•BIODEGRADABLE POLYMERS BIODEGRADABLE POLYMERS AND NATURAL POLYMERSAND NATURAL POLYMERS

PRESENTED BY PRESENTED BY SHIVA KUMAR YSHIVA KUMAR Y M.PHARMACY 1M.PHARMACY 1STST yr yr K.L.E UNIVERSITY.BelgaumK.L.E UNIVERSITY.Belgaum

DEFINITIONDEFINITIONBIODEGRADABLE POLYMERSBIODEGRADABLE POLYMERSMECHANISM OF BIODEGRADATIONMECHANISM OF BIODEGRADATIONNATURAL POLYMERSNATURAL POLYMERSCONCLUSIONCONCLUSIONREFERENCESREFERENCES

CONTENTSCONTENTS

POLYMER DEFINITIONPOLYMER DEFINITION

Polymers are long chain organic molecules and are assembled from many smaller molecules called monomers They mostly contain elements like C,H,O,N,P etc,.

1)Schematic Illustration Of Control Drug Release,2) Single dose 1)Schematic Illustration Of Control Drug Release,2) Single dose administrationadministration

Biodegradable polymersBiodegradable polymers

These are the These are the PolymersPolymers which Degrade which Degrade slowly and get slowly and get expelled expelled out of the out of the bodybody

after fulfilling its action i.e., after fulfilling its action i.e., Drug Drug releaserelease..

The most imp mechanism for The most imp mechanism for degradationdegradation

is chemical reaction – i.e. Hydrolysis.is chemical reaction – i.e. Hydrolysis.

BIODEGRADATIONBIODEGRADATION

ENZYMATIC DEGRADATION COMBINATIONHYDROLYSIS

BULK EROSION SURFACE EROSION

MECHANISM OF BIODEGRADABLE POLYMERS

TYPE 1A

TYPE 1B

A A A B B B

A B represents hydrolysis,ionisation or protonation

TYPE 2

TYPE 3

HIGH Mol.wt LOW Mol.wt

Factors Influencing Factors Influencing BiodegradationBiodegradation

:: CHEMICAL STRUCTURECHEMICAL STRUCTURE

(a) Functional Group(a) Functional Group

(b) Hydrophobicity(b) Hydrophobicity

MORPHOLOGYMORPHOLOGY

(a) Crosslink density(a) Crosslink density

PARTICLE SIZEPARTICLE SIZE

Pre Requisites of B-D-Pre Requisites of B-D-PolymersPolymers BIO COMPATABILITYBIO COMPATABILITY MECHANICAL STRENGTHMECHANICAL STRENGTH STABILITYSTABILITY BIO RESORBIBILITYBIO RESORBIBILITY INERTINERT

Biodegradation : Biodegradation : It is the process of chain It is the process of chain cleavage, cleavage,

Found out by change in Mol.wt.Found out by change in Mol.wt.

Bioerosion : Bioerosion : It is the sum of all process, leading to It is the sum of all process, leading to lossloss

Of mass from a polymer matrix.Of mass from a polymer matrix.

NoteNote : Hydrophobic polymers have to undergo : Hydrophobic polymers have to undergo degradation before Erosion takes place.degradation before Erosion takes place.

TYPES OF BIODEGRADABLE TYPES OF BIODEGRADABLE POLYMERSPOLYMERS

POLY ESTERSPOLY ESTERS

POLY PHOSPHO ESTERSPOLY PHOSPHO ESTERS

POLY ANHYDRIDESPOLY ANHYDRIDES

POLY OLEFINSPOLY OLEFINS

POLY AMIDESPOLY AMIDES

POLY (GLYCOLIC ACID) ---(--O—C-CHPOLY (GLYCOLIC ACID) ---(--O—C-CH22---)---)nn

POLY (LACTIC ACID) --(--O---C—CH---)POLY (LACTIC ACID) --(--O---C—CH---)nn

POLY (CAPROLACTONE) --(--O—C---(CHPOLY (CAPROLACTONE) --(--O—C---(CH22))55---)---)nn

First polymers used in medicine dated back to First polymers used in medicine dated back to 19541954..

