Recent Updates in Syn. Polymers

8/9/2019 Recent Updates in Syn. Polymers

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Recent updates in syntheticRecent updates in syntheticpolymers used in drugpolymers used in drugdelivery systemsdelivery systems

KUSUM SINGHKUSUM SINGH

NEELAM SINGHNEELAM SINGH


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CONTENTSCONTENTS

INTRODUCTIONINTRODUCTION

DEFINITIONDEFINITION

CLASSIFICATIONCLASSIFICATION

PROPERTIES & SELECTION OF SYNTHETICPROPERTIES & SELECTION OF SYNTHETICPOLYMERSPOLYMERS

SYNTHETIC POLYMERS USED IN DRUG DELIVERYSYNTHETIC POLYMERS USED IN DRUG DELIVERY

SYSTEMSSYSTEMS22


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INTRODUCTIONINTRODUCTION

Significant advances have been made in development ofSignificant advances have been made in development ofvarious drug delivery devices with the help of polymers.various drug delivery devices with the help of polymers.

The earliest DDS first introduced in 1970s were based onThe earliest DDS first introduced in 1970s were based onpolymers formed from lactic acid.polymers formed from lactic acid.

Today polymeric materials still provides most importantToday polymeric materials still provides most important

avenues of research primarily because of ease ofavenues of research primarily because of ease ofprocessing & ability of researchers to readily control theirprocessing & ability of researchers to readily control theirchemical & physical properties via. Molecular system.chemical & physical properties via. Molecular system.

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DEFINITIONDEFINITION

POLYMERSPOLYMERS::--

Compounds with high molecular masses formed byCompounds with high molecular masses formed bycombination of large number of simple molecules called ascombination of large number of simple molecules called asmonomers.monomers.

Prepared by addition / condensation polymerization.Prepared by addition / condensation polymerization.

In GreekIn Greek,, PolyPolymeans many &means many &merosmeros means units/parts.means units/parts.

Polymers are of 3 types:Polymers are of 3 types:--

Natural, Semisynthetic, Synthetic.Natural, Semisynthetic, Synthetic.

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CLASSIFICATION OF SYNTHETIC POLYMERSCLASSIFICATION OF SYNTHETIC POLYMERS

ON THE BASIS OF

STRUCTURE

BRANCHED CHAIN

POLYMERS

EXAMPLES:-

Low Density Polythene

CROSS LINKED

POLYMERSEXAMPLES:-

Bakelite,

MF Resin

LINEAR POYMERS

EXAMPLES:-

PEG, Polyesters

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CONTDCONTD

ON THE BASIS OFDEGRADABILITY OF POLYMERS

BIODEGRADABLEPOLYMERS

NONBIODEGRADABLEPOLYMERS

ENVIRONMENTRESPONSIVE

POLYMERS

ELECTRICALLY &

CHEMICALLY

CONTROLLED

POLYMERS

THERMOSENSITIVE

POLYMERS

pH-SENSITIVE

POLYMERS

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CLASSCLASS EXAMPLESEXAMPLES

A)A) BIODEGRADABLE POLYMERSBIODEGRADABLE POLYMERS

POLYESTERSPOLYESTERS

POLYANHYDRIDESPOLYANHYDRIDES

POLYAMIDEPOLYAMIDE

PHOSPHOROUSBASEDPHOSPHOROUSBASED

OTHERSOTHERS

PLA, PGA, PHBPLA, PGA, PHB

PCL, PMA, POLYDIOXANONESPCL, PMA, POLYDIOXANONES

POLYSEBACICACID, PTAPOLYSEBACICACID, PTA

POLYPHOSPHAZENES,POLYPHOSPHAZENES,

POLYPHOSPHONATEPOLYPHOSPHONATEPOLYCYANOACRYLATES,POLYCYANOACRYLATES,POLYURETHENES, POLYORTHOESTERSPOLYURETHENES, POLYORTHOESTERS

