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  • 1. NANOMAGNETOSOL S BY T.VENKATESH M.PHARMACY PHARMACEUTICS Sri Kakatiya Institute of Pharmaceutical Sciences HANAMKONDA, WARANGAL.506001.
  • 2. CONTENTS  Introduction.  Properties Of Magnetic Materials Of Purpose.  Advantages and Disadvantages of Nanomagnetosols.  Recent Applications of Nanomagnetosols.  Conclusion.  References.
  • 3. INTRODUCTION  A drug or therapeutic radionuclide is bound to or co-incorporated along with magnetic compound and introduced in to human body, then concentrated in the target area by means of a magnetic field (using an internally implanted permanent magnet or an externally applied field) is called as magnetic drug delivery.  Drug release can proceed by simple diffusion or take place through mechanisms requiring enzymatic activity or changes in physiological conditions such as pH, osmolality, or temperature. Drug release can also be magnetically triggered from the drugconjugated magnetic nanoparticles.  Magnetic targeting is of active targeting with the application of physical force(magnetic force).
  • 4.  The magnetic nanoparticles can be used for hyperthermia applications, due to the heat they produce in an alternating magnetic field The resulting temperature increase can be used to modify or inhibit specific cell activities locally, or even to release drugs in a precisely controlled, temperature-increase activated manner.  Magnetic nanoparticles can also serve as contrast agents for diagnostic applications such as magnetic resonance imaging.  Magnetic nanoparticles possess many characteristics that make them promising as drug carriers and for use in biomedical applications.
  • 5.  Few of biochemical applications are summarized as below  The accumulation of magnetic nanoparticles can be used on its own to starve the target tissue of oxygen, produce hypoxia and induce necrosis in tumor cells (Gkiozos I et al ., 2007).
  • 6.  With respect to lung disease, aerosol delivery of drugs by inhalation represents the most straight forward strategy for targeting the diseased tissue (Patton JS et al., 2005).This approach of ‘targeted dose intensification’ for human lung cancer therapy has been attempted in only a few previous studies.  Dames et al. in their study have brought aerosol delivery to an advanced level of specificity by using magnetism to direct magnetizable aerosol droplets specifically to desired regions of the lungs.  To date, magnetic drug targeting has been explored mostly in pre-clinical models for cancer therapy with intravascular administration of ‘magnetic’ drug formulations.
  • 7.  A schematic presentation of the concept of magnetic drug targeting to tumor tissue on intravascular administration is shown below. Magnetic drug targeting with intravascular administration
  • 8.  ‘Nanomagnetosols’, as Dames et al. call their compositions for magnetic drug targeting via the airways, can be generated easily with state-of-the-art nebulizers that are in clinical use and contain an appropriate quantity of iron oxide nanoparticles. These make them susceptible to magnetic field guidance. Targeted delivery of magnetic aerosol droplets
  • 9.  The nanomagnetosol approach might allow more-specific targeting of diseased lung areas not only in cancer but also in the case of infectious lung diseases (Sharma S et al., 2001) .  The fact that plasmid DNA can be magnetically targeted to specific regions of the lung via nanomagnetosols generates an interesting link to a method known as ‘magnetofection’, (Plank C et al., 2005) is a method of magnetic drug targeting applied to nucleic acids. This would be an exciting extension to the current options for In vivo gene delivery.  The amount of magnetic nanoparticles per aerosol droplet that would be required to deflect nanomagnetosols sufficiently by ‘reasonable’ magnetic force in the force-field of an aerosol stream under the constraints of lung anatomy. ‘Reasonable’ means that such fields can be generated with affordable equipment with field strengths that are compatible with clinical application.
  • 10. PROPERTIES OF MAGNETIC MATERIALS OF PURPOSE.  Superparamagnetic , ferro- and ferri magnetic particles.   Should be deflected in low magnetic field application. Appropriate surface chemistries and functionalizations is also important.  High thermal energy.  Non bio-interactive.  Biocompatible.  Nontoxic.
  • 11. MAGNETIC MATERIALS IN USE  Iron oxide based magnetic nanoparticles 1) superparamagnetic magnetite (Fe304) 2) maghemite (Fe203). less deflection to magnetic strength at low magnetic field applications  Cobalt based magnetic nanoparticles toxicity  Iron based magnetic particles sensitivity to oxidation
  • 12. ADVANTAGES  Overcomes the natural deposition mechanism of inhaled aerosol droplets in the lungs that only allows targeting of the central airways or lung periphery but not local regions in the lungs.  Offer a degree of flexibility in terms of magnetic drug formulation that has not previously been possible.  Co-incorporation into aerosol droplets without further physical association between the drug and nanoparticle.  Achieved improvements (magnetofection) in nucleic acid delivery.
