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BIODEGRADABLE POLYMERS

Presented By : Under the Guidance of:

MOHD. IMADUDDIN Mrs. Farhat Fatima (M.Pharmacy) 1STyear/2nd Sem M.pharm (Ph.D)

Dept. of pharmaceutics . Dept. of pharmaceutics.

DECCAN SCHOOL OF PHARMACY Dar-us-salam, Aghapura, Hyderabad- 01. A.P. India

Contents

• Introduction of polymers.• Biodegradable polymers.• Classification of biodegradable polymers.• Polymer Degradation mechanisms

a) Bioerosion mechanism.

b) Enzymatic or chemical degradation.• Synthetic biodegradable polymers.• Natural biodegradable polymers.• Factors affecting biodegradation of polymers.• Applications of biodegradable polymers.• Conclusion.• References.

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INTRODUCTION

• The term "polymer" derives from the ancient Greek word polus, meaning "many, much" and meros, meaning "parts", and refers to a molecule whose structure is composed of multiple repeating units.

• The term was coined in 1833 by Jons Jacob Berzelius.

• A polymer is a large molecule (macromolecules) composed of

many repeated subunits, known as monomers. monomers can

be linked together in various ways to give linear, branched and

cross linked polymers etc…….3

CHARACTERISTICS OF AN IDEAL POLYMER

• Should be versatile and possess a wide range of mechanical, physical, chemical properties.

• Should be non-toxic and have good mechanical strength and should be easily administered.

• Should be inexpensive

• Should be easy to fabricate.

• Should be inert to host tissue and compatible with environment.

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BIODEGRADABLE POLYMERS

• Biodegradable polymers are defined as polymers comprised of monomers linked to one another through functional groups and have unstable links in the backbone.

• They are broken down into biologically acceptable molecules that are metabolized and removed from the body via normal metabolic pathways.

• 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., 5

Classification of biodegradable polymers

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Polymer Degradation

• Polymer degradation is a change in the properties – tensile strength, colour,

shape, etc of a polymer or polymer based product under the influence of

one or more environmental factors such as heat, light or chemicals.

• The term 'biodegradation' is limited to the description of chemical processes

(chemical changes that alter either the molecular weight or solubility of the

polymer)

• ‘Bioerosion' may be restricted to refer to physical processes that result in

weight loss of a polymer device.

• The bioerosion of polymers is basically of two types :-

1) Bulk erosion

2) Surface erosion 7

BIODEGRADATION

ENZYMATIC DEGRADATION COMBINATIONHYDROLYSIS

BULK EROSION SURFACE EROSION

Mechanism Of Biodegradable Polymers

Types of bioerosion

1) Bulk erosion• Degradation takes place

throughout

the whole of the sample. • Ingress of water is faster than the

rate of degradation

Eg : Polylactic acid (PLA)

Polyglycolic acid (PGA)

2) Surface erosion– Sample is eroded from the

surface.– Mass loss is faster than the

ingress of water into the bulk

Eg:Polyanhydrides , polyorthoesters

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ENZYMATIC OR CHEMICAL DEGRADATION

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

CLEAVAGE OF CROSSLINKS

TRANSFORMATION OF SIDE CHAINS

CLEAVAGE OF BACKBONE

Classification of biodegradable polymers based on the source

1) Synthetic biodegradable polymers: eg: Aliphatic poly(esters)

Polyanhydrides

Polyphosphazenes

polyaminoacids

Poly orthoesters etc.,

2) Natural biodegradable polymers: eg: Albumin

Collagen

Dextran

Gelatin

Pectin, starch etc.,11

Synthetic biodegradable polymers

1) Aliphatic poly(esters)• These are prepared by ring opening and polymerization of

cyclic ester.

• Aliphatic polyesters include:

a) POLY (GLYCOLIC ACID)

b) POLY (LACTIC ACID)

c)POLY (CAPROLACTONE)

POLY (GLYCOLIC ACID) ---(--O—C-CH2---)n

POLY (LACTIC ACID) --(--O---C—CH---)n

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a) POLYGLYCOLIC ACID• Polyglycolide or Polyglycolic acid (PGA) is a biodegradable,

thermoplastic polymer and the simplest linear, aliphatic polyester.

• It is a tough fibre-forming polymer. • Due to its hydrolytic instability its use has been limited. • It has a glass transition elevated degree of temperature between 35-40

C., crystallinity, around 45.• Its melting point is in the range 55%, thus resulting in of 225-230 C.

insolubility in water.• polyglycolide is degraded by hydrolysis, and broken down by certain

enzymes.

