Magnetic field control drug delievery
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Transcript of Magnetic field control drug delievery
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
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