B)B) NONBIODEGRADABLENONBIODEGRADABLE

CELLULOSE DERIVATIVE

SILICONES

ACRYLICPOLYMERS

OTHERS

CMC, EC, CA, CAPCMC, EC, CA, CAP

PDS, COLLOIDALSILICAPDS, COLLOIDALSILICA

PMA, PMMA, PHEMAPMA, PMMA, PHEMA

PVP, EVA. POLYOXAMERPVP, EVA. POLYOXAMER

SYNTHETIC POLYMERSYNTHETIC POLYMER :-

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ON THE BASIS OF

MONOMERIC UNITS

CONTDCONTD

HOMOPOLYMERS COPOLYMERS

GRAFTED

COPOLYMERS

ALTERNATING

COPOLYMERS

BLOCK

COPOLYMERSRANDOM

COPOLYMERS

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PROPERTIES & SELECTION OFPROPERTIES & SELECTION OF

POLYMERSPOLYMERS

POLYMER ISCHOOSENONBASISOFPOLYMER ISCHOOSENONBASISOF ::--

Physicochemical propertiesPhysicochemical properties

Need for biochemical characterization.Need for biochemical characterization.

Chemical compositionChemical composition

Micro structural designMicro structural design

Surface properties like lubricity, hydrophilicity, smoothness,Surface properties like lubricity, hydrophilicity, smoothness,surface energysurface energy

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PROPERTIESOF SYNTHETIC POLYMER THAT NEEDPROPERTIESOF SYNTHETIC POLYMER THAT NEED

TO BE CONSIDERD FOR APPLICATION OF POLYMERSTO BE CONSIDERD FOR APPLICATION OF POLYMERS

TODRUG DELIVERY SYSTEMSTODRUG DELIVERY SYSTEMS

SolubilitySolubility

ViscosityViscosity

PolymerPolymer-- Solvent interactionSolvent interaction

CrystallinityCrystallinity

Polymer dissolutionPolymer dissolution

Bioadhesivity ofHydrophilic polymerBioadhesivity ofHydrophilic polymer

Polymer erosion &BiodegradationPolymer erosion &Biodegradation1010


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SYNTHETIC POLYMERS USED IN DRUGSYNTHETIC POLYMERS USED IN DRUG

DELIVERYDELIVERY SYSTEMSSYSTEMS

SYNTHETICPOLYMERS IN DENDRITICSYNTHETICPOLYMERS IN DENDRITIC

DRUG DELIVERYSYSTEMSDRUG DELIVERYSYSTEMS

DENDRIMERSDENDRIMERS--

Transport extremely highTransport extremely high

densities of drug molecules.densities of drug molecules.

It is suitable carrier system because:It is suitable carrier system because:--

Their size & structure can be controlled.Their size & structure can be controlled.

Encapsulate small drug molecule to form Polymer micelles.Encapsulate small drug molecule to form Polymer micelles.

Serves as hubs onto which large number of drug molecules canServes as hubs onto which large number of drug molecules can

attached via covalent bond.attached via covalent bond.1111


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PAMAM DendrimerPAMAM Dendrimer Used in gene delivery. It has amineUsed in gene delivery. It has amineTerminal group which binds to DNA by electrostatic charge.Terminal group which binds to DNA by electrostatic charge.

Prepared either as Divergent /Convergent type.Prepared either as Divergent /Convergent type.StarburstStarburstTMTM PAMAM dendrimer in intactPAMAM dendrimer in intact (Polyfect(Polyfect(R)(R))) &&fractured formfractured form (Superfect(Superfect).).

Fractured form shows better gene expression.Fractured form shows better gene expression.

Polyethyleneimine(PEI)Polyethyleneimine(PEI)--

To prepare PEITo prepare PEI-- gene complex.gene complex. After internalization release of gene complex by endosome occurs due toAfter internalization release of gene complex by endosome occurs due to

protonation of internal 3protonation of internal 3 Nitrogen by endosomal protonsNitrogen by endosomal protonswhich then results in swelling of endosome & ultimatelywhich then results in swelling of endosome & ultimatelyreleases DNA.releases DNA.

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SYNTHETICPOLYMERSYNTHETICPOLYMER APPLICABILITYAPPLICABILITY

Poly Amino Amine dendrimerPoly Amino Amine dendrimer To deliver 5To deliver 5--Fluro uracil.Fluro uracil.

For occular drug delivery ofFor occular drug delivery ofPilocarpine Nitrate.Pilocarpine Nitrate.

