Targeted drug delivery systems

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2. CONTENTS INTRODUCTION NEED OF TDDS ADVANTAGES & DISADVANTAGES IDEAL TDDS CARRIERS STRATEGIES SYSTEMS MICROSPHERES: MAGNETIC MICROSPHERE NANOPARTICLES 3. INTRODUCTION Targeted drug delivery(Smart Drug Delivery) means selective and effectivelocalization of drug into the target at therapeutic concentrations withlimited access to non target sites . The drug can be targeted to an organ particular tissue or cell intracellular sites virus or bacterial cellsGOAL - prolong ,localize, target, and have a protected drug interaction with thediseased tissue. 4. NEED OF TARGETED DRUG DELIVERY 5. Advantages and DisadvantagesADVANTAGES Reduction of drug side-effects Reduced frequency of drugintake Reduced dose of drug Uniform blood level of drug Maximizes the therapeuticindexDISADVANTAGES Rapid clearance of targetedsystems Immune reaction againstcarrier systems Insufficient localization oftargeted systems in tumorcells Diffusion and redistribution ofreleased drug High cost 6. PROPERTIES OF IDEAL TDDS It should be -o Non-toxico Biocompatibleo Biodegradableo Physicochemical stable both in-vivo & in-vitro Controlled and predictable drug release Minimal drug leakage Carrier should be readily eliminated without causing any change indiseased state Preparation should be easy, reproductive and cost effective Drug release should not effect drug action 7. CARRIERS OR MARKERSEngineered vectors which retain drug inside or onto them to delivery itwithin or vicinity of target.PROPERTIES Cross anatomical barriers; tumor vasculature Linkage to be stable in biological fluids Selectively and specifically recognize target cells 8. STRATEGIES OF DRUG TARGETING 9. Passive or InversePASSIVE DDS targets the systemiccirculation of body Drug targeting occurs due tobodys natural response to thephysicochemical properties ofdrug or carrier system Example: uptake of some colloidsby RES especially in liver or spleen=> ideal substrate for passivehepatic targeting of drugINVERSE Uptake of the DDS like colloids byRES is avoided, hence calledINVERSE TARGETING Example: preinjection of largeamount of blank colloidal carriersor macromolecules like dextran tosaturate the RES system => drugtargeting to NON-RES ORGANS 10. ACTIVE TARGETING Carrier system is modified on its surface to deliver drug to a specificsite FIRST ORDER: distribution to the capillary bed of target site likelymphatic, cerebral ventricles etc. SECOND ORDER: delivery to special cells like tumor or kupffer cellsin liver. THIRD ORDER: intracellular localization of dug carrier complex viaendocytosis or ligand mediated entry where lysosomal degradationof carrier complex causes release of drug. 11. TARGETING STRATEGIESDUAL TARGETING CARRIER MOLECULE also has their own therapeutic activity and thus increasestherapeutic effect of drug Net SYNERGISTIC EFFECT of drug conjugateDOUBLE TARGETING TEMPORAL & SPATIAL methodologies are combined in a delivery system SPATIAL PLACEMENT : targeting drugs to specific organs, tissues orsubcellular compartments TEMOPAL DELIVERY :controlling the rate of drug delivery 12. CARRIER SYSTEMS Colloidal carriers Cellular carriers: erythrocytes, platelets, antibodies Supramolecular delivery system:micelles, lipoproteins(VLDL,LDL) Polymer based system Macromolecular carrier:MABS, polysaccharides 13. COLLOIDAL CARRIER SYSTEMS Vesicular systems Liposome Virosome Pharmacosome Microparticulate systems Nanoparticles Microspheres 14. MICROSPHERES Microspheres are small spherical particles,with diameters in the micrometer range(typically 1 m to 1000 m). Also called as - Microparticles Microbeads 15. MATERIALS USED NATURAL POLYMERS Proteins: albumin, gelatin, collagen Carbohydrates: starch, agarose Chemically modified carbohydrates: poly(acryl) dextran, poly(acryl)starch SYNTHETIC