Most Most commercialised commercialised class of Polymers class of Polymers

ex : ADRIAMYCINex : ADRIAMYCIN®®

Bio compatible & Bio resorbableBio compatible & Bio resorbable Synthesis & Co polymerisation can be easily doneSynthesis & Co polymerisation can be easily done t t ½ ½ ranges from weeks (PLA) to years (PCL).ranges from weeks (PLA) to years (PCL).

APPLICATIONS : APPLICATIONS : (1)(1) Sutures, ligatures etc.Sutures, ligatures etc. (2) DECAPEPTYL (2) DECAPEPTYL ® ® , LUPRON DEPOT , LUPRON DEPOT ®®

o

CH3

o

o

POLY ESTERS

Poly (lactide) rods implanted into Rabbits

(9 weeks) (16 weeks)(9 weeks) (16 weeks)Degradation is mainly by : (1) ENZYMATIC (2) HYDROLYTIC (3) MICROBIAL ex : Esterase, pronase, bromelain

HYDROLYSIS :R—COO---R1 + H2O R—COOH + R1 –OH

MICROBIAL DEGRADATION :Fungi – ‘ FUSARIUM MONILIFORMAE’ YEAST- ‘CRYPTOCOCCUS’

POLY PHOSPHO ESTERSPOLY PHOSPHO ESTERS OO --(--P---O---R---O--)-- Poly (Phosphate ) --(--P---O---R---O--)-- Poly (Phosphate )

OROR11

OO --(--P---O---R---O--)-- Poly (Phosphonate)--(--P---O---R---O--)-- Poly (Phosphonate)

RR11

Highly Adjustable propertiesHighly Adjustable properties Good BiocompatabiltyGood Biocompatabilty High DegradabilityHigh Degradability High Mol.wt gives good strengthHigh Mol.wt gives good strength

Get Degraded within 6 monthsGet Degraded within 6 months tt1/21/2 is from 2 to 4 months is from 2 to 4 months Degradation products – phosphates & Degradation products – phosphates &

alcoholalcohol

APPLICATIONS : APPLICATIONS : Paclitaxel, cisplatinPaclitaxel, cisplatin Plasmid DNA, IL-2Plasmid DNA, IL-2

STERILISATION & STABILITY :STERILISATION & STABILITY : Highly Susceptible to Hydrolysis in Open AirHighly Susceptible to Hydrolysis in Open Air Should be stored in a DessicatorShould be stored in a Dessicator Sterilisation Only by Gamma IrradiationSterilisation Only by Gamma Irradiation

DRUG RELEASEDRUG RELEASE ::

POLY ANHYDRIDESPOLY ANHYDRIDES

HO--[---(C—RHO--[---(C—R11----C)----C)n1n1-----O-----(C---R-----O-----(C---R22---C-)---C-)n2n2--]--]n3n3---OH---OH

GENERAL STRUCTUREGENERAL STRUCTURE

Two Two carboxylic groupscarboxylic groups at each end at each end High Degradation rateHigh Degradation rate Degrade by Degrade by Surface ErosionSurface Erosion Aromatic P.A’s are slower degradingAromatic P.A’s are slower degrading CopolymerisationCopolymerisation can control degradation rate can control degradation rate Biological tests in Rabbits proved them Non-mutagenicBiological tests in Rabbits proved them Non-mutagenic

APPLICATIONSAPPLICATIONS : : 1) PEPTIDES FOR OSTEOMYLITES1) PEPTIDES FOR OSTEOMYLITES

2) PROTIENS FOR BRAIN TUMOUR2) PROTIENS FOR BRAIN TUMOUR

DRUG RELEASEDRUG RELEASE : :

Mostly they degrade by Mostly they degrade by Surface ErosionSurface Erosion (S.E) (S.E) Their tTheir t1/21/2 is less than 30 days is less than 30 days

Due to S.E. proportion of drug releasedDue to S.E. proportion of drug released

alters with alters with timetime

DRUG STABILITY :DRUG STABILITY : Primary aminePrimary amine containing drugs react at pH containing drugs react at pH

7.27.2 The above reaction is not seen below pH 5.0The above reaction is not seen below pH 5.0 They are ideal when action is required for They are ideal when action is required for 1 1

weekweek They have more application as They have more application as parentrals.parentrals.