Increases solubility ofNifedipineIncreases solubility ofNifedipine

Poly aryl ether dendrimerPoly aryl ether dendrimer To deliver MethotrexateTo deliver Methotrexate

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SYNTHETIC POLYMER USED IN MUCOADHESIVESYNTHETIC POLYMER USED IN MUCOADHESIVE

BUCCAL DRUG DELIVERY SYSTEMSBUCCAL DRUG DELIVERY SYSTEMS

Factors to be consideredFactors to be considered ::-- Chain flexibilityChain flexibility

Low molecular weightLow molecular weight

Ability to form HAbility to form H--bondingbonding

Concentration & swelling of polymers.Concentration & swelling of polymers.

Synthetic Polymers used as Permeation enhancersSynthetic Polymers used as Permeation enhancers::--

CLASSCLASS SYNTHETICPOLYMERSSYNTHETICPOLYMERS

SURFACTANTS Polyoxyethylene, PolyoxyethylenePolyoxyethylene, Polyoxyethylene--99--lauryllaurylether,Polyoxyethyleneether,Polyoxyethylene--2020--cetyl ethercetyl ether

THIOLATEDTHIOLATEDPOLYMERSPOLYMERS

Polycarbophil, Polyacrylic acidPolycarbophil, Polyacrylic acid

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BIOADHESIVEBIOADHESIVE PROPERTIESPROPERTIES CHARACTERISTICSCHARACTERISTICS

PolyPoly--hydroxylhydroxyl

ButyrateButyrate

Poly(ePoly(e--caprolactone)caprolactone)

PolyorthoestersPolyorthoesters

PolyphosphazenesPolyphosphazenes

PolycyanoacrylatesPolycyanoacrylates

Polyvinyl AcetatePolyvinyl Acetate

PolyethyleneoxidePolyethyleneoxide--bb--propylene oxidepropylene oxide

BiodegradableBiodegradable

Properties can be changedProperties can be changedby chemical modificationby chemical modification

Surface eroding polymerSurface eroding polymer

Can be tailored withCan be tailored withversatile side chainversatile side chainfunctioningfunctioning

BiodegradableBiodegradable

BiocompatibleBiocompatible

Amphiphillic surfactantAmphiphillic surfactant

BiocompatibleBiocompatible

Matrix for DDSMatrix for DDS

Cell encapsulationCell encapsulation

Sustained DDS,Sustained DDS,opthalmologyopthalmology

To make films, HydrogelsTo make films, Hydrogelsin DDSin DDS

Surgical adhesives, gluesSurgical adhesives, gluesin DDSin DDS

Gels &BlendedGels &Blendedmembranes in DD &membranes in DD &ImmobilizationImmobilization

Protein deliveryProtein delivery

BIOADHESIVE POLYMERS IN MUCOADHESIVEBIOADHESIVE POLYMERS IN MUCOADHESIVE

DRUG DELIVERY SYSTEMSDRUG DELIVERY SYSTEMS

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SYNTHETIC POLYMERS USED IN SUSTAINEDSYNTHETIC POLYMERS USED IN SUSTAINED

RELEASE DRUG DELIVERY SYSTEMSRELEASE DRUG DELIVERY SYSTEMS

Sustained Release DDS follows 1Sustained Release DDS follows 1stst order release kinetics.order release kinetics.

Increased crosslinking of polymers decreases diffusion rate & thusIncreased crosslinking of polymers decreases diffusion rate & thusimproves sustained release properties of polymers & decreasesimproves sustained release properties of polymers & decreasesmucoadhesivity.mucoadhesivity.

Synthetic Absorbable PolymersSynthetic Absorbable Polymers-- includeinclude homopolymers like PLA,homopolymers like PLA,PGA, PCL, Polytrimethylene carbonate, Poly(pPGA, PCL, Polytrimethylene carbonate, Poly(p--dioxanone) &dioxanone) &copolymers likecopolymers like-- Poly lactidePoly lactide--coco--glycolide, Poly (glycolideglycolide, Poly (glycolide--coco--trimethylene carbonate).trimethylene carbonate).

