

Material A

Material B

Material C

Material D

Material E

Matrix Mass Change

0

20

40

60

80

100

120

140

160

180

200

0 0.5 1 1.5 2 2.5 3 3.5

time points (months)

matr

ix m

ass (

%)

Material A

Material B

Material C

Material D

Material E

Ultimate Tensile Force

0

2

4

6

8

10

12

14

16

18

0 0.5 1 1.5 2 2.5 3 3.5

time points (months)

ult

imate

ten

sile f

orc

e (

N)

Material A

Material B

Material C

Material D

Material E

Conclusions1.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.

Molecular Weight (Mw)

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

1.10

1.20

1.30

0 1 2 3 4 5 6 7

time points (m)

mo

lecu

lar

wei

gh

t (g

/mo

l*10

^4)

1.4 µm

3.5 µm

4.6 µm

11µm

13µm

15µm

Matrix Mass Change

50

60

70

80

90

100

110

120

130

140

150

0 1 2 3 4 5 6 7time points (m)

mat

rix

mas

s (%

)

1.4 µm

3.5 µm

4.6 µm

11µm

13µm

15µm

Ultimate Tensile Force

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00

8.00

9.00

0 1 2 3 4 5 6 7

time points (m)

ult

ima

te t

en

sile

fo

rce

(N

)

1.4 µm

3.5 µm

4.6 µm

11µm

13µm

15µm