Seminar on Mechanism of Biodegradation of Polymers
Keyur Vasava…
Contents
Introduction to polymers
Definition of biodegradation
Eg. of biodegradation
Biodegradation mechanism
Erosion mechanism
Biodegradation of some polymers
Factors affecting polymer degradation
Factors that accelerate polymer degradation
References
Introduction Of Polymers
Polymers are very large molecules comprising of repeating units of small molecules, the monomer. The monomers can be linked together to generate linear, linear, branched or cross-linked polymers.
The biodegradable polymers can be defined as polymers comprised of monomers linked to one another through functional groups & have unstable linkages in the backbone.
The biodegradable polymers should be biocompatible, biosorbable and bifunctional.
Definition of Biodegradation
The term BIODEGRADATION is often used to denote “degradation occuring in the biological environment.”
A better definition is “ Gradual breakdown of a material mediated by a specific biological activity.”
Biodegradable Polymers Used for Medical Applications
Natural polymers
Fibrin
Collagen
Chitosan
Gelatin
Hyaluronan
Synthetic polymers
PLA, PGA, PLGA, Polyorthoesters …
Poly(dioxanone)
Poly(anhydrides)
Poly(trimethylene carbonate)
Polyphosphozenes ... Why Do We Prefer Synthetic Ones?
Predictable lot-to-lot uniformity
Free from concerns of immunogenicity
Reliable source of raw materials
PO LYM ER
D EGRAD ATI O N RATE
PGA
2-3 m ont hs
PLA PLA (L form)
> 2 year years s
PLA PLA (D L form)
12-16 2-16 mon m ontt h s
PLGA
1-6 m ont hs
Eg. Of B io d egradat io n
C ar ar b o n y l b o n d t o
O N
A.
S O
R1
C
H2O X
R2
O
R1
C
OH
+ HX
R2
Where X= O, N, S O
O
R1
C
Ester
O
R2
R1
C
O NH
Amide
R2
R1
C
S
Thioester
R2
O
B. R1
X
O
H 2O
C
X'
R1
R2
X
C
+
OH
HX'
R2
Where X and X’= O, N O O R1 R1
O
C
O
NH
R2
O
O
R1
C
X
O
H 2O
C
NH
R2
Urea
Carbonate C.
C
R2
R1
O
C
+
OH
HX
R2
C
Where X = N O ,
O
R1
C
O
O NH
R2
C
R1
Imide
O
C
O
R2
C
Anhydride Anh ydride
Biod egradable eg radable Fun c t ion al Gro up s H
Acetal:
H 2O O
R
C
O
R
R'
O
+
OH
H
H
C
O
OH
C
C
OH
H2O
C
OH C
C
H
H
OH
C
O
C
H
N i t r i l e
H2O
+
OH C
C
C==O
OH
H
H
H
H 2O R
R
C
OH
+
R'
R
R
C C
N
H
R
R
C
OR'
R
OH
+ HO
P
OR''
R
C H
OH
+ HO
R'
OR''
CN
H
C C
O
O
P
H
R
HO
H2 O
Polycyanocrylate
C
O
O RO
OH
H
H 2O
H 2N
Phosphonate
C
H H
H2 O
C C
R'
H
H R
OH
H
OH
C
OH
Ether
R'
OH
OH
H em iacet iacet al:
+
C
C O
OR''
H
CN
H
H 2O C C
R' O
OR'''
R
C H
CN C C
CN
H C O
OR''
H
OH
+
C C
R' O
OR'''
Biodegradation
Generally, polymer degradation occurs in 2 phases:
1. In first phase, water penetrates the bulk of the device d evice & attacks the chemical bonds in the amorphous phase leading to conversion of long polymer chains into shorter water-soluble fragments. 2. In second phase, there is a rapid loss of polymer mass due due to enzymatic attack & fragment metabolism. More specifically, degradation can be divided in 4 steps: 1) water sorption 2) reduction of mechanical properties 3) reduction of molar mass 4) weight loss
Biodegradation Mechanism Enzymatic degradation
Here, biodegradation of polymers takes place p lace by enzymes..
Enzymes like hydroxylase, oxygenase and various colonic bacterial enzymes like galactoronidase, etc. play a significant role in the polymer biodegradation.
b) H y d r o l y s i s
( d e p en e n d o n m a i n c h ai a i n st r u c t u r e : an an h y d r i d e > es est e r > carbon ate) ate)
Degradation by Erosion Surface erosion (poly (ortho) esters and
polyanhydrides)
Sample is eroded from the surface
Mass loss is faster than the ingress of water into the bulk
2. Bulk erosion (PLA, PGA, PLGA, PCL)
Degradation takes place throughout the whole of the sample
Ingress of water is faster than the rate of degradation
Polymer Degradation by Erosion
Eg. Of Erodible Matrices
(a) Surface-eroding
system
(b) Bulk-eroding
system
Bioerosion can be classified into 2 main types as follows: 1. Type Ι erosion: High molecular weight, water insoluble macromolecules are converted in to small, water soluble molecules by a hydrolytic cleavage of labile bonds in the polymer backbone.
The development of a useful system mandates that all degradation products be completely nontoxic. nontoxic.
2. Type II erosion:
In systems based on type II erosion, water-insoluble macromolecules are converted to water-soluble macromolecules by hydrolysis, ionization, or protonation of a pendant group.
Because no backbone cleavage takes place, the solubilization does not result in any significant change in molecular weight.
Biod Biod egrad at ion of PCL PCL
B iio od egradation of polyphosphozenes
Polyphosphozenes
Excreted
Metabolism
Factors Influence the Degradation Behavior Chemical
Structure and Chemical Composition:
Linear polymer chain structure is less degraded than branched structure because b ecause of less no. no . of entanglements en tanglements than branched structure.
If polymer is composed of more hydrophilic groups, then it is more degraded by hydrolysis.
Distribution of repeat units: If polymer has long monomers, then it decreases polymer strength due to decrease in no. of entanglements per chain, hence more biodegraded, while short monomers increase polymer strength. strength.
Molecular
Weight:
Low mol.wt. polymers are more degraded by microbes, as they are taken in by microbial cells, attached to coenz.coenz.A and metabolized within microbes.
Too large polymers have difficulty in entering the microbial cells.
Polydispersity:
Some polymers have different sequence and no. of monomers, which leads to diferent mass. This phenomenon is called polydispersity.
It indirectly affects degradation by affecting molecular weight.
Presence
of Ionic groups:
Presence of opposite ionic groups lead to attraction between monomers which increase strength of polymer, hence polymer is less degraded.
Presence of absorbed or adsorbed compounds: If water, ions, etc. are present as absorbed or adsorbed compounds, then they cause more degradation.
Morphology: If polymer is crystalline, then it is less degraded than amorphous, because only amorphous phase is accessible to permeants like water and susceptible to attack.
Storage
History:
If polymers have stored in environment where fungi, bacteria and their enzymes are present, then they consume polymers as food substances and thus, degradation increases at such place.
Target Site: At target site, if more bacteria are present, then degradation is faster , eg. colonic site.
Size: If polymer has small size, then larger surface is in contact with biological environment, hence, more degradation.
Factors That Accelerate Polymer Degradation More
hydrophilic end groups.
Less crystallinity.
More porosity.
Smaller device size.