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Poly(Monosteroyl GlycerolPoly(Monosteroyl Glycerol--coco--succinate)succinate)

For Sustained release ofFor Sustained release ofTheophylline/ Risperidone fromTheophylline/ Risperidone frommicroparticles inmicroparticles in--vitrovitro

Polyvinyl AcetatePolyvinyl Acetate For sustained release capsules ofFor sustained release capsules ofNifedipineNifedipine

Eudragit RLPM, RSPM &HPMCEudragit RLPM, RSPM &HPMC Sustained release of theophyllineSustained release of theophylline

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SYNTHETIC POLYMERS USED IN OPTHALAMICDRUGSYNTHETIC POLYMERS USED IN OPTHALAMICDRUG

DELIVERY SYSTEMSDELIVERY SYSTEMS

Properties of synthetic Polymers considered for Opthalamic DDSProperties of synthetic Polymers considered for Opthalamic DDS--

NonNon--Toxic, Biodegradable, Biocompatible, Optically transparent, Do notToxic, Biodegradable, Biocompatible, Optically transparent, Do notimpede vision, Tolerable, good retention properties, mucoadhesivity.impede vision, Tolerable, good retention properties, mucoadhesivity.

NonNon--Biodegradable polymeric bioadhesives used as drug deliveryBiodegradable polymeric bioadhesives used as drug deliverysystems:systems:--

Copolymers based on Vinylpyrrolidone, Methacrylic acid,Copolymers based on Vinylpyrrolidone, Methacrylic acid,PolydimethylenePolydimethylene-- siloxane, Poly (Nsiloxane, Poly (N--isopropyl acrylamide), PAMAMisopropyl acrylamide), PAMAMdendrimers.dendrimers.

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SYNTHETICPOLYMERSSYNTHETICPOLYMERS APPLICABILITYAPPLICABILITY

Polyhydroxy ethylPolyhydroxy ethyl --methacrylatemethacrylate

Used to formulate liposomes loaded withUsed to formulate liposomes loaded withDimyristoylDimyristoyl phosphatidylcholinephosphatidylcholine (DMPC). It(DMPC). Itis optically transparent & release drug for ais optically transparent & release drug for aperiod of8 days.period of8 days.

Poly (D,LPoly (D,L--lactide)lactide) Biodegradable polymer used for sustainedBiodegradable polymer used for sustainedretinal delivery ofCelecoxib to inhibitretinal delivery ofCelecoxib to inhibitdiabetes induced Retinal oxidative demagediabetes induced Retinal oxidative demage

Polyanhydrides, PolyorthoestersPolyanhydrides, Polyorthoesters For sustained release of5For sustained release of5--FUFU

Poly (Poly (--caprolactone) rodcaprolactone) rodshaped implantsshaped implants

Tolerated by retinal tissues & used toTolerated by retinal tissues & used torelease corticosteroidrelease corticosteroid triamcinolonetriamcinolone acetideacetideover 4 weeksover 4 weeks

CONTDCONTD

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SYNTHETC POLYMERS USED IN TRANSDERMALSYNTHETC POLYMERS USED IN TRANSDERMAL

DRUG DELIVERY SYSTEMDRUG DELIVERY SYSTEM

Polymers are the backbone of TDDS.Polymers are the backbone of TDDS.

TDDS are fabricated as multilayered polymeric laminates or drugTDDS are fabricated as multilayered polymeric laminates or drug--polymer matrix is sandwiched between two polymeric layers i.e.polymer matrix is sandwiched between two polymeric layers i.e.backing layer & inner polymeric layer which act as adhesive &backing layer & inner polymeric layer which act as adhesive &RateRate-- controlling membrane.controlling membrane.

TDDS is formulated either as Matrix form / Reservoir form.TDDS is formulated either as Matrix form / Reservoir form.

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IN TDDS POLYMERS ACTS AS

MATRIX FORMERSBACKING LAYERS

RELEASE LINERS

RATE CONTROLING

MEMBRANE PRESSURE- SENSITIVE

ADHESIVES (PSAs)2424


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c)c) PolyvinylpyrrolidonePolyvinylpyrrolidone

Matrix formers with 30% Dibutyl Phthalate to deliver DiltiazemMatrix formers with 30% Dibutyl Phthalate to deliver Diltiazem

Hydrochloride & DomethacinHydrochloride & Domethacin

d)d) HPMCHPMC

Hydrophillic, swellable polymer used for Oral Controlled DDSHydrophillic, swellable polymer used for Oral Controlled DDS

Matrix formers in Propranolol HClMatrix formers in Propranolol HCl

For fast release of drug.For fast release of drug.