POLY OLEFINSPOLY OLEFINSPROPERTIES :PROPERTIES : Carbon Chain based PolymersCarbon Chain based Polymers They contain Double & Triple bonds extensivelyThey contain Double & Triple bonds extensively Presence of substituents like Cyanoacryl groups Presence of substituents like Cyanoacryl groups

enhance Degradation rateenhance Degradation rate An Example for rapidly oxidized olefin isAn Example for rapidly oxidized olefin is

Poly propylene Poly propylene Introduction of vinyl group makes them more Introduction of vinyl group makes them more

stablestable

ex : Teflonex : Teflon

APPLICATIONS : APPLICATIONS : 1) SUTURES,CATHETERS,IMPLANTS 1) SUTURES,CATHETERS,IMPLANTS

2) MEMBRANE BARRIER FOR DRUGS2) MEMBRANE BARRIER FOR DRUGS

POLY AMIDESPOLY AMIDES

PROPERTIES :PROPERTIES : These Are Generally Called As ‘These Are Generally Called As ‘NYLONSNYLONS’.’. They Are Generally Slowly DegradingThey Are Generally Slowly Degrading BY INTRODUCTION of COPOLYMERS likeBY INTRODUCTION of COPOLYMERS like

‘ ‘L-Aspartic AcidL-Aspartic Acid', Nearly 40% of Polymer Is ', Nearly 40% of Polymer Is

Degraded within 1 week.Degraded within 1 week. Mainly degraded In vivo by Non-specific Mainly degraded In vivo by Non-specific

‘Amidases’‘Amidases’ They are more stable when compared to otherThey are more stable when compared to other

PolymersPolymers

APPLICATIONS :APPLICATIONS : Haemofiltration Membranes, Haemofiltration Membranes,

Dressings, sutures etc. Dressings, sutures etc.

ADVANTAGES :ADVANTAGES :

Play an essential role in Formulation of Play an essential role in Formulation of CDDSCDDS

Patient compliance is improvedPatient compliance is improved Bio compatibleBio compatible Help in adjusting duration of action of Help in adjusting duration of action of

DrugDrug Most of them are InertMost of them are Inert Copolymerisation can be doneCopolymerisation can be done

DISADVANTAGES :DISADVANTAGES : Most of them are ExpensiveMost of them are Expensive Drug release cannot be 100% predictedDrug release cannot be 100% predicted

NATURAL POLYMERSNATURAL POLYMERS These are the polymers obtained from naturalThese are the polymers obtained from natural

Resources, and are generally Non-toxic.Resources, and are generally Non-toxic.

NATURAL POLYMERS

PROTEINS Polysaccharides Nucleic Acids

Ex: COLLAGEN ALBUMIN FIBRIN

Ex : DEXTRAN CHITOSAN STARCH

Ex : DNA RNA

ADVANTAGES : 1) Readily & Abundantly Available 2) Comparatively Inexpensive 3) Non toxic products 4) Modified to get semi synthetic forms

PROTEINSPROTEINS

COLLAGEN:COLLAGEN:It is a major structural protein in animals It is a major structural protein in animals It is used as sutures ,Dressings, etc.It is used as sutures ,Dressings, etc.Readily isolated &purified in large quantites.Readily isolated &purified in large quantites.Can be processed in variety of forms .Can be processed in variety of forms .DISADVANTAGES:DISADVANTAGES:Chance of antigenic response.Chance of antigenic response.Variability in drug release kinetics.Variability in drug release kinetics.Poor mechanical strength.Poor mechanical strength.