  • 13.  Similar pharmokinetics as would be seen for the drug or gene vector on its own can be expected.  Used as versatile tools.  Because the magnetic force acting on a magnetic particle is proportional to the third power of its radius, packaging a multitude of magnetic nanoparticles in a larger carrier, such as an aerosol droplet, greatly improves magnetic guidability Dames et al.  low side effects , low dosing of drug.
  • 14. DISADVANTAGES  Generating sufficient magnetic flux density and field gradient at the target site, which will be at a distance of at least several centimeters from the source of the field (e.g. a pole tip)  Even in the presence of higher magnetic force nanomagnetosols penetration in to deeper lung tissues is limited by inertia for inhalation nanoparticles.  Exerting sufficient magnetic force on magnetic nanocarriers to counterbalance hydrodynamic forces has been one of the major limitations in magnetic drug targeting with intravascular administration to date.
  • 15.  Particles below 500nm of MMAD are exhaled out (Ally, J. et al., 2006) .  Iron oxide related toxicity  Accumulation of red blood cells on higher magnetic field application.  Formation of magnetic agglomerates in case of ferri and ferro magnetic nanoparticles.
  • 16. RECENT APPLICATIONS  Rudolph C et al., (2005) investigated a novel method which brings aerosol delivery to an advanced level of specificity by making use of magnetic gradient fields to direct magnetizable superparamagnetic iron aerosol oxide droplets containing nanoparticles (SPION) specifically to desired regions of the lungs in mice.  To target the effected region of cancerous lung in mice Rudolph C et al., (2005) two independent methods used to increase and localize aerosol deposition.  SPIONs nebulized through intratracheal aerosol device and whole-body aerosol device.
  • 17. Representation of the whole-body aerosol device. (a) A plastic box which houses the mice is connected to the nebulizer via an aerosol spacer placed in horizontal orientation. The detailed dimensions of the aerosol device are described in Rudolph et al. . (b) To avoid the mice from adhering together with their magnets, six small chambers of equal size are inserted into the box made from a fine non-magnetic mesh. The mesh size should allow unrestricted aerosol flow.
  • 18. Schematic representation of the FlexiVent respirator(intra tracheal aerosol device) system used for ventilation and aerosol application.
  • 19. Fixation of a permanent magnet above the thorax of a mouse. The permanent magnet is fixed on the fur covering the thorax of the mice by using either tissue glue or any other instant adhesive.
  • 20. CONCLUSION  Magnetic targeting of aerosol streams comprising active agents could, at the very least, become a valuable research tool. In the best case scenario, nanomagnetosols might be generated entirely from only three clinically approved components: approved drugs, approved magnetic nanoparticles and water or saline. This should greatly accelerate product development.
  • 21. REFERENCES  Rudolph C et al. Magnetic aerosol targeting of nanoparticles to cancer: NANOMAGNETOSOLS. Methods Mol Bio. 2010, 624:267-280.  Dames P et al. Targeted delivery of magnetic aerosol droplets to the lung. Nat. Nano. 2007, 2, 495–499.  Plank C et al. Localized nucleic acid delivery: a discussion of selected methods. In DNA Pharmaceuticals,2005, pp. 55–116.  Sharma S et al. Development of inhalational agents for oncologic use. J. Clin. Oncol. 2001, 19, 1839–1847.  Ally, J. et al. Factors affecting magnetic retention of particles in the upper airways: an in vitro and ex vivo study. J. Aerosol Med. 2006, 19, 491–509
  • 22.  Safarik I et al. Use of magnetic techniques for isolation of cells. J.Chromatography .1999, B 772:33-53.  Gkiozos I et al. Developments in the treatment of non-small cell lung cancer. Anticancer Res . 2007, 27(4C), 2823–2827.  Patton JS et al. The lungs as a portal of entry for systemic drug delivery. Proc. Am. Thorac. Soc. 2004, 1, 338–344.  Ferrari M.et al. Applications of magnetic nanoparticles. Nat. Rev. Cancer (2005) 5, 161.  Cunningham CH et al. Magnetic resonance imaging. Magn. Reson. Med. (2005) 53, 999.
  • 23. IF BEING FEASIBLE IS THE ONLY OPTION OF LIFE, THEN THERE IS NO ‘NO’ FOR ANY WORK. BUT BEING FEASIBLE IS ATYPICAL.