2)2) RATE CONTROLLING MEMBRANERATE CONTROLLING MEMBRANE

a)a) Ethyl Vinyl AcetateEthyl Vinyl Acetate

By altering Vinyl Acetate content membrane permeability can be controlledBy altering Vinyl Acetate content membrane permeability can be controlled

b)b) Silicone RubberSilicone Rubber BiocompatibleBiocompatible

Highly permeable to steroidsHighly permeable to steroids

Ease of fabricationEase of fabrication

Low microscopic viscosity & used in Controlled Release devices.Low microscopic viscosity & used in Controlled Release devices.

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c) Poly Urethanec) Poly Urethane

Rubbery & increased permeabilityRubbery & increased permeability

Two types:Two types:-- Polyether urethanes & Polyester UrethanesPolyether urethanes & Polyester Urethanes

Due to more Biodegradability Polyester Urethanes are moreDue to more Biodegradability Polyester Urethanes are more

preffered. It is used for Hydrophillic polar drugs.preffered. It is used for Hydrophillic polar drugs.

3)3) PRESSURE SENSITIVE ADHESIVESPRESSURE SENSITIVE ADHESIVES

Characteristic of viscoCharacteristic of visco-- elastic materialelastic material

a)a) Poly Iso ButylenePoly Iso Butylene Formed by cationic polymersFormed by cationic polymers

b)b) Poly AcrylatesPoly Acrylates

Amorphous, gives water clear color in solution & stable towardsAmorphous, gives water clear color in solution & stable towards

ageing & have good mechanical properties.ageing & have good mechanical properties.

c)c) SiliconesSilicones

Contains low viscosity Dimethyl siloxane polymer.Contains low viscosity Dimethyl siloxane polymer.

Silicate Resin + PDMS undergoes condensation to form Silicone PSASilicate Resin + PDMS undergoes condensation to form Silicone PSA2727


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4)4) BACKING MATERIALSBACKING MATERIALS

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SYNTHETIC POLYMERS USED INSYNTHETIC POLYMERS USED INHYDROGEL DRUG DELIVERYHYDROGEL DRUG DELIVERY

SYSTEMSYSTEM

HYROGELSHYROGELS::-- Three dimensional, water swollen systems.Three dimensional, water swollen systems. Composed ofHydrophilic polymers.Composed ofHydrophilic polymers.

Rendered insoluble due to crosslinking.Rendered insoluble due to crosslinking.

Synthetic Polymers used in Hydrogel DDSSynthetic Polymers used in Hydrogel DDS

PVA, PE, PEG, PMMA, Polyacrylamide, PEA, PEMA, HEMA, PVPPVA, PE, PEG, PMMA, Polyacrylamide, PEA, PEMA, HEMA, PVPPoly (NPoly (N--isopropylacrylamide), Poly dimethyl aminoethyl methacrylate,isopropylacrylamide), Poly dimethyl aminoethyl methacrylate,

Poly (NPoly (N-- Butyl acrylate), Itaconic acid monoester, HPMA,Butyl acrylate), Itaconic acid monoester, HPMA,Poly Ethylene oxide dimethacrylate (PEODM),Poly Ethylene oxide dimethacrylate (PEODM),Poly (2Poly (2-- dimethylamino) ethyl methacrylate (DEAEMA),dimethylamino) ethyl methacrylate (DEAEMA),Poly (2Poly (2-- diethylamino) ethyl methacrylate (DMAEMA)diethylamino) ethyl methacrylate (DMAEMA)

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SYNTHETICBIODEGRADABLESYNTHETICBIODEGRADABLEPOLYMERPOLYMER

PROPERTIES &APPLICABILITYPROPERTIES &APPLICABILITY

A)A) CROSSCROSS--LINKED HYDROGELSLINKED HYDROGELS

Poly (aPoly (a-- amino acids), Polyamino acids), Poly(g(g-- benzylbenzyl--LL--glutamate),glutamate),Polycaprolactone.Polycaprolactone.