POLYMERS Biodegradable: lactides & their gylcolides, polyanhydrides Non-biodegradable: polymethyl methacrylate,acrolein 16. TYPES OF MICROSPHERENATURE DESCRIPTION IMAGE APPLICATIONBIO ADHESIVE Intimate contactwith absorption siteProlongedresidence timeNasal:gentamycin,insulinOcular:methylprednisoloneFLOATING(GRDDS)Bulk density lessthan gastric fluid2 types : hollow: microballonNSAIDS,antibiotics 17. TYPES OF MICROSPHERENATURE DESCRIPTION IMAGE APPLICATIONRADIO ACTIVEMICROSPHERESRadionuclide tightlybound tomicrobeadAlpha:10cell layerBeta:Not more than12mmGamma:several cmDiagnostic(gamma):spleen,liver imagingTherapeutic(alpha/beta):radioembolization therapyPOLYMERICMICROSPHERESBiodegradableNon-biodegradableSwell in aqueousmediumVaccine :hepatitisLocal:protein,hormones 18. MAGNETIC MICROSPHERE Supramolecular particles small enough to circulate throughcapillaries without producing embolic occlusion But are to be captured in micro vessels Dragged into the adjacent tissue by magnetic field of 0.5-0.8 Tesla Magnetite(Fe3O4) : ferromagnetic material that is incorporated inmicrospheres to make them magnetically responsive 19. TARGETING OF MAGNETIC MICROBEAAD 20. REALEASE OF DRUG Freely moves through the capillaries Application of external magnetic field result in accumulation of drugat target site 21. APPLICATIONS OF MAGNETIC MICROBEADS Localization of therapeutic agent Bioengineering & biomedical trends like enzymeimmobilization, protein purification, cell isolation DNA analysis Drug discovery Molecular targeting 22. PREPARATION OF MICROSPHERESMETHOD DESCRIPTION APPLICATIONEmulsion solventevaporationDrug+polymer sol=>toaqueous phase(PVP) =EMULSION(O/W)=>evaporate solvent =microsphereAceclofenacmicrospheresHollow microspheresEmulsion crosslinkingDrug=+Gelatin sol=>add dropsto liquidparaffin=emulsion(W/O)=>MICROBEADS washed withisopropyl alcohol=>add toglutaraldehyde solGelatin Amicrospheres 23. PREPARATION OF MICROSPHERESMETHOD DESCRIPTION APPLICATIONCo-acervation Drug+Polymer sol=>phaseseparation -change in T,pH-salt or non solvent additionProteinsSteroidsEmulsion-solventdiffusionDrug polymermix+ethanol:dichloromethane(1:1)=>add dropwise to SLSsol=agitate at 40C =>microbeads driedMicroballonsIonic gelation Diclofenac sodium+ sodiumalginate aq sol=>add to Ca2+& chitosan sol in acetic acid =microsphere kept for 24 hrsfor internal gellificationDiclofenac sodium=> drugrelease at pH6.4-7.2 24. COACERVATION METHOD 25. NANOPARTICLES 1-100 nanometer in size Also called ULTRAFINEPARTICLES NANOTECHNOLOGY defines particle as a small object that behavesas a whole unit with respect to its transport and properties 26. PROPERTIES High surface area- volume ratio Act as bridge between bulk materials and atomic/molecularstructures Size dependent properties are observed Possess unexpected optical properties as they are smallenough to confine their electrons and produce quantumeffects 27. TYPES OF NANOPARTICLESNANO-CARRIERDESCRIPTION IMAGE APPLICATIONNANOSHELLSHollow silicaspheres coveredwith goldTargeting tumorcellsNANOWIRESMetallic:Au,NiSemiconducting:Si, InPInsulating:SiO2Detect tumor inbrain,treatmentof Parkinson's 28. TYPES OF NANOPARTICLESQUANTAMDOTSMinisculesemiconductorparticlesTargetingcancerous cellsGOLDNANOPARTICLESUltra sensitivedetection systemfor DNA&proteinsGeneticengineeringDENDRIMERS Syntheticnanoparticle,510nm diameterMedicalimaging,genetransfection 29. PREPARATION OF NANOPARTICLES TOP DOWNAttrition : broad size distribution (10-1000 nm): varied particle shape or geometry: impurities BOTTOMS UP METHODSo Vapor phase fabrication: pyrolysiso Liquid phase fabrication: sol gel method 30. Fabrication 31. Marketed drugsBRAND GENERICNAMEINDICATION COMPANYTricor Fenofibrate HypercholesterolemiaAbbottLaboratoriesAvinza MorphinesulphatePsycho stimulant Elan nanosystemsRapamune Rapamycin immunosuppresantElan nanosystems