FIBRINOGEN :FIBRINOGEN : Soluble Plasma protein (M.W. 3,40.000)Soluble Plasma protein (M.W. 3,40.000) It is commonly used as CoagulantIt is commonly used as Coagulant Useful in preparation of Micro spheres of Anti Useful in preparation of Micro spheres of Anti

cancer agentscancer agents

DISADVANTAGES :DISADVANTAGES : ANTIGENICITYANTIGENICITY INTERACTION WITH DRUGINTERACTION WITH DRUG IMPROPER DRUG RELEASEIMPROPER DRUG RELEASE LESS SHELF LIFELESS SHELF LIFE

PolysaccaridesPolysaccaridesDEXTRAN :DEXTRAN : DextranDextran is a complex branched is a complex branched polysaccharidepolysaccharide

made of many made of many glucoseglucose molecules joined into chains molecules joined into chains of varying lengths of varying lengths

It consists of α-D-1,6-glucose-linked glucan with It consists of α-D-1,6-glucose-linked glucan with side-chains linked to the backbone of Polymerside-chains linked to the backbone of Polymer

Mol.wt ranges from 1000 to 2,00,000 DaltonsMol.wt ranges from 1000 to 2,00,000 Daltons Enzymes from moulds such as ‘PENCILLIUM’ degrade Enzymes from moulds such as ‘PENCILLIUM’ degrade

it.it.

APPLICATIONSAPPLICATIONS – 1) Replacement of Blood loss– 1) Replacement of Blood loss

2) Thrombosis Prophylaxis2) Thrombosis Prophylaxis

3) Improvement of Rheology3) Improvement of Rheology

CHITOSAN :CHITOSAN : It consists of B-1-4 linked 2 amino-2-deoxy gluco -It consists of B-1-4 linked 2 amino-2-deoxy gluco - pyranose moietiespyranose moieties Commercially manufactured by N-deacetylation ofCommercially manufactured by N-deacetylation of Chitin which is obtained from Mollusc shellsChitin which is obtained from Mollusc shells It is soluble only in acidic pH i.e. when amino It is soluble only in acidic pH i.e. when amino group is protonated.group is protonated. Thereby it readily adheres to bio membranes.Thereby it readily adheres to bio membranes. It is degraded mainly by Glycosidases & lysozymes.It is degraded mainly by Glycosidases & lysozymes.

ADVANTAGES :ADVANTAGES : Free availability, Biocompatibility, BiodegradabilityFree availability, Biocompatibility, Biodegradability Bioadhesive, unique properties.Bioadhesive, unique properties.

conclusionconclusion PolymersPolymers play an essential role in the play an essential role in the

Development of Development of CDDSCDDSThe potential of The potential of CopolymerisationCopolymerisation

shouldshould

be deeply understood & applied.be deeply understood & applied.NewNew Biodegradable polymers should be Biodegradable polymers should be

InvestigatedInvestigatedNatural polymersNatural polymers should not be under- should not be under-

Estimated as they have high potentialEstimated as they have high potential

And readily AvailableAnd readily Available

REFERENCES:REFERENCES:

• S.P.VYAS AND R.K.KHAR ,CONTROLLED S.P.VYAS AND R.K.KHAR ,CONTROLLED DRUGE DELIVERY CONCEPT AND DRUGE DELIVERY CONCEPT AND ADVANCES,FIRST EDITION 2002.ADVANCES,FIRST EDITION 2002.

• CONTROLLED DRUG DELIVERY SYSTEM BY CONTROLLED DRUG DELIVERY SYSTEM BY STEPHEN D.BRUCK.STEPHEN D.BRUCK.

• CONTROLLED AND NOVEL DELIVERY CONTROLLED AND NOVEL DELIVERY SYSTEM N.K.JAINSYSTEM N.K.JAIN

• INDIAN DRUGS .VOL-39;2002INDIAN DRUGS .VOL-39;2002• INDIAN DRUGS.VOL-30;1993.INDIAN DRUGS.VOL-30;1993.• www.google.comwww.google.com

•THANK YOUTHANK YOU