Magnetically Modulated drug delivery system, Noval Drug Delivery system, New approaches to develop magnetically modulated drug delivery system and Formulation Design.

1. Dr. Zulcaif Ahmad
Ph.D. Scholar (Pharmaceutics)
MPhil Pharmaceutics (Gold Medalist), Pharm.D (Gold Medalist)

2. Magnetically Modulated Drug Delivery
System (MMDDS)
 Drug targeting is the delivery of the drugs to receptors or organs or
any specific part of the body to which one wishes to deliver
exclusively.
 Magnetic Drug Targeting means the specific delivery of therapeutic
agents to their desired target area using magnetic field, e.g. tumors
by using magnetic nanoparticle (ferrofluids) bound to these agents
and an external magnetic field which is focused on the tumor.
 Magnetic fields are believed to be harmless to
biological systems and adaptable to any part of the body.
 Magnetic particles composed of magnetite (rock mineral and one of
the main iron ores, with the chemical formula Fe3O4, Nickle, iron,
cobolt and iron-boron etc) are well tolerated by body.

3. Principles of magnetic targeting
 In this technique, drug is bound to a magnetic compound ,
injected into a patient’s blood stream, and stopped with a
powerful magnetic field in the target area.
 Depending upon the type of drug , it is then slowly released
from the magnetic carriers. Very high concentrations of
chemotherapeutic or radiological agents can be achieved near
the target site ,without any toxic effects to surrounding tissue or
to the whole body.

4. Principles of magnetic targeting
MMDDS
Drug / Carrier
Target Tissue
RES Organs (Liver,
Spleen, Bone marrow)
Mag.Drug/Carrier
Phagocytosis
Target Tissue

5. Mechanism
 Magnetic drug transport technique is based on the fact that the
drug can be either encapsulated into a magnetic microsphere
(or nanosphere) or conjugated on the surface of the
micro/nanosphere.
 When the magnetic carrier is intravenously administered, the
accumulation take place within area to which the magnetic
field is applied.
 An external permanent magnetic field is applied on desired
area to guide and concentrate the drugs.
 Accumulation of the carrier at the target site allows them to
deliver the drug locally.

6. Physiological parameters that affect the MMDDS
 Efficiency of accumulation of magnetic carrier depends on
physiological parameters
 Particle size
 Surface characteristic
 Field strength
 Blood flow rate etc
• This technique give us a major advantage that target the specific
area and reduce the systemic distribution of drugs and result in
effective treatment at lower doses.

7. Concept of Magnetic Drug Targeting
Magnet design: F= M ΔH, F is the force on particles, M is magnetic movement of
particles, ΔH is magnetic field gradient.

8. Magnetically Modulated Microcarriers
 Following are the various magnetic carriers
I. Magnetic microsphere
II. Magnetic liposomes
III. Magnetic nanoparticles
IV. Magnetic Resealed Erythrocytes
V. Magnetic Emulsion
VI. Biomodulators
VII. Magnetic neutrophils

9. I) Magnetic Microsphere
 Magnetic microspheres are supramolecular particles that are
small enough to circulate through capillaries without producing
embolic occlusion (<4 μm)
 The loaded microspheres are introduced into a blood vessel, and
in as little as half an hour, they gather at the target site by
magnetic field of 0.5 – 0.8 tesla (T).
 Magnetic microspheres were prepared by mainly two methods
1. Phase separation emulsion polymerization
2. Continuous solvent evaporation

10. 1) Phase Separation emulsion
Polymerization
Fig 1.1. Formation of Magnetic Microsphere
Dicloromethane
(CH2Cl2) +
Hexadecane
(C16H34)

11. 2) Continuous Phase Evaporation
Fig 1.2. Formation of Magnetic Microsphere

12. Evaluation Parameters
 Particle size analysis
 Surface topography
 Texture
 SEM
 Drug entrapment efficiency
 Percent magnetite content
 In-vitro magnetic responsiveness
 Drug release

13. II) Magnetic liposomes
 Liposomes are simple microscopic vesicles in which lipid bilayer
structures are present with an aqueous volume entirely enclosed
by a membrane, composed of lipid molecule.
 There are a number of components present in liposomes with
phospholipids and cholesterol being the main ingredients but in
case of magneto liposomes magnetite is one of the components
of the liposomes.
Method of Preparation:
 Generally these are magnetic carrier which can be prepared by
entrapment of Ferro fluid within core of liposomes
 Magneto liposome can also be produced by covalent attachment
of ligands to the surface of the vehicles or by incorporation of
target lipids in the matrix of structural phospholipids
 Size range (80to 300 nm)

14. Fig 1.3. Magnetic Liposomes
DOX = Doxorubicin (Anti-cancer drug)

15. III) Magnetic nanoparticles
 Magnetic nanoparticles (MNPs) possess unique magnetic
properties and the ability to function at the cellular and
molecular level of biological interactions making them an
attractive platform.
 MNPs are now being developed for applications in the
detection, diagnosis, and treatment of malignant tumors,
cardiovascular disease, and neurological disease.
Method of Preparation:
 They can be synthesized using different methods like co-
precipitation, thermal decomposition and micro emulsion
method.
 Size range (1 to 100 nm).

