Outline Introduction Synthesis Characteristic of SPIONs Application in drug delivery
Introduction Nanoparticles consist of iron oxidecore Special features1. Supermagnetism2. High field irreversibility3. High saturation field Application in (magnetic resonanceimaging),targeted drug delivery
Synthesis Almost1. Magnetite (Fe3O4 )2. Maghemite (γ-Fe2O3 )3. Hematite (-Fe2O3 ) Rarely mixed oxides of iron andother transition metal ions. 3 most important routes tosynthesis
A comparison of published work (up to date) on the synthesis of SPIONsby three different routes.
Synthesis Sugimoto’s method(Co-precipitation):Preparation by using ferrous salt in the presence ofpotassium hydroxide and potassium nitrate Sol-gel method The most common method reported bymassart:addition of base to an aqueous solution of ferrous andferric ions in a 1:2 stoichiometry andproduction of a black precipitate of sphericalmagnetite NPs of uniform sizes in an oxygen freeenvironment.
Massart’s method VSsugimoto’s method Production oflarger particles(30 to 200 nm) ofrhombic (stirredcondition) andspherical (staticcondition)morphologies insugimoto’smethod
Synthesis Microemulsion :using water droplets asnanoreactor in a continuous phase(oil)in the presence of surfactant molecules. sonochemical routes: formation, growthof nuclei by high energy ultrasonicationIn temperature of 5000 K. Lacks of large scale synthesis
Synthesis Electrochemical deposition under oxidisedconditions(EDOC):oxidizing of anode tometal ion species in the solution. Lacks of large scale synthesis Hydrothermal method: synthesis ofmagnetite by heating of iron precursors inaqueous medium.
Synthesis Biomimetic synthesis by magnetotacticbacteria.
Characteristics of SPIONs(Colloidal stability)SPIONs tend to aggregate!o Controlled by three principle forces Hydrophobic-hydrophilic magnetic(internal) Van derwaalsStabilization in suspension bymodifying their surfaces applieddrug delivery
Characteristics of SPIONs(shape , size and size distribution) Important in biological application Mahmoudi employed multiphysics finiteelement model to study the effects of anapplied magnetic field on SPIONs withvarious sizes in a simulated blood vessel..M. Mahmo udi, M.A. Shokrgozar, A. Simchi, M. Imani, A.S. Milani, P. Stroeve, H. Vali, U.O. Hafeli, S. Bonakdar,Multiphysics ﬂow modeling and in vitro toxicity of iron oxide nanoparticles coated with poly(vinyl alcohol),Journal of Physical Chemistry C 113 (6) (2009) 2322 –2331.
Characteristics of SPIONs(shape , size and size distribution) 2-D geometry andﬁnite element meshmodel of a bloodvessel under apermanent (static)magnetic ﬁeld fordrug delivery.
Characteristics of SPIONs(shape , size and size distribution) The (B) x and (C) y velocitiesof the ferroﬂuid containingSPIONs with various sizes.Results are presented forthe observation point shownin (A). Samples are hereinreferred to as S (x ) M( x ),where S is the stirring rateand M is the NaOH molarity.For instance, S (3600)M(1.2) indicates a sampleprepared with a stirring rateof 3600 rpm and a molarityof 1.2.
Characteristics of SPIONs(shape , size and size distribution) Discussion: Simulation resultssuggest that both the strength of theapplied magnetic ﬁeld and themagnetic properties of SPIONs(which obtained by their various sizeand shapes) affect the velocity ﬁeldﬂuctuations (ﬂow turbulence) andamplitude (peak velocity).
Characteristics of SPIONs(shape , size and size distribution) Conclusion:The velocity ﬁeld with less ﬂuctuationand higher amplitude, especially inthe direction normal to tissue, isbelieved to be preferable to facilitatedrug delivery.
Characteristics of SPIONs(toxicity of SPIONs) Despite potential application of SPIONs, veryfew experiments report their toxicity. Composition toxicity: PVA-coated SPIONstoxicity in all forms,small oxidative DNA lesions,the effect of SPIONs on the cell cycleconﬁrmed the arrest in the G0G1 cell-lifegap.Mahmoudi observed the existence of gasvesicles in SPIONs-treated cells.
Characteristics of SPIONs(toxicity of SPIONs) Protein-nanoparticles interactions: Key issue for defining the toxicity of NPs Cedervall has studied the speciﬁc binding ratesand affinities of different plasma proteins to NPs.Three methods were proposed to study theseinteractions:size-exclusion chromatography (SEC)surface plasmon resonance (SPR)isothermal titration calorimetry (ITC)ITC and SEC allow studying the afﬁnity andstoichiometry of protein bonded to particles, SPRgives the rates of protein association anddissociation.
Characteristics of SPIONs(protein and peptide functionalized SPIONs) In order to increase the targeting capability ofNPs, their surfaces can be conjugated bytargeting species including low-molecular weight ligands (folic acid,thiamine, and sugars), peptides (RGD, LHRD), proteins (transferrin, antibodies, and lectins), polysaccharides (hyaluronic acid)
Characteristics of SPIONs(protein and peptide functionalized SPIONs)
conclusion A comprehensive understanding of thevarious interactions of SPIONs withbiomolecules in the body system (i.e.protein– nanoparticle interactions)would lead to novel SPIONs overcomingthe problem of “rejection of magneticNPs by the human body” “biocompatibility” and “toxicity” in thenear future will be more experimental.
conclusion The ﬁnding of a trace of SPIONs inmitochondria leads to great hope amongresearchers in the ﬁeld for the possibility totreat in the n ear future mitochondrialdisorders and cardiac dysfunctions by usingdrug-loaded particles. It is possible that one day some “intelligentSPIONs ” could be designed to control theaging process.
Thank you for your kind firstname.lastname@example.org 4/26/2013
A particular slide catching your eye?
Clipping is a handy way to collect important slides you want to go back to later.