INTERPENETRATINGINTERPENETRATINGHYDROGELNETWORKHYDROGELNETWORK likelike--

PCL with HEMAPCL with HEMA

To prepare crossTo prepare cross linked Poly (2linked Poly (2--hydroxyethylhydroxyethyl--LL--glutamine) (PHEG).glutamine) (PHEG).

To enhance polymer compatibility.To enhance polymer compatibility.

To prevent phase separation.To prevent phase separation.

Have hybrid properties.Have hybrid properties.

B)B)NONCROSSNONCROSS--LINKEDLINKEDHYDROGELS/ PHYSICAL GELSHYDROGELS/ PHYSICAL GELS

PEOPEO-- PLABlock copolymerPLABlock copolymer

PVA &PLGABlendPVA &PLGABlend

PEO provides elasticity, hydrophilicityPEO provides elasticity, hydrophilicity

PLA provides mechanical strengthPLA provides mechanical strength

Water uptake depends on PEO conc.Water uptake depends on PEO conc.

HH22O contentO content es from 30es from 30--80% as PVA80% as PVAcontent ed FROM 25content ed FROM 25--95%.95%.

C) GLUCOSEC) GLUCOSE-- SENSITIVESENSITIVEHYDROGELHYDROGEL

Poly (methacrylic acidPoly (methacrylic acid--gg--polypoly

(ethylene glycol)) , PVP, PHEMA,(ethylene glycol)) , PVP, PHEMA,PDMAEMAPDMAEMA

Forms hydogel membrane whichForms hydogel membrane whichimmobilizes GOimmobilizes GO--Enzyme,.Enzyme,.

This system focuses on INSULINThis system focuses on INSULINcontaining Reservoircontaining Reservoir

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SYNTHETICPOLYMERSSYNTHETICPOLYMERS PROPERTIES &APPLICABILITYPROPERTIES &APPLICABILITY

D)D) pHpH-- Sensitive HydrogelsSensitive Hydrogels

Cationic polmersCationic polmers-- Polyacrylamide,Polyacrylamide,PAA, PMMA, PDEAEMA, PDMAEMA.PAA, PMMA, PDEAEMA, PDMAEMA.

Anionic copolymers ofPMMA &Anionic copolymers ofPMMA &PHEMA.PHEMA.

PolyorthoestersPolyorthoesters

havehave NHNH22 as ionizable pendant groupas ionizable pendant group

PDMAEMA &PMMA forms hydrophilicPDMAEMA &PMMA forms hydrophilic

hydrogel containing Caffeine. Thishydrogel containing Caffeine. Thissystem swells in solsystem swells in solnn with p H


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SYNTHETIC POLYMERS USED IN GASTRORETENTIVESYNTHETIC POLYMERS USED IN GASTRORETENTIVE

DRUG DELIVERY SYSTEMS (GRDDS)DRUG DELIVERY SYSTEMS (GRDDS)

GRDDS are Oral controlledGRDDS are Oral controlledDDS.DDS.

Releases drug prior toReleases drug prior toAbsorption window.Absorption window.

Prolongs Drug release rate.Prolongs Drug release rate.

Ensures optimal BA.Ensures optimal BA.

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SYNTHETICPOLYMERSUSED IN GRDDSSYNTHETICPOLYMERSUSED IN GRDDS--

1)1) FLOATING SYSTEMSFLOATING SYSTEMS Matrix formers likeMatrix formers like-- Polystyrene, PMMA, Polyacrylates,Polystyrene, PMMA, Polyacrylates,

Polycarbonates, Polycarbophil &Highly swellable gelPolycarbonates, Polycarbophil &Highly swellable gel-- formingforminghydrocolloid likehydrocolloid like-- HEC, HPMC, HPC, Na CMC.HEC, HPMC, HPC, Na CMC.

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33))SWELLING SYSTEMSSWELLING SYSTEMS Polymer should be swellable, hydrophilic, of appt. mol. Wt.Polymer should be swellable, hydrophilic, of appt. mol. Wt. Swelling depends on degree of crosslinking.Swelling depends on degree of crosslinking.

