2. Biodegradable Polymer
Biodegradable polymers degrade within the body as
a result of natural biological processes.
They are broken down into biologically acceptable
molecules that are metabolized and removed from the
body via normal metabolic pathways.
3. Ideal Characteristics Of Polymers In
Biodegradable Delivery System
• Inert
• Permeability
• Biodegradability
• Bio-compatilibility
5. POLYMER DEGRADATION
The degradation is primarily the process of chain cleavage
leading to a reduction in molecular weight. On the other hand,
erosion is the sum of all processes leading to the loss of mass
from a polymer matrix.
Degradation Schemes
The degradation of the polymer can be through either bulk
erosion (as in poly(α-hydroxy esters)) or surface erosion (as
in polyanhydrides, poly(orthoesters)).
Generally Hydrophobic Polymers degraded by these
mechanisms.
Enzymatic degradation
Hydrolysis
6. Bulk Erosion : In this process
hydrolysis occurs throughout
the bulk of the polymer. The
matrix can disintegrate before
drug depletion, and a large
burst in rate of drug delivery
can take place.
Surface Erosion: In a surface
erosion process hydrolysis of
the polymer is confined to the
outer surface, and the interior
of the matrix remains
essentially unchanged.
7. Type I Erosion
It is evident with water-soluble
polymers cross-linked
to form a three-dimensional
network.
Erosion can occur by
cleavage of cross-links
(type IA) or cleavage of
the water-soluble
polymer backbone (type
IB)
8. Type II Erosion
It occurs with polymers that
were earlier water-insoluble
but converted to water-soluble
forms by hydrolysis, ionization
or protonation of a pendant
group.
Type III Erosion
High molecular weight, water-insoluble
macromolecules are
converted to small, water-soluble
molecules by a
hydrolytic cleavage of labile
bonds in the polymer
backbone.
9. Factors Influence the Degradation Behavior
Chemical Structure and Chemical Composition
Molecular Weight
Presence of Low Mw Compounds (monomer, oligomers,
solvents, plasticizers, etc)
Presence of Ionic Groups
Presence of Chain Defects
Configurational Structure
Morphology (crystallinity, presence of microstructure,
orientation and residue stress)
Processing methods & Conditions
Method of Sterilization
Storage History
Site of Implantation
Physiochemical Factors (shape, size)
Mechanism of Hydrolysis (enzymes vs water)
11. Lactide/Glycolide Polymers
POLY (GLYCOLIC ACID) ---(--O—C-CH2---)n
POLY (LACTIC ACID) --(--O---C—CH---)n
POLY (CAPROLACTONE) --(--O—C---(CH2)5---)n
First polymers used in medicine dated back to 1954.
Most commercialized class of Polymers
ex : ADRIAMYCIN®
Bio compatible & Bio resorbable
Synthesis & Co polymerisation can be easily done
t ½ ranges from weeks (PLA) to years (PCL).
APPLICATIONS : (1) Sutures, ligatures etc.
(2) DECAPEPTYL ® , LUPRON DEPOT ®
13. POLY PHOSPHO ESTERS
O
--(--P---O---R---O--)-- Poly (Phosphate )
OR1
O
--(--P---O---R---O--)-- Poly (Phosphonate)
R1
Highly Adjustable properties
Good Biocompatabilty
High Degradability
High Mol.wt gives good strength
14. Drug Release
Get degraded within 6 months
T1/2 is from 2 to 4 months..
Degradation products – phosphates & alcohol.
Applications
Paclitaxel, Cisplatin, Plasmid DNA.
Sterilisation & stability
Highly susceptible to hydrolysis in open air.
Should be stored in a desiccators.
Sterilization only by gamma irradiation.
15. POLY ANHYDRIDES
HO--[---(C—R1----C)n1-----O-----(C---R2---C-)n2--]n3---OH
General structure
• Two carboxylic groups at each end
• High Degradation rate
• Degrade by Surface Erosion
• Aromatic P.A’s are slower degrading
• Copolymerisation can control degradation rate
• Biological tests in Rabbits proved them Non-mutagenic
APPLICATIONS : 1) Peptides for osteomylites.
2) Protiens for brain tumour.
16. Drug Release
Mostly they degrade by Surface Erosion (S.E)
Their t1/2 is less than 30 days.
Due to S.E. proportion of drug released alters with
time.
Drug Stability
Primary amine containing drugs react at pH 7.2.
The above reaction is not seen below pH 5.0.
They are ideal when action is required for 1 week
They have more application as parentrals.
17. POLY OLEFINS
Properties
A polyolefin is a polymer produced from a simple olefin (also
called an alkene with the general formula CnH2n) as a
monomer.
Carbon Chain based Polymers.
They contain Double & Triple bonds extensively.
Presence of substituents like cyanoacryl groups enhance
degradation rate.
Introduction of vinyl group makes them more stable
ex : Teflon
Applications
1) Sutures, catheters, implants.
2) Membrane barrier for drugs.
18. POLY AMIDES
PROPERTIES :
A polyamide is a polymer containing monomers of amides
joined by peptide bonds.
These are generally called as ‘NYLONS’.
They are generally slow degrading.
By Introduction of copolymers like ‘L-Aspartic Acid', nearly
40% of polymer Is degraded within 1 week.
Mainly degraded In vivo by Non-specific ‘Amidases’
They are more stable when compared to other Polymers.
APPLICATIONS :
• Haemofiltration Membranes.
• Dressings, sutures etc.
19. ADVANTAGES
Play an essential role in Formulation of CDDS.
Patient compliance is improved.
Bio compatible.
Help in adjusting duration of action of drug.
Most of them are Inert.
Copolymerisation can be done.
DISADVANTAGES
Expensive.
Drug release cannot be 100% predicted.
20. NATURAL POLYMERS
These are the polymers obtained from natural resources, and
are generally non-toxic.
NATURAL POLYMERS
PROTEINS Polysaccharides
Ex: COLLAGEN
ALBUMIN
FIBRIN
Ex : DEXTRAN
CHITOSAN
STARCH
ADVANTAGES : 1) Readily & Abundantly Available.
2) Comparatively Inexpensive.
3) Non toxic products.
4) Modified to get semi synthetic forms.
21. PROTEINS
ALBUMIN
ADVANTAGES
• 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.
22. 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.
USES
• 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.
23. COLLAGEN
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 .
DISADVANTAGES
Chance of antigenic response.
Variability in drug release kinetics.
Poor mechanical strength.
24. SODIUM ALGINATE
• Since the use of organic solvents and high temperature
is not required even viable bacteria and viruses can be
employed.
• It protects the antigens and the vaccines against
degradation in GIT.
• It acts as an adjuvant.
USES
• Alginates are particularly used as carriers of peptides
and other sensitive drug molecules since particulate
carriers can be easily prepared in aqueous solution at
room temperature.
• Alginate micro-spheres are efficiently used for oral
delivery of vaccines.
25. POLYSACCARIDES
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.
• Mol.wt ranges from 1000 to 2,00,000 Daltons
• Enzymes from moulds such as ‘PENCILLIUM’ degrade it.
APPLICATIONS
1) Replacement of Blood loss.
2) Thrombosis Prophylaxis.
3) Improvement of Rheology.
26. 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.