DRUG DELIVERY is a special form of drug delivery system where the pharmacologically active agent or medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells. The drug may be delivered 

To the capillary bed of the active sites, To the specific type of cell (or) even an

intracellular region. Ex- tumour cells but not to normal cells,

To a specific organ (or) tissues by complexing with the carrier that recognizes the target

DRUG DELIVERY

Poly(methyl methacrylate)-PMMA

In case of non-biodegradable drug carriers, when administered parenterally, the carrier remaining in the body after the drug is completely released poses possibility of carrier toxicity over a long period of time.

BIODEGRADABLA POLYMERS: Bio degradable carriers which degrade in

the body to non-toxic degradation products do

not pose the problem of carrier toxicity and are more suited for parenteral applications

NON-BIODEGRADABLE POLYMERS

Poly alkyl cyano acrylates is a potential drug carrier for parenteral as well as other

ophthalmic, oral preparations. Poly lactic acid is a suitable carrier for sustained release of narcotic antagonist, anti cancer agents such as cisplatin, cyclo phosphamide, and doxorubicin

Synthetic polymers

Sustained release preparations for anti malarial drug as well as for many other drugs have been formulated by using of co-polymer of poly lactic acid and poly glycolic acid.

Poly anhydride microspheres (40µm) have been investigated to extend the pre

corneal residence time for ocular delivery. Poly adipic anhydride is used to encapsulate timolol maleate for ocular delivery. Poly

acrolein microspheres are functional type of

microspheres

ALBUMIN: Albumin is a widely distributed natural

protein. It is considered as a potential carrier of drug or protiens (for either their site specific localization or their local application into anatomical discrete sites). It is being widely used for the targeted drug for the targeted drug delivery to the tumour cells

Natural polymers

Gelatin microspheres can be used as efficient carrier system capable of delivering the

drug or biological response modifiers such as interferon to phagocytes

STARCH: Starch belongs to carbohydrate class. It

consists of principle glucopyranose unit, which on

hydrolysis yields D-glucose. It being a poly saccharide consists of a large number of free OH groups. By means of these free OH groups a large number of active ingredients can be incorporated within as well as active on surface of microspheres

GELATIN:

Chitosan is a deacylated product of chitin. The effect of chitosan has been considered because of its charge. It is insoluble at neutral and alkaline Ph values, but forms salts with inorganic and organic salts. Upon dissolution, the amino groups of chitosan get protonated, and the resultant polymer becomes positively charged

CHITOSAN:

1. Bioadhesive microspheres: Adhesion can be defined as sticking of drug

to the membrane by using the sticking property of the water soluble polymers. Adhesion of drug delivery device to the mucosal membrane such as buccal, ocular, rectal, nasal etc can be termed as bioadhesion. These kinds of microspheres exhibit a prolonged residence time at the site of application and causes intimate contact with the

absorption site and produces better therapeutic action.

TYPES OF MICROSPHERES

This kind of delivery system is very much important which localizes the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microspheres are chitosan, dextran etc. The different types are therapeutic magnetic microspheres and diagnostic microspheres

2. Magnetic microspheres

It is used to deliver chemotherapeutic agent to liver tumor. Drugs like proteins and peptides can also be targeted through this system.

B. Diagnostic microspheres It can be used for imaging liver metastases and also can be used to distinguish bowel loops from other abdominal structures by forming nano size particles supramagnetic iron oxides.

A. Therapeutic magnetic microspheres

In floating types the bulk density is less than the gastric fluid and so remains buoyant in stomach without affecting gastric emptying rate. The drug is released slowly at the desired rate, if the system is floating on gastric content and increases gastric residence and increases fluctuation in plasma concentration. Moreover it also reduces chances of striking and dose dumping. One another way it produces prolonged therapeutic effect and therefore reduces dosing frequencies

3. Floating microspheres

Radio immobilization therapy microspheres sized 10-30 nm is of larger than capillaries and gets tapped in first capillary bed when they come across. They are injected to the arteries that lead to tumor of interest. So all these conditions radioactive microspheres deliver high radiation dose to the targeted areas without damaging the normal surrounding tissues. It differs from drug delivery sys- tem, as radio activity is not released from microspheres but acts

4. Radioactive microspheres

from within a radioisotope typical distance and the different kinds of radioactive microspheres are a emitters, ß emitters, α-emitters.

5. Polymeric microspheres The different types of polymeric

microspheres can be classified as follows and they are biodegradable polymeric microspheres and synthetic polymeric microspheres.

Natural polymers such as starch are used with the concept that they are biodegradable, biocompatible, and also bioadhesive in nature. Biodegradable polymers prolongs the residence time when contact with mucous membrane due to it’s high degree of swelling property with aqueous medium, results gel formation. The rate and extent of drug release is controlled by concentration of polymer and the release pattern in a sustained manner. The main drawback is in clinical use drug loading efficiency of biodegradable microspheres is complex and is difficult to control the drug release

A. Biodegradable polymeric microspheres

The interest of synthetic polymeric microspheres are widely used in clinical application, moreover that also used as bulking agent, fillers, embolic particles, drug delivery vehicles etc and proved to be safe and biocompatible. But the main disadvantage of these kinds of microspheres, are tend to migrate away from injection site and lead to potential risk, embolism and further organ damage

B. Synthetic polymeric microspheres

REASON FOR DRUG TARGETING: In the treatment or prevention or diseases. To reduce Pharmaceutical drug instability in

conventional dosage form solubility ,biopharmaceutical low absorption, high-membrane bounding, biological instability, pharmacokinetic / pharmacodynamic short half life, large volume of distribution, low specificity, clinical, low therapeutic index.

