Drug delivery and nanomedicine with nanomagnetic material


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Drug delivery and nanomedicine with nanomagnetic material

  1. 1. Drug Delivery and Nanomedicine with Nanomagnetic Material Course: Nanomagnetic Materials and Device Code: NAST-736 Presented By, S.Shashank Chetty 2nd Year, M.Tech, NAST
  2. 2. Outline Biomagnetism Advantages and application of Magnetic material Schematic illustration of MNP-based therapies. Special Features of Magnetic Nanoparticles. Synthesis and biofunctionalisation of magnetic nanoparticles. Modified Nanoparticle and tissue interaction. Size Dependence On Particle removal and particle delivery Magnetic separation and drug carrier. Hyperthermia therapy Conclusion Reference
  3. 3. INTRODUCTION • Magnetism and magnetic materials have been used for many decades in many modern medical applications. • Magnetic materials - cell separation, immunoassay, magnetic resonance imaging (MRI), drug and gene delivery, minimally invasive surgery, radionuclide therapy, hyperthermia and artificial muscle applications. • Physical properties which make magnetic materials attractive for biomedical applications are, • first, that they can be manipulated by an external magnetic field – this feature is useful for separation, immunoassay and drug targeting, and • second, hysteresis and other losses occur in alternating magnetic fields – this is useful in hyperthermia applications. • In biology, bees and pigeons of magnetic materials as biological compasses for navigation. Some magnetotactic bacteria are known to respond to a magnetic field. • The earliest known biomedical use of naturally occurring magnetic materials involves magnetite (Fe3O4) or lodestone which was used by the Indian surgeon Sucruta around 2,600 years ago.
  4. 4. • Biomagnetism - In the human body, there is a constant movement of ions within and outside the cells as well as across cellular membranes. This electrical activity is responsible for magnetic fields, called biomagnetic fields, which we can measure using sensitive instruments placed outside the body. Fig. Schematic depicting the spin magnetic moments for Fe3+ and Fe2+in Fe3O4 Magnetism and Magnetic Materials Categories of Magnetic Materials The Influence of Temperature
  5. 5. The main advantages of magnetic (organic or inorganic) NPs are that they can be: (i) visualized (superparamagnetic NPs are used in MRI); (ii) guided or held in place by means of a magnetic field; and (iii) heated in a magnetic field to trigger drug release or to produce hyperthermia/ablation of tissue.
  6. 6. Fig: Schematic illustration of MNP-based cancer therapies.
  7. 7. Magnetic properties of such materials enable their applications in numerous areas • Magnetically responsive nano- and microparticles and other relevant materials can be selectively separated (removed) from the complex samples using an external magnetic field (e.g. using an appropriate magnetic separator, permanent magnet, or electromagnet) – Magnetic separation • This process is very important for bioapplications due to the fact that absolute majority of biological materials have diamagnetic properties which enable efficient selective separation of magnetic materials. • Magnetic particles can be targeted to the desired place and kept there using an external magnetic field. These properties can be used e.g. for sealing the rotating objects or in the course of magnetic drug targeting. • Magnetic particles can generate heat when subjected to high frequency alternating magnetic field; this phenomenon is employed especially during magnetic fluid hyperthermia (e.g., for cancer treatment).
  8. 8. • Magnetic iron oxides nanoparticles generate a negative T2 contrast during magnetic resonance imaging thus serving as efficient contrast agents. • Magnetorheological fluids exhibit great increase of apparent viscosity when subjected to a magnetic field. • Magnetic nano- and microparticles can be used for magnetic modification of diamagnetic biological materials (e.g. cells or plant-derived materials), organic polymers and inorganic materials, and for magnetic labeling of biologically active compounds (e.g. antibodies, enzymes, aptamers etc.). • Magnetic Particles: Exhibiting magnétisation on exposure to magnetic Field. • Magnetic Twisting: Twisting the magnetically tagging Biomolecules under magnetic field. • Magnetic Tweezer: Fetching the magnetically tagged Biomelecules under magnetic field • Magnetuc clustering: Clustering the Magnetically tagged Biomeolecule under Magnetic field.
