Recent updates in synthetic polymers used in drug delivery systems

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<ul><li>1.Recent updates in synthetic polymers used in drug delivery systems KUSUM SINGHNEELAM SINGH I.T.S. PHARMACY COLLEGE,GHAZIABAD, INDIA</li></ul> <p>2. CONTENTS </p> <ul><li>INTRODUCTION </li></ul> <ul><li>DEFINITION </li></ul> <ul><li>CLASSIFICATION </li></ul> <ul><li>PROPERTIES &amp; SELECTION OF SYNTHETICPOLYMERS </li></ul> <ul><li>SYNTHETIC POLYMERS USED IN DRUG DELIVERY SYSTEMS </li></ul> <p>3. INTRODUCTION </p> <ul><li>Significant advances have been made in development of various drug delivery devices with the help of polymers. </li></ul> <ul><li>The earliest DDS first introduced in 1970s were based on polymers formed from lactic acid. </li></ul> <ul><li>Today polymeric materials still provides most important avenues of research primarily because of ease of processing &amp; ability of researchers to readily control their chemical &amp; physical properties via. Molecular system. </li></ul> <p>4. DEFINITION </p> <ul><li>POLYMERS :- </li></ul> <ul><li>Compounds with high molecular masses formed by combination of large number of simple molecules called as monomers. </li></ul> <ul><li>Prepared by addition / condensation polymerization. </li></ul> <ul><li>In Greek ,Polymeans many &amp;merosmeans units/parts. </li></ul> <ul><li>Polymers are of 3 types:- </li></ul> <ul><li>Natural, Semisynthetic, Synthetic. </li></ul> <p>5. CLASSIFICATION OF SYNTHETIC POLYMERS ON THE BASIS OFSTRUCTURE BRANCHED CHAIN POLYMERS EXAMPLES :- Low Density Polythene CROSS LINKED POLYMERSEXAMPLES:- Bakelite, MF Resin LINEAR POYMERS EXAMPLES :- PEG, Polyesters 6. CONTD ON THE BASIS OFDEGRADABILITY OFPOLYMERS BIODEGRADABLE POLYMERS NONBIODEGRADABLE POLYMERS ENVIRONMENT RESPONSIVE POLYMERS ELECTRICALLY &amp;CHEMICALLYCONTROLLED POLYMERS THERMOSENSITIVE POLYMERS pH-SENSITIVE POLYMERS 7. SYNTHETIC POLYMER:- CLASS EXAMPLES </p> <ul><li>BIODEGRADABLE POLYMERS </li></ul> <ul><li>POLYESTERS </li></ul> <ul><li>POLYANHYDRIDES </li></ul> <ul><li>POLYAMIDE </li></ul> <ul><li>PHOSPHOROUSBASED </li></ul> <ul><li>OTHERS </li></ul> <p>PLA, PGA, PHB PCL, PMA, POLYDIOXANONES POLYSEBACIC ACID, PTA POLYPHOSPHAZENES, POLYPHOSPHONATE POLYCYANOACRYLATES, POLYURETHENES, POLYORTHOESTERS B)NONBIODEGRADABLE CELLULOSE DERIVATIVE SILICONES ACRYLIC POLYMERS OTHERS CMC, EC, CA, CAP PDS, COLLOIDAL SILICA PMA, PMMA, PHEMA PVP, EVA. POLYOXAMER 8. ON THE BASIS OFMONOMERIC UNITS CONTD HOMOPOLYMERS COPOLYMERS GRAFTED COPOLYMERS ALTERNATING COPOLYMERS BLOCK COPOLYMERS RANDOM COPOLYMERS 9. PROPERTIES &amp; SELECTION OF POLYMERS </p> <ul><li>POLYMER IS CHOOSEN ON BASIS OF:- </li></ul> <ul><li>Physicochemical properties </li></ul> <ul><li>Need for biochemical characterization. </li></ul> <ul><li>Chemical composition </li></ul> <ul><li>Micro structural design </li></ul> <ul><li>Surface properties like lubricity, hydrophilicity, smoothness, surface energy </li></ul> <p>10. PROPERTIES OF SYNTHETIC POLYMER THAT NEED TO BE CONSIDERD FOR APPLICATION OF POLYMERS TO DRUG DELIVERY SYSTEMS </p> <ul><li>Solubility </li></ul> <ul><li>Viscosity </li></ul> <ul><li>Polymer- Solvent interaction </li></ul> <ul><li>Crystallinity </li></ul> <ul><li>Polymer dissolution </li></ul> <ul><li>Bioadhesivity of Hydrophilic polymer </li></ul> <ul><li>Polymer erosion &amp; Biodegradation </li></ul> <p>11. SYNTHETIC POLYMERS USED IN DRUG DELIVERYSYSTEMS </p> <ul><li>SYNTHETIC POLYMERS IN DENDRITIC</li></ul> <ul><li>DRUG DELIVERY SYSTEMS </li></ul> <ul><li>DENDRIMERS- </li></ul> <ul><li>Transport extremely high</li></ul> <ul><li>densities of drug