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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SYNTHETICPOLYMERSYNTHETICPOLYMER APPLICABILITYAPPLICABILITY
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.
They hydrates, swells & maintains density
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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
SYNTHETICPOLYMERSYNTHETICPOLYMER APPLICABILITYAPPLICABILITY
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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SYNTHETICPOLYMERSYNTHETICPOLYMER APPLICABILITYAPPLICABILITY
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