TARGETTING OF MICROSPHERES

Targeting of drugs to special cells and tissues of the body without their becoming a part of systemic circulation is a very novel idea. If a drug can be administered in a form such that it reaches the receptor sites in sufficient concentration without disturbing in extraneous tissue cells.Such products are prepared by considering-1.specific properties of target cells.2.nature of markers or transport carriers or vehicles, which convey drug to specific receptors.3.ligands and physically modulated components.

CONCEPT AND COMPONENTS OF TARGETTED DRUG DELIVERY SYSTEM

These are the microspheres containing substance inside which can be easily targeted by applying external magnetic field.Magnetic microspheres were developed:a)To minimize renal clearanceb) To increase target site specificityc) To entrap a wide variety of drugs d) In the entrapment of localised tumors in the religions of well defined blood supplye) For controlled release of peptide protein drugs such as LHRH, which have the short half life and otherwise need to be injected once or more daily as conventional parenteral formulation.f)To minimize reticulo endothelial clearance target site specificity

MAGNETIC MICROSPHERES

Particle size of a drug carrier can affect the degree of drug entrapment.Increase in size of the albumin microspheres due to the hydration can alter its body distribution.Use of sub-micron size microspheres minimises the incidence of pulmonary embolism that often encounters with particles greater than 7µm or particles which aggregate upon their vivo administration.The retention of magnetic microspheres at the target site is dependent on the “magnetic content” of the carrier & the magnitude of the “applied magnetic field”.

IMPORTANT CHARACTERISTICS OF MICROSPHERES & MAGNETIC MICROSPHERES

Although high magnetic content allows the use of smaller magnetic fields, it reduces the effective space available within the carrier for the drug entrapment.In targeting using Magnetic Microspheres, the magnetic field content of the carrier & the magnitude of applied magnetic field are important.

Certain cytotoxic drugs are active intracellular, but are normally discarded due to their poor intracellular influx. 

The poor efficacy of many therapeutic substances for intracellular bacterial & parasitic therapy is known. The intracellular delivery of the drugs by suitable means can obviate these problems.

For e.g. the biologically active streptomycin was released from albumin microspheres inside the phagocytic cells after ingestion and intracellular degradation of microspheres

INTRACELLULAR TARGETING:

DRUG RELEASE FROM MICROSPHERES

By placing the microspheres in screw capped glass container and stored them at following conditions:

Ambient humid condition � Room temperature (27+/-2 °C) � Oven temperature (40+/-2 °C) � Refrigerator (5 °C -8°C). �

Stability studies

New applications for microspheres are discovered every day, below are just a few: Assay - Coated microspheres provide measuring tool in biology and drug research.

Buoyancy - Hollow microspheres are used � to decrease material density in plastics (glass and polymer)

APPLICATIONS

Ceramics - Used to create porous ceramics used for filters (microspheres melt out during firing, Polyethylene Microspheres) � Cosmetics - Opaque microspheres used to hide wrinkles and give color, Clear microspheres provide "smooth ball bearing" texture during application (Polyethylene Microspheres)

Drug delivery - As controlled time release drug capsule made of, for example,

polymers. A similar use is as outer shells of microbubble contrast agents used in contrast-enhanced ultrasound.

� Electronic paper - Dual Functional microspheres used in Gyricon electronic

paper.

� Spacers - Used in LCD screens to provide a precision spacing between glass panels (glass) � Standards - monodispere microspheres

are used to calibrate particle sieves, and particle counting apparatus. � Retro reflective - added on top of paint

used on roads and signs to increase night visibility of road stripes and signs (glass) � Thickening Agent - Added to paints and epoxies to modify viscosity and buoyancy

1. Microspheres in chemotherapy: The most promising application of

microspheres are possible to used as carriers for anti- tumor agents. Enhanced endocytic activity and leaky vasculature administrated microspheres. Stealth microspheres are prepared by coating with soluble polyoxy ethylene. The accumulation of non-stealth microspheres in Reticulo Endothelial System (RES) may also be exploited for cancer chemotherapy.

OTHER APPLICATIONS

Microspheres have been recently used as a delivery vehicle for the transfer of plasmid DNA which leads to improve the transfer of plasmid DNA and their stability in the bio- Environment.3. Fluorescent microspheresThese are made up of polystyrene or poly vinyl toluene, mono disperse system ranging in size from 20nm to 4µm.

2. Microspheres for DNA Delivery

Preparation of fluorescent microspheres comprising, swelling the polymeric microsphere so that fluorescent dyes may enter the microsphere pores.

4. Adjuvant effect for vaccines An adjuvant effect of the microspheres/

nano particles with either matrix entrapped or surface adsorbed vaccines have been demonstrated in several studies on substances or oral administration.

The most applications of drug loaded ophthalmic delivery systems are for glaucoma therapy, especially cholinergic agonists like pilocarpine. The short elimation half life of aqueous eye drops can be extended from a very short time (1-3 min) to prolonged time (15-20 min) using microspheres which have biodegradable properties e.g: Poly alkyl cyano acrylate .

5. Microspheres for Ocular delivery

The major purpose of lymph targeting is to provide an effective anticancer

chemotherapy to prevent the metastasis of tumor cells by accumulating the drug in the regional lymph node. Example:

• Poly alkyl cyano acrylate microspheres bearing anticancer drugs for tumor of peritoneal cavity. • Poly (lactide-co-glycolide ) microspheres

for the lymphatic of diagnostic agents.