molecules. </li></ul> <ul><li>It is suitable carrier system because:- </li></ul> <ul><li>Their size &amp; structure can be controlled. </li></ul> <ul><li>Encapsulate small drug molecule to form Polymer micelles. </li></ul> <ul><li>Serves as hubs onto which large number of drug molecules can attached via covalent bond. </li></ul> <p>12. </p> <ul><li>PAMAM DendrimerUsed in gene delivery. It has amine </li></ul> <ul><li>Terminal group which binds to DNA by electrostatic charge. </li></ul> <ul><li>Prepared either as Divergent /Convergent type. </li></ul> <ul><li>Starburst TMPAMAM dendrimer in intact(Polyfect (R) )&amp;</li></ul> <ul><li>fractured form(Superfect ). </li></ul> <ul><li>Fractured form shows better gene expression. </li></ul> <ul><li>Polyethyleneimine(PEI)-</li></ul> <ul><li>To prepare PEI- gene complex. </li></ul> <ul><li>After internalization release of gene complex by endosome occurs due to</li></ul> <ul><li>protonation of internal 3 Nitrogen by endosomal protons </li></ul> <ul><li>which then results in swelling of endosome &amp; ultimately</li></ul> <ul><li>releases DNA. </li></ul> <p>13. 14. SYNTHETIC POLYMER APPLICABILITY Poly Amino Amine dendrimer </p> <ul><li>To deliver 5-Fluro uracil. </li></ul> <ul><li>For occular drug delivery ofPilocarpine Nitrate. </li></ul> <ul><li>Increases solubility of Nifedipine </li></ul> <p>Poly aryl ether dendrimer To deliver Methotrexate 15. SYNTHETIC POLYMER USED IN MUCOADHESIVE BUCCAL DRUG DELIVERY SYSTEMS </p> <ul><li>Factors to be considered:- </li></ul> <ul><li>Chain flexibility </li></ul> <ul><li>Low molecular weight </li></ul> <ul><li>Ability to form H-bonding </li></ul> <ul><li>Concentration &amp; swelling of polymers. </li></ul> <ul><li>Synthetic Polymers used as Permeation enhancers :- </li></ul> <p>CLASS SYNTHETIC POLYMERS SURFACTANTS Polyoxyethylene, Polyoxyethylene-9-lauryl ether,Polyoxyethylene-20-cetyl etherTHIOLATED POLYMERS Polycarbophil, Polyacrylic acid 16. BIOADHESIVE POLYMERS IN MUCOADHESIVEDRUG DELIVERY SYSTEMS BIOADHESIVE PROPERTIES CHARACTERISTICS Poly-hydroxyl Butyrate Poly(e-caprolactone) Polyorthoesters Polyphosphazenes Polycyanoacrylates Polyvinyl Acetate Polyethyleneoxide-b-propylene oxide Biodegradable Properties can be changed by chemical modification Surface eroding polymer Can be tailored with versatile side chain functioning Biodegradable Biocompatible Amphiphillic surfactant Biocompatible Matrix for DDS Cell encapsulation Sustained DDS, opthalmology To make films, Hydrogels in DDS Surgical adhesives, glues in DDS Gels &amp; Blended membranes in DD &amp; Immobilization Protein delivery 17. SYNTHETIC POLYMERS USED IN SUSTAINED RELEASE DRUG DELIVERY SYSTEMS </p> <ul><li>Sustained Release DDS follows 1 storder release kinetics. </li></ul> <ul><li>Increased crosslinking of polymers decreases diffusion rate &amp; thus improves sustained release properties of polymers &amp; decreases mucoadhesivity. </li></ul> <ul><li>Synthetic Absorbable Polymers- include homopolymers like PLA, PGA, PCL, Polytrimethylene carbonate, Poly(p-dioxanone) &amp; copolymers like- Poly lactide-co-glycolide, Poly (glycolide-co-trimethylene carbonate). </li></ul> <p>18. SYNTHETIC POLYMER APPLICABILITY Poly(Monosteroyl Glycerol-co-succinate) For Sustained release of Theophylline/ Risperidone from microparticles in-vitro Polyvinyl Acetate For sustained release capsules of Nifedipine Eudragit RLPM, RSPM &amp; HPMC Sustained release of theophylline 19. SYNTHETIC POLYMER BASED VECTORS IN GENE THERAPY </p> <ul><li>Cationic Polymersof high mol. wt. is used. </li></ul> <ul><li>Synthetic Polymers used:- </li></ul> <ul><li>PAMAM, Poly(4-Vinyl