Magnetic Nanoparticles Applications

8/12/2019 Magnetic Nanoparticles Applications

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Magnetic NanoparticlesApplications

Dan Laptoiu1, R.Marinescu1,D Popescu2, I.Antoniac21Colentina Clinical HospitalBucharest,2

University Politehnica ofBucharest, Romania
mailto:[email protected]:[email protected]:[email protected]:[email protected]


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What are the Joints?The body would be immobile if not for the movements

afforded by the joints.Joints can be large or small, and permit movements as varied

as walking, bending, reaching, and performing fine motorskills.
http://orthopedics.about.com/library/xrayimages/nllatknee.jpghttp://orthopedics.about.com/library/xrayimages/nllatknee.jpg


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Knee Joint

The knee is the largest joint inthe body, and one of the mosteasily injured.


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Cartilage

Within the joints, the ends of the bones are coveredwith hyalinecartilage.

- cushions the underlying bone against excessive pressureand allows the joint to move easily and without pain.


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Cartilage

damage or injury, it usually goes through a staged process of softening,

flaking, fragmenting, and finally complete loss, where the underlying

bone is exposed.

This process is commonly known as osteoarthritis or OA.


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Synovial Fluid Response to Movement

Fast Impact

ShockAbsorption

Viscosity

Flow

Slow Impact

Elasticity


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Intra-articular Injections

There are two main types of

intra-articular injections.

1. SteroidsInjected into the

joint to decrease inflammation.

2. ViscosupplementationInjected

into the joint to provide lubrication.


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Viscosupplementation

The active ingredient in theinjections is called hyaluronic acid.

There are many preparations ofhyaluronic Acid available; all have

similar properties and none has beenclinically proven more effective.


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What is hyaluronic acid? A long-chain biopolymer with

repeated sequences of N-acetyl-glucosamine and glucuronic acid

Avian / bacterial origin

Hylan:cross-link moleculesmodified from HAs (to increase

viscosity and clearance from thejoint)


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Biologic properties of HA

Lubrication, shock

absorption, viscoelastic

SF

Related to the molar massand concentration

Interaction with pain

receptors

Promotion of endogenousHA

Antiinflammatory properties

Nitrous oxide antagonist

Decr. Prostaglandin production


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How does it last long? 1 day intra-articular sustaining Variable onset of their efficacy

Hyalgan26 wks, Hylan G-F20 52 wks(labeled)

(Raman R The Knee(2008), doi:10.1016/j.knee.2008.02.012)

Inconclusive and controversial for thetherapeutic efficacy

(Adams MEDrug Safety2000;23(2):115-30

Wobig M Clin Ther1999;21:1549-62, Allard S Clin Ther2000;22:792-5)

Need a well designed prospective RCT to resolvethe uncertainty about magnitude of efficacy ofvarious products


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Arthroscopy

Arthroscopy is a day surgery thatis done using instruments and acamera that are placed into thejoint through small holes.


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Arthroscopy on target


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Other targeting methods ?

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Nanotechnology

1021=6000m2


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Outline

How to produce nanomagnets and make thembioavailable

Developing therapies using these bioavailablenanomagnets


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Types of Magnetic particles

Multi domain, single domain orsuperparamagnetic

Magnetite (Fe3O4)Ferrites (MeO . Fe2O3; Me = Ni, Co, Mg, Zn, Mn)

Maghemite (-Fe2O3)

Greigite (Fe3S4)


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Types of Magnets

Ferromagnetic materials=the magneticmoments of neighboring atoms alignresulting in a net magnetic moment.

Paramagnetic materials =randomly orienteddue to Brownian motion, exceptin thepresence of external magnetic field.


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Animal magnetism

Magnetosome chainsfrom the frontal tissuesof chinook salmon

S. Mann et al.:J. Exp. Biol.140(1988) 35-49.


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Magnetotactic bacteria

Various morphological typesexist

Gram-negative prokaryotes

Magnetic nanoparticlespresent in magnetosomes

Found in sediments indiverse aquaticenvironments


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Magnetic nanoparticles

Meteorite magneticnanoparticles resemblemagnetosomes from

Earth magnetotacticbacteria

Hypothesis:Was there atransfer of living

systems from Mars toEarth???


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Superparamagnetic in human

Combination of paramagnetic andferromagnetic properties

Made of nano-sized (~20nm) ferrous

magnetic particles, but affected by BrownianMotion.

They will align in the presence of an externalmagnetic field.

Magnetite naturally found in humanbody.

Hergt, Rudolf. Journal of Physics: Condensed Matter v18 2006 s2919-2934


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Coated Magnetite Nanoparticles

US Patent 5262176

Synthesis of polysaccharide coveredsuperparamagnetic oxide colloids (5,262,176)For MRI imaging

FDA max size for injectables = 220 nm.

