1

A PRESENTATION ON

DRUG TARGETING

PresenterFahad Hussain

M. Pharm in Clinical Pharmacy & Pharmacology,

Department of PharmacyNoakhali Science and Technology

University.www.PharmaMirror.com

2

DRUG TARGETING

Background

Problems associated with Systemic Drug Administration

Even bio-distribution of pharmaceuticals throughout the

body

The lack of drug specific affinity toward a pathological site

The necessity of a large total dose of a drug

Non-specific toxicity and other adverse side-effects.

isn’t there any solution

3

DRUG TARGETING

Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others.

Objective• Provide therapeutic concentration of drugs at the site

of action• Reduce systemic toxicity• Increase patient compliance

This improves efficacy of the drug while reducing side effects.

4

ADVANTAGES OF DRUG TARGETING

Drug administration protocols may be simplified.

Drug quantity required to achieve a therapeutic effect

may be greatly reduced as well as the cost of therapy.

Drug concentration in the required sites can be

sharply increased without negative effects on non-

target compartments.

5

CLASSIFICATION OF DRUG TARGETINGDrug targeting has been classified into three types:

First Order

It refers to restricted distribution of the drug-carrier system to the capillary bed of a predetermined target site, organ or tissue. Compartmental targeting in lymphatics*, peritoneal cavity, cerebral ventricles, lungs, joints, eyes, etc.

Second Order

The selective delivery of drugs to a specific cell type such as tumor cells and not to the normal cells is referred as second order drug targeting. The selective drug delivery to the Kupffer cells in the liver** exemplifies this approach.

Third Order

The third order targeting is defined as drug delivery specifically to the intracellular site of target cells. The receptor based ligand-mediated entry of drug complex into a cell by endocytosis, lysosomal degradation of carrier followed by release of drug intra-cellularly or gene delivery to nucleolus is an example for this approach.

* A network of vessels that conveys electrolytes, water, proteins, etc in the form of lymph from the tissue fluids to the bloodstream.

** Phagocytic cells that line the sinusoids of the liver

6Direct local application

Tumor microenvironment

Leaky Vasculature

Antibody targeted

Carbohydrate targeted

Receptor targeted

7

DRUG TARGETING

Principal schemes of drug targeting currently investigated in various experimental and clinical settings include:

• Direct application of the drug into the affected zone (organ, tissue)

• Passive accumulation of the drug through leaky vasculature (tumors, infarcts, inflammation)

• ‘physical’ targeting based on abnormal pH and / or temperature in the target zone, such as tumor or inflammation (pH- and temperature-sensitive drug carriers)

• Magnetic targeting of drugs attached to paramagnetic carriers under the action of external magnetic field

• Use of vector molecules possessing high specific affinity toward the affected zone

8

DRUG TARGETING

The parameters determining the efficacy of drug targeting:

• Size of the target

• Blood flow through the target

• Number of binding sites for the targeted drug/ drug carrier within the target

• Number and affinity of targeting moieties

9

PASSIVE TARGETING APPROACHES

Take advantage of natural anatomical structures or physiological processes,

which direct carrier in vivo distribution

Pathophysiological factors – Inflammation, Infection, EPR effect

Physicochemical factors – Size, Molecular weight

Anatomical opportunities – Catheterization, Direct injection

Chemical approaches – Prodrugs, Chemical delivery systems

Fig: Spontaneous drug accumulation in `leaky' areas

10

ACTIVE TARGETING APPROACHES

Carrier specificity can be enhanced, through surface functionalization with site-directed ligands which bind or interact with specific tissues

Biochemical targets – Organs, Cellular, Organelles,

Intracellular

Physical/External Stimuli – Ultrasound, Magnetic field

11

MAIN APPROACHES TO TARGETING

Retrometabolic Systems: Individual drug molecules chemically modified to

target particularly to the disease site.

Carrier – Based Systems: Drug is first packaged non-covalently into a

synthetic Carrier that is then targeted to the disease site.

12

DRUG TARGETING: PRODRUGS

Compounds that undergo biotransformation prior to exhibiting pharmacological effect

13

PRODRUG CONTINUING: OVERCOMING BARRIERS

Chemically linking pro-moiety to form prodrug

Biotransformation

Release of parent drug

Barrier is circumvented

Examples: 6-Monoacetylmorphine (6-MAM) is a heroin metabolite which

converts into active morphine in vivo. Prednisone, a synthetic cortico-steroid drug, is bioactivated by

the liver into the active drug prednisolone.