imidazole), PPL-Poly-L-lysine, PDMAEMA. </li></ul> <ul><li>Poly-L-lysine :-Biodegradable, lacks NH 2gp. with a pK abetween 5 &amp; 7 allowing no endosmolysis, resulting in low transgene expression. </li></ul> <ul><li>This drawback requires inclusion of endosmolytic agent like Fusogenic peptide like </li></ul> <ul><li>Copolymer of Poly-L-lysine with Poly-L-histidine/ L-tryptophan. </li></ul> <ul><li>Polyethyleneimine-Shows efficient transfecting ability without use of fusogenic agent. </li></ul> <ul><li>PEI offers high charge density due to which it offers increased protection against serum nucleases. </li></ul> <p>20. 21. SYNTHETIC POLYMERS USED IN OPTHALAMIC DRUG DELIVERY SYSTEMS </p> <ul><li>Properties of syntheticPolymers considered for Opthalamic DDS- </li></ul> <ul><li>Non-Toxic, Biodegradable, Biocompatible, Optically transparent, Do not impede vision, Tolerable, good retention properties, mucoadhesivity. </li></ul> <ul><li>Non-Biodegradable polymeric bioadhesives used as drug delivery systems:- </li></ul> <ul><li>Copolymers based on Vinylpyrrolidone, Methacrylicacid, Polydimethylene- siloxane, Poly (N-isopropyl acrylamide), PAMAM dendrimers. </li></ul> <p>22. CONTD SYNTHETIC POLYMERS APPLICABILITY Polyhydroxy ethyl -methacrylate Used to formulate liposomes loaded with Dimyristoyl phosphatidylcholine (DMPC). It is optically transparent &amp; release drug for a period of 8days. Poly (D,L-lactide)Biodegradable polymer used for sustained retinal delivery of Celecoxib to inhibit diabetes induced Retinal oxidative demage Polyanhydrides, Polyorthoesters For sustained release of 5-FU Poly (-caprolactone) rod shaped implants Tolerated by retinal tissues &amp; used to release corticosteroid triamcinolone acetide over 4 weeks 23. SYNTHETC POLYMERS USED IN TRANSDERMAL DRUG DELIVERY SYSTEM </p> <ul><li>Polymers are the backbone of TDDS. </li></ul> <ul><li>TDDS are fabricated as multilayered polymeric laminates or drug- polymer matrix is sandwiched between two polymeric layers i.e. backing layer &amp; inner polymeric layer which act as adhesive &amp; Rate- controlling membrane. </li></ul> <ul><li>TDDS is formulated either as Matrix form / Reservoir form. </li></ul> <p>24. IN TDDS POLYMERS ACTS AS MATRIX FORMERS BACKING LAYERS RELEASE LINERS RATE CONTROLING MEMBRANE PRESSURE- SENSITIVEADHESIVES (PSAs) 25. </p> <ul><li>MATRIX FORMERS</li></ul> <ul><li>Selected on the basis of:- </li></ul> <ul><li>Release properties </li></ul> <ul><li>Adhesion cohesion balance </li></ul> <ul><li>Physicochemical properties </li></ul> <ul><li>e.g.-Monolithic solid state design is preffered for Passive TDDS </li></ul> <ul><li>Synthetic polymers used- </li></ul> <ul><li>Cross linked PEG network </li></ul> <ul><li>Biocompatible </li></ul> <ul><li>Used for protein drug delivery. </li></ul> <ul><li>b)Acrylic acid matrices </li></ul> <ul><li>Acrylic acid + Plasticizer :- used to make drug- polymer matrix</li></ul> <ul><li>film.</li></ul> <ul><li>Eudragit RLPM, Eudragit S-100, Eudragit E-100, ethyl acetate</li></ul> <ul><li>&amp; MMA </li></ul> <p>26. </p> <ul><li>c)Polyvinylpyrrolidone </li></ul> <ul><li>Matrix formers with 30% Dibutyl Phthalateto deliver Diltiazem</li></ul> <ul><li>Hydrochloride &amp; Domethacin </li></ul> <ul><li>d)HPMC </li></ul> <ul><li>Hydrophillic, swellable polymer used for Oral Controlled DDS </li></ul> <ul><li>Matrix formers in Propranolol HCl </li></ul> <ul><li>For fast release of drug. </li></ul> <ul><li>2)RATE CONTROLLING MEMBRANE </li></ul> <ul><li>Ethyl Vinyl Acetate </li></ul> <ul><li>By altering Vinyl Acetate content membrane permeability can be controlled </li></ul> <ul><li>b)Silicone