MAGNETIC MICROSPHERES           Prepared By:              Sonam M. Gandhi                                1
DEFINITION:                   Magnetic micro carriers aresupramolecular particles that are small enough to circulatethroug...
Advantages:1. Therapeutic responses in target organs occurs   at only one tenth of free drug dose.2. Controlled drug relea...
Disadvantages:1. Magnetic targeting is an expensive, technical approach and    requires specialized manufacture and qualit...
Concept of targeting magnetic microspheres:Microspheres containing magnetic material (magnetite)are injected into an arte...
To localize microspheres in a fast moving arterialsystem, greater field strength is required.When the microspheres are ...
Important characteristics: In targeting using magnetic microspheres, the  magnetite content of carrier and also magnitude...
 Drug incorporation and magnetite has to  be delicately balanced. Optimum magnetite content would be  between 20%-50% of...
Magnetite:A ferromagnetic material when incorporated intomicrospheres makes them magnetically responsive So thatthey can ...
Super paramagnetic particlesunder the influence of an externalmagnetic field Super paramagnetic particles in absence of an...
Magnetic guidance:Initially drugs were grafted on to the surface ofthe magnetic particles, but it suffers from thedrawbac...
PREPARATION OF MAGNETICMICROSPHERES•Magnetically responsive microspheres can beprepared by using albumin as a carrier of d...
CONTINUOUS SOLVENT EVAPORATION      Solution in volatile organic solvent        (polymer + drug + magnet)               Au...
PHASE SEPARATION EMULSION POLYMERIZATION     Aqueous solution              Vegetable oil (albumin+drug+magnetite)         ...
Assembly used for separation of magneticmicrosphere from non magnetic materials                                           15
Evaluation of drug release rate in vitro1. Dialysis method2. Continuous column elution method                             ...
a. Dialysis methods:Albumin microspheres were taken in a funnel, 3mlof phosphate buffer of 7.3 pH was added.The mouth of...
b.Continuous column elution methods:Microspheres are immobilized on a columncontaining a fixed weight of glass wool (3.5 g...
Characterization:Carrier localization: gamma cameraimaging; high frequency ultrasound;magnetic resonance technique        ...
SEM - scanning electron microscopy                                     20
In vivo drug distribution: magneticresonance imaging                                      21
Microspheres localization: Ultrasoundtechniques                                        22
Particle size and shape: SEM                               23
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Magnetic microspheres