16. Co-precipitation
 The simultaneous precipitation of more than one
compound from a solution.
 Reactions involve the simultaneous occurrence of
nucleation, growth, coarsening, and/or agglomeration
processes.
Fig 1.4. Magnetic nanoparticle

17. IV) Magnetic Resealed Erythrocytes
 Erythrocyte load with drug and magnetite using press well technique
 Resealed erythrocytes have various advantages as drug carriers such as it is
a) biodegradable
b) Biocompatible
c) Large quantity of variety of material can be encapsulated within small volume of cell.
d) It can be utilized for organ targeting.
Method of Preparation:
 Magnetic resealed erythrocytes contains ferrofluides (magnetite) along with loaded
drugs (Ibuprofen) within the cell.
 The technique is based upon initial controlled swelling in a hypotonic buffered
solution. This mixture is centrifuged. The supernatant is discarded and the cell
fraction is brought to the lysis point by adding 100-120 liters portions of an aqueous
solution of the drug to be encapsulated. The mixture is centrifuged. The tonicity of
a cell mixture is restored at the lysis point by adding a calculated amount of
hypertonic buffer (also called isotonic treatment).
 Then, the cell suspension is incubated at 37oC to reanneal the resealed erythrocytes.

18. Fig 1.6. Prevention of Arterial
Thrombosis by Aspirin loaded
Magnetic Resealed Erythrocytes.
Fig 1.5. Magnetic resealed erythrocyte formation

19. V) Magnetic Emulsion
 Magnetic emulsion was also tried as drug carrier for
chemotherapeutic agents.
Method of Preparation:
 The emulsion is magnetically responsive oil in water type of
emulsion bearing a chemotherapeutic agent which could be
selectively localized by applying an external magnetic field to
specific target site.
 Akimoto and Morimoto prepared magnetic emulsion by
utilizing ethyl oleate based magnetic fluid as the dispersed
phase, Casein solution as the continuous phase and anticancer
agent, Methyl CCNU (Semustine) trapped in the oily dispersed
phase as an active chemotherapeutic agent.
 Methyl CCNU is a chloroethylnitrosourea

20. Fig 1.7. Magnetic Emulsion

21. VI) Biomodulators
 Biological response modifiers (BMRs) alter host, tumor as well
as microbial responses in four ways
1. Augmentation of host effectors mechanisms directed against
tumor cells or micro organisms.
2. Decrease in host response that interferes with tumor
resistance by a quantitative increase in endogenous effector
resistance by an increase in endogenous effector molecules or
redirecting their sites and duration of action.
3. Augmentation of tumor sensitivity to host cells by
dedifferentiating tumor cells.
4. Increase in host tolerance of conventional cancer treatment.

22.  There are basically two types of agents; Indirect and direct
agents.
 Indirect agents:
 Include white cell chemo attractant, interleukins (1 to 4)
and immunomodulator such as interferon(α , β and γ).
 Direct agents:
 Antibodies, lymphotoxin and tumor necrosis factor (TNF,
also called Cachetin).

23. VII) Magnetic neutrophils
 Indirect approach of targeting white cells by chemo
attraction fails. Even though failure of chemotaxis is not
observed in all patients, such conditions are life
threatening.
 Making neutrophils ingest magnetite base system ought to
be developed, so that the sites of severe infection can be
selectively approached for therapy.

24. APPLICATIONS
 Some of the application of magnetically modulated drug
targeting especially tumor targeting along with some other
application are
1. Magnetic systems for the therapy of diseases.
2. Magnetic delivery of chemotherapeutic drugs to liver tumors.
3. Magnetic targeting of radioactivity.
4. Treatment of tumors with magnetically induced hyperthermia.
5. Other magnetic targeting applications.
6. Magnetic control of pharmacokinetic parameters and drug
release.
 Magnetic systems for the diagnosis of diseases.
 Magnetic systems for magnetic cell separation.

26. CONCLUSION
 Magnetic Drug targeting is efficient & novel approach
of drug targeting.
 Larger amount of freely circulating drug can be
replaced by smaller amount of magnetically targeted
drug.
 It is a challenging area for future research in the drug
targeting.
 More researches, long term toxicity study, and
characterization will ensure the improvement of
magnetic drug delivery system.