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SYNTHETIC POLYMERS USED IN CONTROLLEDDDSSYNTHETIC POLYMERS USED IN CONTROLLEDDDS


Poly (DLPoly (DL-- lactidelactide-- coco-- glycolide)glycolide)microspheremicrosphere

For Live Rotavirus vaccine,For Live Rotavirus vaccine,For encapsulatingFor encapsulating -- lactoglolactoglo--

bulin microspheresbulin microspheres

Polyacrylic acidPolyacrylic acid Polyanion excipient to shieldPolyanion excipient to shieldTransforming Growth Factor (TGF)Transforming Growth Factor (TGF)

from inactivation with Alginatesfrom inactivation with Alginates

PolyPoly-- -- caprolactone nanoparticlescaprolactone nanoparticles For encapsulating Cyclosporine AFor encapsulating Cyclosporine A

PolyesterPolyester Tetanus Toxoid (vaccine)Tetanus Toxoid (vaccine)encapsulating microspheres forencapsulating microspheres for

singlesingle-- injection immunizationinjection immunization

CRDDS follows ZeroCRDDS follows Zero-- order release Kinetics.order release Kinetics. Requires swellable polymers which are capable of forming externalRequires swellable polymers which are capable of forming external

gel layer controlling drug release.gel layer controlling drug release.

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SYNTHETIC POLYMERS USED IN CONTROLLED &SYNTHETIC POLYMERS USED IN CONTROLLED &

TARGETEDDRUG DELIVERY SYSTEMSTARGETEDDRUG DELIVERY SYSTEMS

SYNTHETICPOLYMERSUSED INNANOPARTICLE DRUG DELIVERYSYNTHETICPOLYMERSUSED INNANOPARTICLE DRUG DELIVERYSYSTEMSSYSTEMS

Nanoparticles are subNanoparticles are sub--micron sized colloidal structures.micron sized colloidal structures.

Ist Nanoparticles were based on NonIst Nanoparticles were based on Non--Biodegradable polymers likeBiodegradable polymers likePolyacrylamide, PS, PMMA.Polyacrylamide, PS, PMMA.

Now, Biodegradable polymers like Poly(cyanoacrylates) were used inNow, Biodegradable polymers like Poly(cyanoacrylates) were used inNP.NP.

Synthetic Hydrophobic polymers used in NPSynthetic Hydrophobic polymers used in NP--

PCL, PLA, PLGA, PS.PCL, PLA, PLGA, PS.

PMMA, PICA, PBCA, PHCAPMMA, PICA, PBCA, PHCA

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SYNTHETICPOLYMERSYNTHETICPOLYMER PROPERTIES &APPLICABILITYPROPERTIES &APPLICABILITY

1)1) FOR STEALTHNPFOR STEALTHNP

POLAXAMERPOLAXAMER-- ABABlock str.ABABlock str.

PEO/PEGPEO/PEG--PPO/PPGPPO/PPG--PEO/PEGPEO/PEG

POLAXAMINESPOLAXAMINES-- TetrafunctionalTetrafunctionalblock copolymer with centralblock copolymer with centralethylenediamine bridgeethylenediamine bridge

(PEO(PEO--PPO)PPO)22--XX--(PPO(PPO--PEO)PEO)22 (PEG(PEG--PPG)PPG)22--XX--(PEG(PEG--PPG)PPG)22

Forms hydrated, hydrophillic stericForms hydrated, hydrophillic stericbarrier on NP surface.barrier on NP surface.

To modify PSTo modify PS-- NP surface to deliverNP surface to deliverSalmon Calcitonin.Salmon Calcitonin.

2)2)FOR BIOADHESIONOFNPFOR BIOADHESIONOFNP Polyacrylic acid (Carbomer/Polyacrylic acid (Carbomer/Carbopol)Carbopol)

Swells 1000 times in HSwells 1000 times in H22O &O &provides Controlled release.provides Controlled release.

3)3)FOR OCCULAR DELIVERYFOR OCCULAR DELIVERY

Polyalkyl cyanoacrylatesPolyalkyl cyanoacrylates PCL, Polyester, PVA, HPMCPCL, Polyester, PVA, HPMC

Adheres to conjuctival mucin &Adheres to conjuctival mucin &residence time of NP in precorneal area.residence time of NP in precorneal area.

