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Targeted drug delivery systems
- 1. TARGETED DRUG DELIVERY SYSTEM SHIPRA MALIK PHARMACEUTICS
- 2. CONTENTS • INTRODUCTION • NEED OF TDDS • ADVANTAGES & DISADVANTAGES • IDEAL TDDS • CARRIERS • STRATEGIES • SYSTEMS • MICROSPHERES: MAGNETIC MICROSPHERE • NANOPARTICLES
- 3. INTRODUCTION • Targeteddrug delivery(Smart Drug Delivery) means selective and effective localization of drug into the target at therapeutic concentrations with limited access to non target sites . • The drug can be targeted to an organ particular tissue or cell intracellular sites virus or bacterial cells GOAL - prolong ,localize, target, and have a protected drug interaction with the diseased tissue.
- 4. NEED OF TARGETEDDRUG DELIVERY
- 5. Advantages and Disadvantages ADVANTAGES • Reduction of drug side-effects • Reduced frequency of drug intake • Reduced dose of drug • Uniform blood level of drug • Maximizes the therapeutic index DISADVANTAGES • Rapid clearance of targeted systems • Immune reaction against carrier systems • Insufficient localization of targeted systems in tumor cells • Diffusion and redistribution of released drug • High cost
- 6. PROPERTIES OF IDEALTDDS • It should be - o Non-toxic o Biocompatible o Biodegradable o Physicochemical stable both in-vivo & in-vitro • Controlled and predictable drug release • Minimal drug leakage • Carrier should be readily eliminated without causing any change in diseased state • Preparation should be easy, reproductive and cost effective • Drug release should not effect drug action
- 7. CARRIERS OR MARKERS Engineered vectors which retain drug inside or onto them to delivery it within 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 DRUGTARGETING
- 9. Passive or Inverse PASSIVE • DDS targets the systemic circulation of body • Drug targeting occurs due to body’s natural response to the physicochemical properties of drug or carrier system • Example: uptake of some colloids by RES especially in liver or spleen => ideal substrate for passive hepatic targeting of drug INVERSE • Uptake of the DDS like colloids by RES is avoided, hence called INVERSE TARGETING • Example: preinjection of large amount of blank colloidal carriers or macromolecules like dextran to saturate the RES system => drug targeting to NON-RES ORGANS
- 10. ACTIVE TARGETING •Carrier system is modified on its surface to deliver drug to a specific site • FIRST ORDER: distribution to the capillary bed of target site like lymphatic, cerebral ventricles etc. • SECOND ORDER: delivery to special cells like tumor or kupffer cells in liver. • THIRD ORDER: intracellular localization of dug carrier complex via endocytosis or ligand mediated entry where lysosomal degradation of carrier complex causes release of drug.
- 11. TARGETING STRATEGIES DUALTARGETING • CARRIER MOLECULE also has their own therapeutic activity and thus increases therapeutic effect of drug • Net SYNERGISTIC EFFECT of drug conjugate DOUBLE TARGETING • TEMPORAL & SPATIAL methodologies are combined in a delivery system • SPATIAL PLACEMENT : targeting drugs to specific organs, tissues or subcellular 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 • Microspheresare small spherical particles, with diameters in the micrometer range (typically 1 μm to 1000 μm). • 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 MICROSPHERE NATURE DESCRIPTION IMAGE APPLICATION BIO ADHESIVE •Intimate contact with absorption site •Prolonged residence time Nasal :gentamycin,insulin Ocular:methylpredni solone FLOATING (GRDDS) •Bulk density less than gastric fluid •2 types : hollow : microballon NSAIDS, antibiotics
- 17. TYPES OF MICROSPHERE NATURE DESCRIPTION IMAGE APPLICATION RADIO ACTIVE MICROSPHERES Radionuclide tightly bound to microbead Alpha:10cell layer Beta:Not more than 12mm Gamma:several cm Diagnostic(gamma): spleen,liver imaging Therapeutic(alpha/ beta):radioemboliza tion therapy POLYMERIC MICROSPHERES •Biodegradable •Non-biodegradable •Swell in aqueous medium Vaccine :hepatitis Local:protein,horm ones
- 18. MAGNETIC MICROSPHERE •Supramolecular particles small enough to circulate through capillaries 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 in microspheres to make them magnetically responsive
- 19. TARGETING OF MAGNETICMICROBEAAD
- 20. REALEASE OF DRUG • Freely moves through the capillaries • Application of external magnetic field result in accumulation of drug at target site
- 21. APPLICATIONS OF MAGNETICMICROBEADS • Localization of therapeutic agent • Bioengineering & biomedical trends like enzyme immobilization, protein purification, cell isolation • DNA analysis • Drug discovery • Molecular targeting
- 22. PREPARATION OF MICROSPHERES METHOD DESCRIPTION APPLICATION Emulsion solvent evaporation Drug+polymer sol=>to aqueous phase(PVP) = EMULSION(O/W) =>evaporate solvent = microsphere •Aceclofenac microspheres •Hollow microspheres Emulsion cross linking Drug=+Gelatin sol=>add drops to liquid paraffin=emulsion(W/O)=>MIC ROBEADS washed with isopropyl alcohol=>add to glutaraldehyde sol Gelatin A microspheres
- 23. PREPARATION OF MICROSPHERES METHOD DESCRIPTION APPLICATION Co-acervation Drug+Polymer sol=>phase separation -change in T,pH -salt or non solvent addition •Proteins •Steroids Emulsion-solvent diffusion Drug polymer mix+ethanol:dichloromethane (1:1)=>add dropwise to SLS sol=agitate at 40C => microbeads dried Microballons Ionic gelation Diclofenac sodium+ sodium alginate aq sol=>add to Ca2+ & chitosan sol in acetic acid = microsphere kept for 24 hrs for internal gellification Diclofenac sodium=> drug release at pH6.4-7.2
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- 25. NANOPARTICLES • 1-100nanometer in size • Also called ULTRAFINE PARTICLES • NANOTECHNOLOGY defines particle as a small object that behaves as a whole unit with respect to its transport and properties
- 26. PROPERTIES • Highsurface area- volume ratio • Act as bridge between bulk materials and atomic/molecular structures • Size dependent properties are observed • Possess unexpected optical properties as they are small enough to confine their electrons and produce quantum effects
- 27. TYPES OF NANOPARTICLES NANO-CARRIER DESCRIPTION IMAGE APPLICATION NANO SHELLS Hollow silica spheres covered with gold Targeting tumor cells NANO WIRES Metallic:Au,Ni Semi conducting:Si, InP Insulating:SiO2 Detect tumor in brain,treatment of Parkinson's
- 28. TYPES OF NANOPARTICLES QUANTAM DOTS Miniscule semiconductor particles Targeting cancerous cells GOLD NANOPARTICL ES Ultra sensitive detection system for DNA& proteins Genetic engineering DENDRIMERS Synthetic nanoparticle ,510nm diameter Medical imaging, gene transfection
- 29. PREPARATION OF NANOPARTICLES • TOP DOWN Attrition : broad size distribution (10-1000 nm) : varied particle shape or geometry : impurities • BOTTOMS UP METHODS o Vapor phase fabrication: pyrolysis o Liquid phase fabrication: sol gel method
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- 31. Marketed drugs BRANDGENERIC NAME INDICATION COMPANY Tricor® Fenofibrate Hypercholesterol emia Abbott Laboratories Avinza® Morphine sulphate Psycho stimulant Elan nano systems Rapamune® Rapamycin immunosuppresa nt Elan nano systems