Rubber </li></ul> <ul><li>Biocompatible </li></ul> <ul><li>Highly permeable to steroids </li></ul> <ul><li>Ease of fabrication </li></ul> <ul><li>Low microscopic viscosity &amp; used in Controlled Release devices. </li></ul> <p>27. </p> <ul><li>c) Poly Urethane </li></ul> <ul><li>Rubbery &amp; increased permeability </li></ul> <ul><li>Two types:- Polyether urethanes &amp; Polyester Urethanes </li></ul> <ul><li>Due tomore BiodegradabilityPolyester Urethanes are more </li></ul> <ul><li>preffered. It is used for Hydrophillic polar drugs. </li></ul> <ul><li>PRESSURE SENSITIVE ADHESIVES </li></ul> <ul><li>Characteristic of visco- elastic material </li></ul> <ul><li>Poly Iso Butylene </li></ul> <ul><li>Formed by cationic polymers </li></ul> <ul><li>b)Poly Acrylates </li></ul> <ul><li>Amorphous, gives water clear color in solution &amp; stable towards </li></ul> <ul><li>ageing &amp; have good mechanical properties. </li></ul> <ul><li>c) Silicones </li></ul> <ul><li>Contains low viscosity Dimethyl siloxane polymer. </li></ul> <ul><li>Silicate Resin + PDMSundergoes condensation to form Silicone PSA </li></ul> <p>28. 4)BACKING MATERIALS 29. 30. SYNTHETIC POLYMERS USED IN HYDROGEL DRUG DELIVERYSYSTEM </p> <ul><li>HYROGELS :-</li></ul> <ul><li>Three dimensional, water swollen systems. </li></ul> <ul><li>Composed of Hydrophilic polymers. </li></ul> <ul><li>Rendered insoluble due to crosslinking. </li></ul> <ul><li>Synthetic Polymers used in Hydrogel DDS </li></ul> <ul><li>PVA, PE, PEG, PMMA, Polyacrylamide, PEA, PEMA, HEMA, PVP </li></ul> <ul><li>Poly (N-isopropylacrylamide), Poly dimethyl aminoethyl methacrylate, </li></ul> <ul><li>Poly (N- Butyl acrylate), Itaconic acid monoester, HPMA, </li></ul> <ul><li>Poly Ethylene oxide dimethacrylate (PEODM), </li></ul> <ul><li>Poly (2- dimethylamino) ethyl methacrylate (DEAEMA), </li></ul> <ul><li>Poly (2- diethylamino) ethyl methacrylate (DMAEMA) </li></ul> <p>31. SYNTHETIC BIODEGRADABLE POLYMER PROPERTIES &amp; APPLICABILITY </p> <ul><li>CROSS-LINKED HYDROGELS </li></ul> <ul><li>Poly (a- amino acids), Poly (g- benzyl-L-glutamate), Polycaprolactone. </li></ul> <ul><li>INTERPENETRATING HYDROGEL NETWORKlike- </li></ul> <ul><li>PCL with HEMA </li></ul> <ul><li>To prepare cross linked Poly (2- hydroxyethyl-L-glutamine) (PHEG). </li></ul> <ul><li>To enhance polymer compatibility. </li></ul> <ul><li>To prevent phase separation. </li></ul> <ul><li>Have hybrid properties. </li></ul> <ul><li>B)NON CROSS-LINKED HYDROGELS/ PHYSICAL GELS </li></ul> <ul><li>PEO- PLA Block copolymer </li></ul> <ul><li>PVA &amp; PLGA Blend </li></ul> <ul><li>PEO provides elasticity, hydrophilicity </li></ul> <ul><li>PLA provides mechanical strength </li></ul> <ul><li>Water uptake depends on PEO conc. </li></ul> <ul><li>H 2 O contentes from 30-80% as PVA content ed FROM 25-95%. </li></ul> <ul><li>C) GLUCOSE- SENSITIVE HYDROGEL </li></ul> <ul><li>Poly (methacrylic acid-g-poly (ethylene glycol)) , PVP, PHEMA, PDMAEMA </li></ul> <ul><li>Forms hydogel membrane whichimmobilizes GO-Enzyme,. </li></ul> <ul><li>This system focuses on INSULIN containing Reservoir </li></ul> <p>32. SYNTHETIC POLYMERS PROPERTIES &amp; APPLICABILITY </p> <ul><li>D)pH- Sensitive Hydrogels </li></ul> <ul><li>Cationic polmers- Polyacrylamide, PAA, PMMA, PDEAEMA, PDMAEMA. </li></ul> <ul><li>Anionic copolymers of PMMA &amp; PHEMA. </li></ul> <ul><li>Polyorthoesters </li></ul> <ul><li>have NH 2as ionizable pendant group </li></ul> <ul><li>PDMAEMA &amp; PMMA forms hydrophilic hydrogel containing Caffeine. This system swells in sol nwith p H</li></ul>


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