  9. 9. Size Dependent Magnetism Fig. Magnetic properties are affected by the particle size (DM = diamagnetic, PM = paramagnetic, SPM = superparamagnetic, FM = ferromagnetic) Types of BioMagnetic Application
  10. 10. Special Features of Magnetic Nanoparticles Figure 1. The different magnetic effects occurring in magnetic nanoparticles. The spin arrangement in a) a ferromagnet (FM) and b) an antiferromagnet (AFM); D=diameter, Dc=critical diameter. c) A combination of two different ferromagnetic phases (magenta arrows and black arrows in (a)) may be used for the creation of novel functional nanomaterials, for example, permanent magnets, which are materials with high remanence magnetization (Mr) and high coercivity (HC), as shown schematically in the magnetization curve (c), d) An illustration of the magnetic moments in a superparamagnet (SPM). A superparamagnet is defined as an assembly of giant magnetic moments which are not interacting, and which can fluctuate when the thermal energy, kBT, is larger than the anisotropy energy. Superparamagnetic particles exhibit no remanence or coercivity, that is, there is no hysteresis in the magnetization curve (d). e) The interaction (exchange coupling; linked red dots) at the interface between a ferromagnet and an antiferromagnet produces the exchange bias effect. In an exchange-biased system, the hysteresis is shifted along the field axis (exchange bias field (Heb))and the coercivity increases substantially. f) Pure antiferromagnetic nanoparticles could exhibit superparamagnetic relaxation as well as a net magnetization arising from uncompensated surface spins (blue arrows in (b)). This Figure, is a rather simplistic view of some phenomena present in small magnetic particles. In reality, a competition between the various effects will establish the overall magnetic behavior.
  11. 11. Modified Nanoparticle and tissue interaction
  12. 12. Examples and Property Requirements of Magnetic Biomaterials • Magnetite is found in many biological entities, from bacteria to people. It is an example of cubic ferrites which have an inverse spinel structure. It is ferrimagnetic with a Curie temperatureof 578 ◦C and a saturation magnetization of 4.76 × 105 A/m. • Another example is maghemite (gamma Fe2O3), which is formed when magnetite is oxidized. It has a structure similar to that of magnetite, the difference being that all or most of the iron is trivalent, the saturation magnetization is 4.26 × 105 A/m. • Ferritin is a protein that stores iron in humans. It contains typically 4,500 iron atoms in an approximately spherical 12 nm diameter molecule. It has a 12 subunit protein shell containing a ferrihydrite core and an antiferromagnetic core. • Gadolinium(III) chelates are commonly used in MRI applications. • Iron coated with activated carbon has recently been tried for magnetic drug targeting for the treatment of hepatocellular carcinomas.
  13. 13. • The magnetic biomaterial can, in principle, also be Ni, Co, b.c.c. Fe, magnetic alloys of Fe, Co, Ni, Nd–Fe–B or samarium–cobalt materials. • In all cases, however, issues of biocompatibility and toxicity limit the choice of materials; however, the use of coatings may make the use of these materials feasible. • The hard magnetic materials Nd–Fe–B and samarium–cobalt have the disadvantage that large external fields are required to influence these materials. • Materials with high magnetization and high susceptibility are preferred for applications such as drug targeting and magnetic separation. • Most of the examples of useful magnetic biomaterials are in powder form, and usually the particles are suitably coated before use. • Ideally, the magnetic material should be non-toxic and non-immunogenic.
  14. 14. • In the case of drug delivery, the particle sizes should be small enough to be injected into the bloodstream and then to pass through the required capillary systems. • In many cases, it is required to coat the magnetic particles; this is usually done by coating with a biocompatible polymer or with other coatings such as gold, activated carbon or silica. • The coating reduces aggregation and prevents the magnetic particle from being exposed directly to the body. • In addition, the polymer can be used as a matrix in which drugs, radionuclides or genetic material can be dissolved or as a site for binding of drugs; thus the magnet-coating system can act as “carrier” to deliver useful material to the targeted region. • Some examples of common coatings are derivatives of dextran, polyethylene glycol (PEG) and polyethylene oxide (PEO), phospholipids and polyvinyl alcohol
  15. 15. Synthesis of Magnetic Nanoparticle and biofunctionalisation
  16. 16. Fig. Magnetic carrier for drug targeting and drug delivery Fig: Interaction within the functionalized Nanoparticle
  17. 17. Size Dependence On Particle removal and particle delivery
  18. 18. • Cell labelling and magnetic separation- It is a two-step process, involving (i) the tagging or labelling of the desired biological entity with magnetic material, and (ii) the separating out of these tagged entities via a fluid-based magnetic separation device. Magnetic separation
  19. 19. • Tagging is made possible through chemical modification of the surface of the magnetic nanoparticles, usually by coating with biocompatible molecules such as dextran, polyvinyl alcohol (PVA) and phosopholipids—all of which have been used on iron oxide nanoparticles. • As well as providing a link between the particle and the target site on a cell or molecule, coating has the advantage of increasing the colloidal stability of the magnetic fluid. • Specific binding sites on the surface of cells are targeted by antibodies or other biological macromolecules such as hormones or folic acid. • As antibodies specifically bind to their matching antigen this provides a highly accurate way to label cells. • For example, magnetic particles coated with immunospecific agents have been successfully bound to red blood cells, lung cancer cells, bacteria, urological cancer cells and Golgi vesicles. • For larger entities such as the cells, both magnetic nanoparticles and larger particles can be used: for example, some applications use magnetic ‘microspheres’— micron sized agglomerations of sub-micron sized magnetic particles incorporated in a polymeric binder • This force needs to overcome the hydrodynamic drag force acting on the magnetic particle in the flowing solution, Fd = 6πηRm ∆v, where η is the viscosity of the medium surrounding the cell (e.g. water), Rm is the radius of the magnetic particle, and v = vm −vw is the difference in velocities of the cell and the water
  20. 20. • The major disadvantage of most chemotherapies is that they are relatively non-specific. • The therapeutic drugs are administered intravenously leading to general systemic distribution, resulting in deleterious side-effects as the drug attacks normal, healthy cells in addition to the target tumour cells. • The objectives are two-fold: (i) to reduce the amount of systemic distribution of the cytotoxic drug, thus reducing the associated side-effects; and (ii) to reduce the dosage required by more efficient, localized targeting of the drug Magnetic drug carriers
  21. 21. Hypertherm ia of heat generated per unit volume is • The amount given by the frequency multiplied by the area of the hysteresis loop: PFM = μ0f ∫H dM.