To deliver Pilocarpine & BetaxololTo deliver Pilocarpine & Betaxolol

4)4)FOR BRAIN TARGETINGFOR BRAIN TARGETING

Polybutyl cyanoacrylates coatedPolybutyl cyanoacrylates coatedwith Polysorbatewith Polysorbate-- 8080

To deliver Hexapeptide dalargin,To deliver Hexapeptide dalargin,MetMet-- enkephalin Kyotropin,enkephalin Kyotropin,Doxorubicin.Doxorubicin.

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5)5)FOR LYMPHATIC TARGETINGFOR LYMPHATIC TARGETING

Polyalkyl cyanoacrylatesPolyalkyl cyanoacrylates

(PEO(PEO--PLys) block copolymerPLys) block copolymer

To deliver Insulin for peroral peptideTo deliver Insulin for peroral peptidedelivery through Peyers pathes.delivery through Peyers pathes.

Conjugated to cisConjugated to cis-- diaminedichlorodiaminedichloro--Platinum (cDDP) to treat lymph nodePlatinum (cDDP) to treat lymph nodemetastases.metastases.

6)6)FOR TUMOR TARGETINGFOR TUMOR TARGETING

PolyalkylcyanoacrylatesPolyalkylcyanoacrylates

PolybutylcyanoacrylatesPolybutylcyanoacrylates

PolyisobutylcyanoacrylatesPolyisobutylcyanoacrylates

NN--(2(2--HPMA)HPMA)

To deliver Doxorubicin.To deliver Doxorubicin.

To deliver Mitoxantrone, Acyclovir.To deliver Mitoxantrone, Acyclovir.

To deliver AdacinomycinTo deliver Adacinomycin

Act as lysosmotropic drug carrier for siteAct as lysosmotropic drug carrier for sitespecific delivery of MAb (IgG, Ab B72.3)specific delivery of MAb (IgG, Ab B72.3)

7)7)ADJUVANT EFFECT FORADJUVANT EFFECT FORVACCINESVACCINES

PMMAPMMA For Inluenza Ag & adjuvant to HIVFor Inluenza Ag & adjuvant to HIV--22whole virus vaccine.whole virus vaccine. 4141


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SYNTHETIC POLYMERS USED INSYNTHETIC POLYMERS USED INMICELLAR DRUG DELIVERYMICELLAR DRUG DELIVERY

SYSTEMSYSTEM

Polymeric Micelles are few tens in nm ,Polymeric Micelles are few tens in nm ,crosslinked combination of hydrophilic & hydrophobiccrosslinked combination of hydrophilic & hydrophobic

monomers.monomers.

Forms shellForms shell-- like structure , hydrophilic portion forms outer shell &like structure , hydrophilic portion forms outer shell &it protects core contents from chemical attacks in aqueous media init protects core contents from chemical attacks in aqueous media inwhich they travels.which they travels.

Drug release occur via polymer degradation.Drug release occur via polymer degradation.

Have low CMC, slow dissociation rate & long retention of loaded drugHave low CMC, slow dissociation rate & long retention of loaded drugas compared to surfactant micelle.as compared to surfactant micelle. 4242


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A)A) pHpH--sensitive Micelle based on titrable groupssensitive Micelle based on titrable groups Synthetic block copolymers containing weak basic groupSynthetic block copolymers containing weak basic group::-- Poly(2Poly(2--Vinyl pyridine)Vinyl pyridine)--bb--PEO, PEOPEO, PEO--DMAEMA, PDMAEMADMAEMA, PDMAEMA--bb--PDAEMA,PDAEMA,

PEOPEO--bb--DMAEMADMAEMA--bb--DEAEMA, DMAEMADEAEMA, DMAEMA--bb--Poly[2Poly[2--(N(N--morpholino)ethylmorpholino)ethyl

methacrylate.methacrylate.

Copolymers containing weak acidic groupsCopolymers containing weak acidic groups ::-- Poly[sodiumPoly[sodium--22--(acrylamido)(acrylamido)--22--methyl propanesulfonatemethyl propanesulfonate--bb--polypoly

(sodium(sodium--66--acryl amido hexanoate) &Poly(sodiumacryl amido hexanoate) &Poly(sodium--44--styrenestyrenesulfonate)sulfonate)--bb--Poly(sodiumPoly(sodium--44--vinyl benzoate)vinyl benzoate)

Forms micelle at pH

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