• Presented to: Dr. Javed AliPresented by: Shakeeb Ahmed

Jamia Hamdard

BIODEGRADABLE POLYMERIC DELIVERY

SYSTEM

BIODEGRADABLE POLYMERS

Nature’s way:

“Every resource made by nature returns to nature”

HO

W LO

NG

DO

ES IT TAK

E?

POLYMERIC MATERIAL DEGRADATION TIME

Cotton rags 1-5 months

Paper 2-5 months

Rope 3-14 months

Orange peels 6 months

Wool socks 1 to 5 years

Cigarette butts 1 to 12 years

Plastic coated paper milk cartons 5 years

Plastic bags 10 to 20 years

Nylon fabric 30 to 40 years

Aluminum cans 80 to 100 years

Plastic 6-pack holder rings 450 years

Glass bottles 1 million years

Plastic bottles May be never

HISTORY

• When polymers were synthesized from glycolic acid in 1920s, at that time, polymer degradation was viewed negatively as a process, where properties and performance deteriorated with time.

BIODEGRADABLE POLYMER: DEFINITION

• “Polymers that degraded/eroded by enzymes introduced in vivo or surrounding living cells or

• Degraded/eroded by non enzymatic process into oligomers ,after their intended purpose to result in natural byproducts (gases : CO2, N2; water, biomass, and inorganic salts)”

• Byproducts are metabolized and removed from the body via normal metabolic pathways.

ADVANTAGES

Less toxic compared to non-biodegradable polymers

Much higher doses of the drug can be delivered locally

Controlled drug release from the formulation

Stabilization of drug

Localized delivery of drug

Decrease in dosing frequency

Reduce side effects

Improved patient compliance

Polymer retain its characteristics till the depletion of drug

BIODEGRADABLE POLYMERS: classification

A: BASED ON ORIGIN Natural origin : Collagen, Albumin, Casein, etc. Semi-synthetic polymers : Gelatin, Dextran , Chitin, Alginate, Chitosan , etc. Synthetic polymers : Aliphatic polyesters : PGA, PLA,PCL, etc. Polyphosphoesters , polyanhydrides , polyphosphazenes, polyaminoacidsB. BASED ON ENVIORNMENTAL FACTORS: Thermosensitive polymer: Polyacrylamide , etc. Electrically and chemically controlled: Poly(pyrrole), collagen, etc. pH sensitive polymer: poly (2-ethylacrylic acid), etc.

C. MISCELLANEOUS: Polymeric phospholipids, Polyethyleneamine, Polyamidoamine, PEG

DIFFERENT MECHANISMS OF DEGRADATION

1. Chemical degradation

2. Physical degradation

3. Enzymatic degradation

ENZYMATIC OR CHEMICAL DEGRADATION

• Chemical or enzymatic degradation–mediated by water, enzymes, microorganisms.

CLEAVAGE OF CROSSLINKS

TRANSFORMATION OF SIDE CHAINS

CLEAVAGE OF BACKBONE

BIODEGRADABLE POLYMERS

• Acetal:

Hemiacetal:

• Ether

• Nitrile

• Phosphonate

• Polycyanocrylate

OH2

+C

O

H H

R' OHO C O

H

H

R R' R OH +

OC

C

C C

C

OH

OH

OH

OH

OH OHC

C

C C

OH

OH

OH

OH

H2O+

C==O

H

H2O

R C O C R'

H H

H H

OH2

R C OH

H

H

R' C OH

H

H

+

R C R

C N

H

R C R

C O

H

NH2

R C R

C O

H

OH

OH2 OH2

RO P OR'

O

OR''

OH P OH

O

OR''

OH2

+ +R OH OH R'

R C C C C R'

CN

C

OR''

CNH

HO C

OR'''

O

H

H

OH2R C C C

CN

C

OR''

H

HO

H

H

OH C R'

CN

C

OR'''

O

+

1) Bulk erosion

• Degradation takes place throughout

the whole of the sample.

• Water intake is faster than the polymerchain scission

• Eg : polyesters, PLA, PLGA, polylactones, poly(amino acids), and polyphosphazenes

2) Surface erosion

– Sample is eroded from the surface.

– polymer degradation is much faster

than water intake

– E.g. Polyanhydrides, polyorthoesters11

PHYSICAL DEGRADATION

METHODS OF STUDYING POLYMER DEGRADATION

• Morphological changes (swelling, deformation, bubbling, disappearance)

• Weight loss

• Thermal behavior changes (DSC)

• Molecular weight changes

– Size exclusion chromatography

– Gel permeation chromatography

– Mass spectroscopy

• Change in chemistry (IR, NMR)

MOLDING (Formation of drug polymer matrix)

Methods:1. Compression molding2. Melt molding3. Solvent casting

1.Compression molding

• Polymer and drug particles are milled to a particle size range of 90-150 µm

• Drug/polymer mix is compressed at approx. 30,000 psi• Formation of some types of tablet/matrix

MELT MOLDING

SOLVENT CASTING

APPLICATIONS OF BIODEGRADABLE POLYMERS

• Polymer system for gene therapy.

• Biodegradable polymer for ocular, tissue engineering, vascular,orthopedic, skin adhesive & surgical glues.

• Biodegradable drug delivery system for therapeutic agents such asanti-tumor, antipsychotic agent, anti-inflammatory agent.

• Polymeric materials are used in and on soil to improve aeration,and promote plant growth and health.

• Many biomaterials, especially heart valve replacements and bloodvessels, are made of polymers like Dacron, Teflon and polyurethane.

•

•

APPLICATION

APPLICATION

APPLICATION: as a Drug Delivery System

APPLICATION: as an ocusert

BIODEGRADABLE POLYMERS: Application in drug delivery

BIODEGRADABLE POLYMERS: Application in drug delivery

BIODEGRADABLE POLYMERS: Application in drug delivery

INDIVIDUAL APPLICATION OF BIODEGRADABLE POLYMERSPOLYMERS APPLICATION

Collagen In wound repairing

Chitosan Gelling agent

Dextran Plasma volume expander

Lectins As a mucoadhesive

Cyclodextrins, guar gum, pectin, insulin

Delivery of drug to colon

Poly -€-caprolactone Microspheres, implants

Rosin As an adhesive in TDDS

INDIVIDUAL APPLICATION OF BIODEGRADABLE POLYMERS

POLYMERS APPLICATION

PLA, PLGA

• Excipients for injectable drugs • PLA + Doxycycline…….periodontal disease• PLGA + Growth hormone…Growth

deficiency• PLA + Leuprolide acetate….Prostate

cancer

CONCLUSION

• Numerous synthetic biodegradable polymers are available and stillbeing developed for sustained and targeted drug delivery applications.

• Biodegradable polymers have proven their potential for thedevelopment of new, advanced and efficient DDS and capable ofdelivering a wide range of bioactive materials.

• However, only few have entered the market since many drugs faces theproblem of sensitivity to heat, shear forces and interaction betweenpolymers.

• These problems can be overcome by fully understanding thedegradation mechanism to adjust the release profile.

REFERENCES

• Kumari A, Yadav SK, Yadav SC (2010); “Biodegradable polymeric nanoparticles based drug delivery systems”; Colloids Surf B Biointerfaces