– Applications

– Used to deliver drugs in the form of microspheres, implants etc.,

– Examples of drugs delivered include steroid hormones, antibiotics, anti cancer

agents etc.,13

b) POLYLACTIC ACID• Polylactic acid or polylactide (PLA) is a thermoplastic aliphatic

polyester derived from renewable resources, such as corn starch, tapioca products (roots, chips or starch) or sugarcane.

• It can biodegrade under certain conditions, such as the presence of oxygen, and is difficult to recycle.

• Highly crystalline, high melting point, low solubility.

• Bacterial fermentation is used to produce lactic acid from corn starch or cane sugar.

APPLICATIONS• PLA is used in the preparation of sutures or orthopaedic devices.

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c) POLYCAPROLACTONE• Polycaprolactone (PCL) is a biodegradable polyester.

• It has a low melting point of around 60 C.

• It has a glass transition temperature of about −60 C.

• slower degradation rate than PLA.

• It remains active as long as a year for drug delivery.

Applications:Drug delivery applications of PCL includes:

- Cyclosporin in the form of nanoparticles

- Ciprofloxacin in the form of dental implants15

2) Poly anhydrides

– Highly reactive and hydrolytically unstable.– Degrade by surface degradation without the need for catalysts.– Aliphatic (CH2 in backbone and side chains) polyanhydrides

degrade within days.– Aromatic (benzene ring as the side chain) polyanhydrides degrade

over several years.– Excellent biocompatibility.– Drug loaded devices prepared by compression molding or

microencapsulation.– Suitable for short term drug delivery.– Used for vaccination and localized tumor therapy.

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3) polyphosphazenes • Its hydrolytic stability/instability is determined by change in side

group attached to macromolecular backbone.

• Used in the construction of soft tissue prosthesis, tissue like coatings, as material for blood vessel prosthesis.

• Used for immobilization of antigen or enzyme.

• Use for drug delivery under investigation

• Based on side chain these are of 3 types:– Hydrophobic phosphazenes– Hydrophilic phosphazenes– Amphiphilic phosphazenes

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4) Polyaminoacids

– Aminoacid side-chains offer sites for drug attachment.– Low-level systemic toxicity owing to their similarity to naturally

occurring amino acids.– Investigated as suture materials.– Artificial skin subtitutes .– Limited applicability as biomaterials due to limited solubility and

processibility .– Drug delivery (difficult to predict drug release rate due to

swelling)– Polymers containing more than three or more amino acids may

trigger antigenic response.– Tyrosine derived polycarbonates developed as high-strength

degradable orthopaedic implants.

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Natural biodegradable polymers

• Natural polymers are an attractive class of biodegradable polymers as they are:– Derived from natural sources– Easily available– Relatively cheap

eg: Albumin

Collagen

Dextran

Gelatin

Pectin,

starch etc.,

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1) Collagen• Collagen is the most widely found protein in mammals and is the

major provider of strength to tissue.• The number of biomedical applications in which collagen have been

utilized is too high; it not only has been explored for use in various types of surgery, cosmetics, and drug delivery, but also in bioprosthetic implants and tissue engineering of multiple organs as well.

• It is used as sutures ,Dressings, etc.

Disadvantages

Poor dimensional stability. Variability in drug release kinetics.

Poor mechanical strength.

Applications:

• Majorly used in ocular drug delivery system

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2) 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.

Applications:

• 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.

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3) 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. Its Mol.wt ranges from 1000 to 2,00,000 Daltons.

Applications:

• Used for colonic delivery of drug in the form of gels.

4) GELATIN• Gelatin is a mixture of peptides and proteins produced by partial hydrolysis

of collagen, extracted from the boiled bones, connective tissues, organs and some intestines of animals. Gelatin is an irreversible hydrolyzed form of collagen, Physicochemical properties depends on the source of collagen, extraction method and thermal degradation.

Applications: Employed as coating material. Gelatin micropellets are used for oral controlled delivery of drugs. 22

FACTORS AFFECTING BIODEGRADATION OF POLYMERS

Morphological 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.

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

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

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.

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REFERENCES• Controlled and Novel Drug Delivery by N. K. Jain; pg no: 27-51.

• Controlled Drug Delivery Concepts and Advances by S.P.Vyas Roop K.Khar; pg no:97-155.

• Design of Controlled Release Drug Delivery System by Xiaoling Li, Bhaskara R. Jasti; pg no:271-303.

• Biodegradable Polymer as drug delivery system; “Synthetic polysaccharides”; edited by-Mark Chasin, Robert Langer Vol- 45; Page No-43-49, 71-90,121-160.

• Advanced Drug Delivery reviews;56(2004);pg no: 1453-1466 by Gesine winzenburg et. al.

 •  N.K. Jain, Pharmaceutical Product Development, second edition : 2011, CVS

Publishers PVT. LTD, New Delhi. Pg.No.701-741.27

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