  23. 23. Conclusion • Advancements in our ability to fabricate MNPs with greater control over physicochemical and bioactive properties have led to new NP candidates for imaging and therapeutic use. • These formulations offer • (1) disease diagnosis at their earliest stages and improved preoperative staging, • (2) delivery of therapeutics specifically to diseased tissue, limiting unwanted side effects, and • (3) non-invasive monitoring capabilities of new therapeutics. Size, shape, and surface chemistry dictate in vivo behavior, including biodistribution, biocompatibility, and pharmacokinetics. • As such, these parameters can be tuned to achieve enhanced targeting via passive, active, and magnetic targeting mechanisms. • Active targeting, in particular, offers high sensitivity due to the ability to direct MNP localization, but requires added attention be paid to the targeting agent used, and the method of MNP attachment employed. • A number of bioconjugation strategies including physical methods, covalent strategies, and click chemistries are available, each having distinct advantages. • In addition to assisting in disease imaging, cell targeting by MNPs can also assist in disease treatment if a therapeutic payload is integrated into the MNP. • This requires additional design considerations, though, including type of therapeutic, method of release, and intracellular activity.
  24. 24. Reference • Chapter 17, Magnetic Particles for Biomedical Applications by Raju V. Ramanujan. • O. Veiseh, et al., Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging, Advanced Drug Delivery Reviews (2009). • Q A Pankhurst et al., Applications of magnetic nanoparticles in biomedicine, J. Phys. D: Appl. Phys. 36 (2003) R167–R181. • T.K Indira and P.K Lakshmi, Magnetic Nanoparticle- A review, International Journal of Pharmaceutical science and nanotechnology, 3, 3 (2010). • F. Schth et al., Magnetic Nanoparticles: Synthesis, Protection, Functionalization, and Application, Angew. Chem. Int. Ed. 2007, 46, 1222 – 1244. • Akbarzadeh et al., Magnetic nanoparticles: preparation, physical properties, and applications in biomedicine, Nanoscale Research Letters 2012, 7:144 • Nhiem Trana and Thomas J. Webster, Magnetic nanoparticles: biomedical applications and challenges, J. Mater. Chem., 2010, 20, 8760–8767. • Jaromir Hubaleket al., Magnetic nanoparticles and targeted drug delivering, Pharmacological Research 62 (2010) 144–149. • Gao Songet al., Magnetic nanoparticle-based cancer therapy, Chin. Phys. B Vol. 22, No. 2 (2013) 027506.
  25. 25. • Sheng Tonget al., Multifunctional Nanoparticles for Drug Delivery and Molecular Imaging, Annu. Rev. Biomed. Eng. 2013. 15:253–82. • Kuo-Chen Wei et al., Potential of magnetic nanoparticles for targeted drug delivery, Nanotechnology, Science and Applications 2012:5 73–86 • Akira Yoshiasa et al., Synthesis of novel CoCx@C nanoparticles, Nanotechnology 24 (2013) 045602. • Carlos J Serna et al., The preparation of magnetic nanoparticles for applications in biomedicine, J. Phys. D: Appl. Phys. 36 (2003) R182–R197. • Chapter 7, Magnetic Nanoparticles: Synthesis, Surface Modifications and Application in Drug Delivery by Seyda Bucak, Banu Yavuztürk and Ali Demir Sezer. • Article in Nanotoday, Magnetic nanoparticles for drug delivery, JUNE 2007 | VOLUME 2 | NUMBER 3