BIODEGRADABLE POLYMERS

CONTENTS
• Introduction
• Definition
• Characteristics of biodegradable polymers in drug delivery
system
• Classification of biodegradable polymers
• Factors affecting biodegradation of polymers
• Advantages of biodegradable polymers
• Applications of biodegradable polymers
• Conclusion
• References
INTRODUCTION
• Polymer
Polymers are defined as very large molecules consisting of many
repeating units & are formed by a processes called polymerization, which
links together smaller molecules known as monomers.

• Monomers can be linked together in

various ways to give ………
➢ Linear
➢ Branched
➢ cross linked polymers
• Based on biodegradability polymers are classified as:
1. Biodegradable polymers
eg: collagen, poly glycolic acid etc.,
2. Non biodegradable polymers
eg: poly vinyl chloride, polyethylene etc.,
BIODEGRADABLE POLYMER

• Definition :
Defined as polymers comprised of monomers linked to one
another through functional groups and have unstable links in the
backbone.

• Broken down into biologically acceptable molecules that are

metabolized and removed from the body via normal metabolic
pathways.
IDEAL CHARACTERISTICS

• Inert
• Permeability
• Biodegradability
• Bio-compatilibility
• Tensile strength
CLASSIFICATION
1. Based on mechanism of release of drug
2. Based on type of degradation
3. Based on the source
[Link] on the mechanism of release:

• Slow dissolution and erosion by hydrolysis

• Water insoluble polymers degradation of pendent group

without backbone cleavage.

• Water insoluble polymer degrades to water-soluble products

by backbone cleavage
 Biodegradable Polymers
Type I
x
H2O soluble x x
Swelling
Dimensional stability x x

Type II
H2O insoluble
Chemical change C C C C

No backbone O OR O OH O OR O O-

cleavage
Type III
x x

H2O insoluble x x x x

Chemical cleavage x x x x 30

MW↓
 Mechanism of Biodegradable Polymers

BIODEGRADATION

ENZYMATIC
DEGRADATION HYDROLYSIS COMBINATION

BULK EROSION SURFACE EROSION

2. Based on type of degradation

• Bioerosion – which contains both physical

(dissolution) and chemical (backbone cleavage)
process.
• Chemical degradation
Types of bioerosion
• Bulk erosion
• Surface erosion
o Bulk erosion:
▪ Degradation takes place through
out the whole of the sample
▪ Ingress of water is faster than
the rate of degradation
Eg :Polylactic acid (PLA)
Polyglycolic acid (PGA)
o Surface erosion
▪Sample is eroded from
the surface
▪Mass loss is faster than
the ingress of water into
the bulk
Eg :Polyanhydrides,
polyorthoesters
Chemical degradation

• Chemical degradation - mediated by water, enzymes,

microorganisms TRANSFORMATION OF SIDE CHAINS

CLEAVAGE OF CROSSLINKS

CLEAVAGE OF BACKBONE
[Link] on the source

• Synthetic biodegradable polymers:

eg: Aliphatic poly(esters)
Polyanhydride
Polyphosphazene
Pseudo poly aminoacid
Poly(orthoesters) etc.,
• Natural biodegradable polymers:
eg: Albumin
Collagen
Gelatin etc.,
Synthetic biodegradable polymers
• Aliphatic poly(esters)
• These are prepared by ring opening and polymerization of cyclic ester.
• Aliphatic polyesters include:
POLY (GLYCOLIC ACID) ---(--O—C-CH2---)n
POLY (LACTIC ACID) --(--O---C—CH---)n
POLY (CAPROLACTONE) --(--O—C---(CH2)5---)n
 Lactide /glycolide polymers:
• Most widely used biodegradable polymers
• Lactide/glycolide are the simplest aliphatic polyester
➢Biodegradation :
o Undergo biodegradation by bulk erosion.
o Cleaved by hydrolysis to monomeric acids and eliminated
through kreb’s cycle.
o Enzymatic degradation is also reported.

Esterase, pronase, bromelain

Applications

o Used to deliver drugs in the form of microspheres, implants

etc.,
o Examples of drugs delivered include steroid hormones,
antibiotics, anti cancer agents etc.,
Poly ε caprolactone
• semi-crystalline polymer
• slower degradation rate than PLA
• remains active as long as a year for drug delivery
➢Biodegradation:
o Occurs in two phases:
o First phase: hydrolytic chain scission of the ester linkage
o Second phase: decrease in the rate of chain scission and onset of weight
loss due to:
1. Diffusion of small mol wt polymer
2. Breakup of polymer mass to produce smaller particles
Applications:

Drug delivery applications of PCL includes:

- Cyclosporin in the form of nanoparticles
- Ciprofloxacin in the form of dental implants
Poly anhydrides

• Compression and injection moulding methods are employed to formulate

matrices bearing drug.

