Magnetic field controlled smart polymer

for controlled drug deliveryBy:

Labeesh Kumar

Pankaj Jain

2Introduction

polymers

for CDD

Core–shell nano-

partical carrier

CDD behaviour

PEG magnetite

nanoparticles

• Magnetic field responsive material shows change in their physical properties in an external magnetic field.

• Stimuli-responsive material offer a platform that utilised to deliver drugs at a controlled rate and in a stable biologically active form.

Why controlled drug delivery (CDD)..?

• “Intelligent” delivery systems- Release entrapped drugs at the appropriate time and site of action, in response to specific physiological triggers.

4

a)No magnetic field is applied,

b)Non-uniform magnetic field is created by a permanent

magnet,

c)Homogeneous magnetic field.

5Magnetic-field-sensitive gel: as an

artificial muscle…?

Can be understand by influence of

uniform and nonuniform magnetic

fields on gel beads

Field Sensitive Gels

External Field

2 Types of interactions are possible Due to

MAPField –particle interaction

Particle–particle interaction

More in Non-

Uniform field

More in Uniform

field

Field gradient absent No attractive or repulsive field

particle interaction magnetic dipoles.

Magnetophoretic

(MAP) force

fMAP

= 2π μ1

R^3K ▼H^2

MAP force is experienced by particles Due to crosslinking, MAP can lead to

macroscopic shape changes and/or motions

Magnetic drug-targeting carrier

encapsulated with

Thermosensitive smart polymer:

Encapsulation

Carrier

Thermosensitive

polymer

Functionalized nano

magnetite (Fe3O4) &

conjugated anticancer

Therapeutic drug

doxorubicin (DOX)

[Dextran-g-

poly(NIPAAm-co-

DMAAm)].

Magnetite nanoparticles functionalized

by 3-mercaptopropionic acid

hydrazide (HSCH2CH2CONHNH2)

via Fe–S covalent bond.

volume and shape of NIPAAm

change in a reversible manner in

response to small changes in

temperature around the LCST (lower critical solution temperature)

DOX-loading efficiency (%)= 100(Wfeed DOX – Wfree DOX) / Wfeed DOX

The DOX-loading efficiency 89%.

Cumulative doxorubicin release

(%) from the capsulated carrier at room temperature (20 ̊̊̊̊̊̊̊̊̊C)

(<LCST),

physiological temperature (37 ̊̊̊̊̊̊̊̊̊C) (LCST) and

Hyperthermal temperature

(40 ̊̊̊̊̊̊̊̊̊C) (>LCST)

in PBS(Phosphate Buffered

solution), ph 7.4 and 5.3.

• The acidic medium favours drug release because of the

acid-labile linker (hydrozone linkage).

• Enables drug release controlling through small changes

of temperature in the vicinity of LCST and pH.

• The drug release at pH 5.3 was marginally greater than

at pH 7.4.

Poly ethylene glycol functionlazied

magnetic nano particles

• Orally administered anticancer drugs or injections suffer

from the drawback of limited control on the rate of drug

release in addition to harmful side effects and toxicity.

• The preferred regime of that is an initially high release of

drug, followed by a gradual decrease with time.

• This can be achieve by conjugating a drug with a polymer.

the polymer must be bio-degradable.

• The particles are injected into the body, and they are

transported to the region of interest via blood circulation.

there must be two things to be taken into consideration.

(a) The magnetic particles should not aggregate,

(b) When the particles are injected into the bloodstream

they are rapidly coated with circulation components, such

as plasma proteins.

• Firstly we will synthesis magnetic nano particles.

• Purification of nanoparticles was done to prevent

agglomeration. For this the black precipitate was re-

dispersed in hexane in the presence of oleic acid .

• Then the nano particles are functionalized with PEG.

Biphenyl etheriron (III) acetylacetonate dodecanediolOleic acidOleylamine

Mixed thoroughly with a magnetic stirrer, heated up to 2000C in nitrogen atmosphere for 2h Dark black colour solution

obtained which is a indication of obtaining nano

particles

Cooled at room temp. and then methanol is added

Black precipitate obtained

Synthesis of polymer coated magnetic nanoparticles

• The surface of the nanoparticles is modified with folic acid to

promote the internalization so it can readily take up by cells.

• The reactivity of folic acid with polymer is weak so carboxyl

group of folic acid was first activated with dicyclohexyl

carbodiimide (DCC) and dimethyl sulfoxide (DMSO).

Cont…..

Cont…..

• In last step Conjugation of drug to functionalize magnetic

nanoparticles is done to perform this The anticancer drug doxorubicin

was dissolved in tris (hydroxymethyl) aminomethane buffer solution

at pH 7. Folic acid-modified, PEG-encapsulated magnetite

nanoparticles was mixed with drug solution (drug concentration =1

mg ml 1) at pH 7 and stirred at room temperature.

• The coercivity property of a magnetic particle which is

related to resistance to change its magnetic property have a

strong dependency on the particle size.

• The result obtained from FTIR show that general magnetic

behaviour is not altered by encapsulation with the

hydrophilic polymer. The magnetic nanoparticles retained

the super paramagnetic character and the magnetic field

strength.

x 100

Characterization of properties

• Drug loading capacity of the nano particles is measured in a Sephadex G-25 column with the help of UV spectroscopy.

percentage drug loading = [(W1-W2)/W1] x 100

• Drug release capacity from the drug-conjugated nanoparticles is measured by placing them in a porous dialysis membrane and the drug was released into 15 ml of sterilized water at room temperature. And the concentration of drug release is measured by UV spectrophotometer.

percentage drug release = [(W1-W2)/W1] x100

• The initial stage is characterized by a rapid release of drug This

initial stage is followed by a slow, steady and controlled release of

drug

• The second stage signifies that the drug release is nearly constant

with time. Based on the drug delivery response.

S. Rana, R.S. Srivastava, R.D.K. Misra; on the chemical synthesis and

drug delivery response of folate receptor-activated, polyethylene

glycol-functionalized magnetite nanoparticles; Acta Materialia Inc.; 4

(2008). 40–48;

M.Zrinyi, Dept. of physical Chemistry TechnicalUniversityof

Budapest H-152 ; Intelligent polymer gels controlled by magnetic

fields; Colloid Polym Sci 278:98-103 (2000)

Honey Priya James, Rijo John, Anju Alex, Anoop K.R; Smart

polymers for the controlled delivery of drugs – a concise overview ;

2211-3835 & 2014;Acta Pharmaceutica Sinica B

R.D.K. Misra, J.L. Zhang; Magnetic drug-targeting carrier

encapsulated with thermosensitive smart polymer: Core–shell

nanoparticle carrier and drug release response; Acta Biomaterialia 3

(2007) 838–850

Shinkai M.;Functional magnetic particles for medical application; J

Biosci Bioeng 2002;94:606

Thanks !

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