Smaller sizes (


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Variation of Formation

Change Coating MaterialVarious other starches, Sulfated Dextran (forfunctionalization)

Crosslinking coating materialIncreases plasma half-life

Same Particle Size


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Application?

Three important bio- Biocompatible (in the broadest sense of this

word)

Biodegradable Biomimetic


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Targeted Use of Nano Magnets

External Magnetic field for nanoparticledelivery

Magnetic nanoparticles loaded with

drug can be directed to diseased site

for Drug Delivery or MRI imaging.

Hergt, Rudolf. J.Physics: Condensed Matter 18 (2006) S2919-S2934

http://www.nist.gov/public_affairs/techbeat/tb2007_0201.htm#magnets


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Magnetic Drug Delivery System

Using Magnetic Nanoparticles for Drug Delivery Widder & others developed method in late 1970s

Drug loaded magnetic nanoparticles introduced through IV orIA injection and directed with External Magnets

Requires smaller dosage because of targeting, resulting in fewerside effects

Pankhurst, et. al. [2003] J PhysD 36:R167-R181.

Dobson [2006]. Drug Dev Res 67:55-60.

Widder, et. al. [1978]. Proc Soc Exp Biol Med 58:141-146.


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Magnetic Nanoparticles/Carriers

Magnetite Core

Starch Polymer Coating Bioavailable

Phosphate in coating for functionalization

Chemo Drug attached to Coating Mitoxantrone

Drug Delivered to Rabbit with Carcinoma

MagnetiteCore

Starch Polymer

M

M

MM

M

MM

R. Jurgons. Journal of Physics: Condensed Matter v 18. (2006) S2893-S2902


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Results of Drug Delivery

External magneticfield (dark)

deliver morenanoparticles to tumor

No magnetic field(white)

most nanoparticles innon tumor regions

R. Jurgons. Journal of Physics: CondensedMatter v 18. (2006) S2893-S2902


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NPS

Dynabeads

Homogeneous sizedistribution

Simple recovery with smallpermanent magnets

Magnetic nanoparticlespresent inside the beads

Available in plain, activated

and bioactive form


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Artromag Project - Synthesis

In a first stage we havesynthesized magnetic particles,which were covered by layer-bylayer method in consecutivelayers of protection (TMOHand IN / SEVEN / CS) and

hyaluronic acid; it is arelatively complex techniquebut very important for theactive biologic properties of thenanoparticles (bothbiocompatibility and quantity

of active substance increased).


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Biofunctionalization

Layer by layer


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NPS samples

No sample CompositionSample 1 (PM + TMOH) + HA

Sample 2 (PM + TMOH + APTEOS) + HA

Sample 3 PM/10 + HA

Sample 4 (PM + TMOH)/10 + HA

Sample 5 (PM + TMOH)/100 + HA

Sample 6 PM/100 + HA

Sample 7 (PM + TMOH + CS) + HASample 8 (PM + TMOH + IN) + HA

Sample 9 PM + HA

Sample 10 HA


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NPS Artromag

Final size of synthesized particles did notexceeded 100 nm (values measured by DLS),are stable and retain their character andmagnetic-polymer composites features

required magnetic nanoparticles to be usedfor its intended purpose.


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FTIR analysis demonstratedthe presence of magnetite andmaghemite in the synthesizedferrofluid, and a polymercoating characteristic groupsusing (3-amino-propyl

trietoxisilan,tetramethylammoniumhydroxide, inulin andhyaluronic acid), whichdemonstrated that thetechnique of embedding in

polymer layers by layer-by-layer method is viable.


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MP+TMOH+IN+HA

relative uniformdistribution around106 nm sizes allowspotentialintraarticular usewithout initialconcern for the

articular remanencestudies havedefined the pore sizefor the cartilagedense collagenmatrix around 60nm.


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Biocompatibility

cytotoxicity test using L929 mouse fibroblasts. The assay meetsthe requirements of international standards (ISO 10993-5,

"Tests for CytotoxicityIn Vitro Methods.


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Permanent magnets


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N38 N40


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Magnet Matrix


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Conclusions

The particles obtained have good sizedistribution, good magnetic qualities andhave no cytotoxicity.

The permanent magnets can manipulate these

particles and maintain them longer inside thejoint, therefore enhancing their qualities.

The results may be promising in TARGETED

therapy for KNEE osteoarthritis .


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QUESTON

How are the clinical results?


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Treatment?

struc ture mod i fy ing treatment


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Thank You!

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Magnetic Nanoparticles Applications