➢ Biodegradation:
• Degrades by surface erosion
• Carboxylic anhydride bond in the polymer chain is responsible for fast
erosion.
• Degradation is faster in basic than acidic media.
Applications:

o Suitable for short term drug delivery

o Used for vaccination and localized tumor therapy.
polyphosphazenes
• Hydrolytic stability/instability is determined by change in side group
attached to macromolecular backbone.
• Based on side chain these are of 3 types:
▫ Hydrophobic phosphazenes
▫ Hydrophilic phosphazenes
▫ Amphiphilic phosphazenes
Applications:

▪ Used in the construction of soft tissue prosthesis, tissue like

coatings, as material for blood vessel prosthesis.
▪ Used for immobilization of antigen or enzyme
Poly orthoesters
• These have acid- labile linkages in their backbone.
• Acid excipients causes fast erosion whereas basic excipients
causes long term erosion.
➢Application:
o Used in contraceptive steroid bearing bioerodible polymer
Natural biodegradable polymers
• Natural polymers are an attractive class of biodegradable
polymers as they are:
▫ Derived from natural sources
▫ Easily available
▫ Relatively cheap
Collagen
• Prime function is to check tissue deformation and avoid
mechanical failure.
Advantages:
✓It is a major structural protein in animals
✓It is used as sutures, Dressings, etc.
✓Readily isolated & purified in large quantities.
✓Can be processed in variety of forms.
Cont…
Disadvantages
✓Poor dimensional stability.
✓Variability in drug release kinetics.
✓Poor mechanical strength.
Application:
• Majorly used in ocular drug delivery system
Albumin
• It is a major plasma protein component.
• It accounts for more than 55% of total protein in human plasma.
• It is used to design particulate drug delivery systems.
 Cont…
Factors Affecting Drug Release From Albumin Microspheres
• Physicochemical properties and the concentration of the
drug.
• Interaction between the drug and the albumin matrix.
• Size and density of microspheres.
• Nature and degree of cross-linking.
• Presence of the enzymes and pH in the environment.
Application:

• Albumin micro-spheres are used to deliver drugs like Insulin,

Sulphadiazene, 5-fluorouracil, Prednisolone etc.
• It is mainly used in chemotherapy, to achieve high local drug
concentration for relatively longer time.
Gelatin
• Heterogeneous products obtained by hydrolytic extraction of
treated animal collagen.
• Physicochemical properties depends on the source of collagen,
extraction method and thermal degradation.
➢Applications:
➢Employed as matrix and as coating material.
➢Gelatin micropellets are used for oral controlled delivery of
drugs.
Dextran

• Dextran is a complex branched polysaccharide made of many glucose

molecules joined into chains of varying lengths.
• It consists of α-D-1,6-glucose-linked glucan with side-chains linked to the
backbone of Polymer.
• [Link] ranges from 1000 to 2,00,000 Daltons

Applications:
• Used for colonic delivery of drug in the form of gels
 CHITOSAN
• It consists of B-1-4 linked 2 amino-2-deoxy gluco –pyranose
moieties.
• Commercially manufactured by N-deacetylation of Chitin
which is obtained from Mollusc shells.
• It is soluble only in acidic pH i.e. when amino group is
protonated.
• Thereby it readily adheres to bio membranes.
• It is degraded mainly by Glycosidases & lysozymes.

ADVANTAGES
Free availability, Biocompatibility, Biodegradability
Bioadhesive, unique properties.
FACTORS AFFECTING BIODEGRADATION
OF POLYMERS
➢ Morphology factors
• Shape & size
• Variation of diffusion coefficient and mechanical stresses
➢ Chemical factors
• Chemical structure & composition
• Presence of ionic group and configuration structure
• Molecular weight and presence of low molecular weight compounds
➢ Physical factors
• Processing condition
• Sterilization process
ADVANTAGES OF BIODEGRADABLE
POLYMERS
• Localized delivery of drug
• Sustained delivery of drug
• Stabilization of drug
• Decrease in dosing frequency
• Reduce side effects
• Improved patient compliance
• Controllable degradation rate
APPLICATIONS OF BIODEGRADABLE
POLYMERS
• Polymer system for gene therapy

• Biodegradable polymer for ocular, tissue engineering, vascular,

orthopedic, skin adhesive & surgical glues.

• Bio degradable drug system for therapeutic agents such as anti

tumor, antipsychotic agent, anti-inflammatory agent.
BIODEGRADABLE POLYMERS IN
ADVANCED DRUG DELIVERY
• POLYMERIC MICELLES: used to deliver therapeutic agents.

• HYDRO GELS: these are currently studies as controlled release

carriers of proteins & peptides.

• The polymer matrix can be formulated as either micro/nano-spheres,

gel, film or an extruded shape.
The shape of polymer can be important in drug release kinetics.
Conclusion
• Numerous synthetic biodegradable polymers are available and still being
developed for sustained and targeted drug delivery applications.
• Biodegradable polymers have proven their potential for the development of
new, advanced and efficient DDS and capable of delivering a wide range of
bioactive materials.
• However, only few have entered the market since many drugs faces the
problem of sensitivity to heat, shear forces and interaction between
polymers.
• These problems can be overcome by fully understanding the degradation
mechanism to adjust the release profile.
References
• Controlled and Novel Drug Delivery by N. K. Jain;
pg no: 27-51.
• Controlled Drug Delivery Concepts and Advances
by [Link] Roop [Link]; pg no:97-155.
• Novel Drug Delivery Systems by Yie W Chien; second
edition; pg no:32-34.
• Design of Controlled Release Drug Delivery System by
Xiaoling Li, Bhaskara R. Jasti; pg no:271-303.
• International Journal of Pharma Research and Development;
volume 2; issue8(002).
• Advanced Drug Delivery reviews;56(2004);pg no: 1453-1466
by Gesine winzenburg et. al.
If your boss comes to you
and says:
There will not be any salary rise for
this year………..
There are no bonuses either………
All overtime has been cancelled
No expenses will be paid.....
And there will be no additional
healthcare!
What will your reaction be ?

…………………….!!