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MAGNETIC MICROSPHERE


About Author:
Dipak Kumar Dash
M Pharm pharmaceutics
Production officer -Akorn india pvt ltd
dipak.dipak.dash@gmail.com

INTRODUCTION
Introduction In recent years, polymeric controlled drug delivery systems have evolved as one of the most attractive areas in drug delivery research. The drug release is controlled by properties of the polymer-drug system and also by other factors like pH, enzymes etc. Despite several advantages offered by the controlled drug release, one important problem pertinent to the entire field is that all the systems so far developed give release rates that are constant or decrease with time.Increased delivery on demand will be very beneficial in situations like, delivery of insulin for patients with diabetes mellitus, antiarrythmics in case of heart disorders and nitrates in case of angina pectoris. This increased delivery on demand can be achieved by using external feed back control systems such as magnetic control. The concept of magnetically controlled drug delivery for the first time was proposed be Tyle in 1988. A system has been developed to magnetize the carriers so that these particles can be retained on the target site by the application of an external magnetic field of appropriate strength. Magnetic fields are believed to be harmless to biological systems and adaptable to any part of the body.

Reference Id: PHARMATUTOR-ART-1619

Definition:
Definition Magnetic microspheres are supramolecular particles that are small enough to circulate through capillaries without producing embolic occlusion (<4 μm) but are sufficiently susceptible (ferromagnetic) to be captured in micro vessels and dragged in to the adjacent tissues by magnetic fields of 0.5-0.8 tesla (T).

CONCEPT
*  The use of magnetic force for site-specific drug delivery by using albumin microspheres containing magnetite appears to be a promising strategy.
*  Significant improvements in response can be incorporated and obtained with magnetic albumin microspheres delivery system compared with conventional and nonmagnetic microspheres drug regimens.

HISTORY OF MAGNETIC GUIDANCE
*  Tyle 1988
* Earliest use of magnet for selective delivery of clinical agents involved treatment of arterial thrombosis by use of carbonyl iron.

Merits :
Merits Therapeutic responses in target organs at only one tenth of the free drug dose .  controlled drug release within target tissues for interval of 30 min to 30h,as desired . Avoidance of  acute drug toxicity. Adaptable to  any part of the body. Demerits Expensive  Needs specialized magnet for targeting, advanced techniques for monitoring, and trained personnel to perform procedures. A large fraction (40%-60%) of the magnetite which is entrapped In carriers  ,is deposited permanently in target tissues.

Concept of magnetic targeting microspheres :
Concept of magnetic targeting microspheres Ideally magnetic microsphere are injected into an artery that supply given a site. As microsphere would be selectively and magnetically localized at the capillary levels, they would have free flow access through large particles arteries. Thus microsphere would serve as time released capsules system sitting in the desired location. The selective capillary localization of the microsphere can be achieved by applying greater field strength.

Characteristic of magnetic microsphere :
Characteristic of magnetic microsphere Particle size of drug carrier, can effect the degree of drug entrapment. In targeting, using the magnetic content of carrier & the magnitude of applied magnetic field are important. If a high magnetic content is incorporated thus amount of magnetic fields needed is reduced but the space available for drug entrapment decreases. Drug incorporation and magnetite has to be delicately balanced. Optimum magnetic content would be between 22-50% of drug weight in the drug carrier complex.

Magnetite :
Magnetite A ferromagnetic materials when incorporated in to microspheres makes them magnetically responsive so that they can be concentrated to the desired site by applying some magnetic field. Iron is a strong ferromagnetic material but due to its local tissue irritation it can’t be included in to microspheres. But such a problem is not seen when magnetite ferric oxide (Fe3o4) which is biologically compatible and also its ultra fine particle size makes it suitable material.

Method of preparation :
Method of preparation Two methods Phase separation emulsion polymerization (PSEP) Continuous solvent evaporation (CSE) Phase separation emulsion polymerization aqueous solution vegetable oil (Albumin+ drug+ magnetite) Emulsification Heat Cross linking agent Micro sp. Suspension separated from oil Dry & store at 4? C .

Continuous solvent evaporation :
Continuous solvent evaporation solution in volatile organic solvent (polymer + drug+ magnet) Auxiliary solution stiring Magnetic microsphere separated by centrifugation Freeze drying & storage at 4 ?C.

ANALYSIS OF  MOVEMENT


Evaluation of Drug release rate in vitro:
Evaluation of Drug release rate in vitro: 1. Dialysis method 2. Continuous column electron method Dialysis method Albumin   microsphere were taken in funnel, 3ml of phosphate buffer of 7.3 pH was added.  mouth of funnel is covered with cellophane & fastened with rubber band . Then funnel is inverted into a beaker containing 50 ml phosphate buffer. 2.5 ml of aliquots are withdrawn every half an hour and replaced with fresh buffer and estimated for drug release. Continuous column electron method Microspheres were immobilized on a column containing a fixed weight of glass wool ( 3.5 gm ) as support material & kept at 37OC.

They were subject in a constant flow of 50 ml phosphate buffer ( PH7.3 ) fraction were collected at intervals at half an hour. The amount of drug eluted was estimated. Characterization Carrier localization - gamma densitometry; gamma camera imaging; high frequency ultrasound. In vivo drug distribution - Standard proton magnetic resonance imaging. Microspheres localization- Ultrasound techniques. Particle size and shape- SEM .

ADVANTAGES
*    It allows high local concentration of therapeutic agents.
*    Controlled drug release within target tissue for intervals of 30 min to 30 hour, as desired
*    Avoidance of drug toxicity
*    Adaptable to any part of the body

DISADVANTAGES
*    Magnetic targeting is an expensive aspect.
*    Technical approach , manufacturing and quality control should be highly specialized.
*    Its needs specialized magnet for targeting  & advance technique for monitoring.
*    Trained personnel to perform procedures.

APLICATION
1. It is use for drug targeting.
2. Magnetic fluid hyperthermia.
3. High throughput DNA isolation.
4. Improvement in drug release.

REFERENCES
1. Y.W. Chien, Concepts and system design for the rate-controlled drug delivery, Drug and pharmaceutical sciences, Marcel Dekker Inc. York, 2nd Edn. 50 (1992): pp. 1-139.
2. S.P. Vyas  & R.K. Khar, Targeted and Controlled Drug Delivery.1st edn, CBS publisher & distributor New Delhi.
3. H.A. Lieberman, M.R. Martin & G.S. Banker, Pharmaceutical dosage forms: Disperse Systems vol-2.
4. American journal of pharmaceutical sciences.
5. dogpile.com
6. pubmed.com

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