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Magnetic microspheres

  1. 1. MAGNETIC MICROSPHERES Prepared By: Sonam M. Gandhi 1
  2. 2. DEFINITION: Magnetic micro carriers aresupramolecular particles that are small enough to circulatethrough capillaries without producing embolic occlusion(<4µm) but are sufficiently susceptible (ferromagnetic) tobecome captured in micro vessel and dragged into theadjacent tissues by magnetic fields of 0.5 to 0.8 tesla (T). 2
  3. 3. Advantages:1. Therapeutic responses in target organs occurs at only one tenth of free drug dose.2. Controlled drug release within target tissues for intervals of 30 min to 30 hr .3. Avoidance of acute drug toxicity directed against endothelium and normal parenchyma cells.4. Adaptable to any part of the body. 3
  4. 4. Disadvantages:1. Magnetic targeting is an expensive, technical approach and requires specialized manufacture and quality control system.2. It needs specialized magnet for targeting, advanced techniques for monitoring and trained personnel to perform procedures.3. Magnets must have relatively constant gradients, in order to avoid focal over-dosing with toxic drugs.4. A large fraction of the magnetite which is entrapped in carriers is deposited permanently in target tissues.5. Due to these limitations magnetic drug targeting is likely to be approved only for severe diseases. 4
  5. 5. Concept of targeting magnetic microspheres:Microspheres containing magnetic material (magnetite)are injected into an artery that supplies to a given site.As the microspheres would be selectively andmagnetically localized at the capillary level they have freeflow access through large arteries.Thus the microspheres would serve as the time releasecapsules systems sitting in the desired location.A magnet of sufficient field strength is thus placedexternally over the target area to localize the microspheresat the capillary bed in this region. www.themegallery.com LOGO 5
  6. 6. To localize microspheres in a fast moving arterialsystem, greater field strength is required.When the microspheres are first pushed against theendothelial cells by the magnetic field, an endocyticresponse was triggered with continuous magnetic influenceover certain period of time.Microspheres migrated from endothelial cells into theinterstitial compartment and formed a depot for sustainedrelease over an extended period of time. 6
  7. 7. Important characteristics: In targeting using magnetic microspheres, the magnetite content of carrier and also magnitude of applied magnetic field is important. Particle size of drug carrier can affect the degree of drug entrapment. If a high magnetic content is incorporated, thus amount of magnetic fields needed is reduced but the space available for drug entrapment decreases. 7
  8. 8.  Drug incorporation and magnetite has to be delicately balanced. Optimum magnetite content would be between 20%-50% of drug weight in the drug carrier complex. 8
  9. 9. Magnetite:A ferromagnetic material when incorporated intomicrospheres makes them magnetically responsive So thatthey can be concentrated to the desired site by applyingsome magnetic field.Iron is strong ferromagnetic material but due to its localtissue irritation and other toxic manifestation it cannot beincluded into microspheres.But such a problem is not seen when magnetite which ischemically ferrous ferric oxide (Fe3o4) biologicallycompatible and also its ultra fine particle size makes itsuitable material. 9
  10. 10. Super paramagnetic particlesunder the influence of an externalmagnetic field Super paramagnetic particles in absence of an external magnetic field, monodisperse particle 10 distribution
  11. 11. Magnetic guidance:Initially drugs were grafted on to the surface ofthe magnetic particles, but it suffers from thedrawbacks like very low loading capacity andirreversible particle aggregation under theexposure of magnetic field.Coating of the ferromagnetic particles withalbumin and other charged polymers decreases theaggregation problem by making it reversible. 11
  12. 12. PREPARATION OF MAGNETICMICROSPHERES•Magnetically responsive microspheres can beprepared by using albumin as a carrier of drug andmagnetite.•Size of microspheres is kept between 1-2 µm, sothat they can be injected into blood vessels withoutproblem of thrombo -embolism.Two methods are employed for the preparationthey are1. Phase separation emulsion polymerization2. Continuous solvent evaporation 12
  13. 13. CONTINUOUS SOLVENT EVAPORATION Solution in volatile organic solvent (polymer + drug + magnet) Auxillary Solution Stirring Homogenization Stirring temp (22o-30o C) Magnetic Microsphere Separated by centrifugation Freeze drying and storage at 4o C 13
  14. 14. PHASE SEPARATION EMULSION POLYMERIZATION Aqueous solution Vegetable oil (albumin+drug+magnetite) Emulsification Stabilization by Heat Cross linking agent ( 100-150C) Microsphere suspension Separated from oil Freeze drying & storage at 4C 14
  15. 15. Assembly used for separation of magneticmicrosphere from non magnetic materials 15
  16. 16. Evaluation of drug release rate in vitro1. Dialysis method2. Continuous column elution method 16
  17. 17. a. Dialysis methods:Albumin microspheres were taken in a funnel, 3mlof phosphate buffer of 7.3 pH was added.The mouth of the funnel is covered withcellophane paper and fastened with rubber band. Then funnel is inverted into a beaker containing50 ml phosphate buffer. 2.5 ml of aliquots arewithdrawn every half an hour and replaced withfresh buffer and estimated for drug release. 17
  18. 18. b.Continuous column elution methods:Microspheres are immobilized on a columncontaining a fixed weight of glass wool (3.5 gm) as asupport material and kept at 37oC. they aresubjected to a constant flow of 50 ml phosphatebuffer, fractions are collected at equal intervals andamount of drug release is estimated by using UVspectroscopy. 18
  19. 19. Characterization:Carrier localization: gamma cameraimaging; high frequency ultrasound;magnetic resonance technique 19
  20. 20. SEM - scanning electron microscopy 20
  21. 21. In vivo drug distribution: magneticresonance imaging 21
  22. 22. Microspheres localization: Ultrasoundtechniques 22
  23. 23. Particle size and shape: SEM 23

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