14

DRUG TARGETING: MAGNETIC DRUG TARGETING

The Biophysical Targeting Technique

• Using magnetic nanoparticles (ferrofluids)• Enhancing efficacy• Minimum side effects

• Ferromagnetic element (e.g. an implant) is placed in a magnetic field, it becomes magnetically energized

Solid tumor

Apply magnetic field to concentrate particles

Modulate field to release drug from particles

Inject NMPs IV,NMP will circulate through the blood stream

Other options:1 - Direct injection into tumor site2 - Coating NMP with antibodies to target

MAGNETIC DRUG TARGETING CONTINUING: GUIDED DRUG DELIVERY

Ability to add localized heating combined with drug delivery

17

MAGNETIC DRUG TARGETING CONTINUING: ADVANTAGES

Magnetic drug targeting is used to treat malignant tumors loco-regionally without systemic toxicity.

Magnetic particles used as “carrier system” for a variety of anticancer agents, e.g. radionuclides, cancer – specific antibodies, and genes

18

DRUG TARGETING: LIPOSOMESThese are vesicular concentric structures, range in size from a nanometer to several micrometers, containing a phospholipids bilayer and are biocompatible, biodegradable and non immunogenic.

Liposomes have generated a great interest because of their versatility and have played a significant role in formulation of potent drugs to improve therapeutics. Enhanced safety and efficacy have been achieved for a wide range of drug classes, including antitumor agents, antiviral, antimicrobials, vaccines, gene therapeutics etc.

TWO-STEPS TARGETING

Specifically binding to tumor cell

Bind chromosomal DNA in

target tumor cell

20

DRUG TARGETING: TRANSDERMAL APPROACH

Transdermal drug delivery system is topically administered medicaments in the form of patches that deliver drugs for systemic effects at a predetermined and controlled rate.

A transdermal drug delivery device, which may be of an active or a passive design, is a device which provides an alternative route for administering medication. These devices allow for pharmaceuticals to be delivered across the skin barrier.

21

TRANSDERMAL APPROACH CONTINUING:

In theory, transdermal patches work very simply. A drug is applied in a relatively high dosage to the inside of a patch, which is worn on the skin for an extended period of time. Through a diffusion process, the drug enters the bloodstream directly through the skin.

Since there is high concentration on the patch and low concentration in the blood, the drug will keep diffusing into the blood for a long period of time, maintaining the constant concentration of drug in the blood flow.

22

DRUG TARGETING: BRAIN TARGETED DRUG DELIVERY SYSTEM

The brain is a delicate organ, and evolution built very efficient ways to protect it. The delivery of drugs to central nervous system (CNS) is a challenge in the treatment of neurological disorders.

Drugs may be administered directly into the CNS or administered systematically (e.g., by intravenous injection) for targeted action in the CNS. The major challenge to CNS drug delivery is the blood-brain barrier (BBB), which limits the access of drugs to the brain substance.

Fig: Central Nervous System-selective Estrogens: A Safe Estrogen Therapy

23

BRAIN TARGETED DRUG DELIVERY SYSTEM CONTINUING:

Advances in understanding of the cell biology of the BBB have opened new avenues and possibilities for improved drug delivery to the CNS.

Various strategies that have been used for manipulating the blood-brain barrier for drug delivery to the brain include osmotic and chemical opening of the blood-brain barrier as well as the use of transport/carrier systems.

Other strategies for drug delivery to the brain involve bypassing the BBB. Various pharmacological agents have been used to open the BBB and direct invasive methods can introduce therapeutic agents into the brain substance.

24

CONCLUSION

Research related to the development of targeted drug delivery system is now a day is highly preferred and facilitating field of pharmaceutical world. It has crossed the infancy period and now touching height of growths from the pharmacy point of view.

Targeted delivery of drugs, as the name suggests, is to assist the drug molecule to reach preferably to the desired site. The inherent advantage of this technique has been the reduction in dose & side effect of the drug.

Overall it may be concluded with the vast database of different studies, the science of site specific or targeted delivery of these drugs has become wiser. Manifestation of these strategies in clinical now seems possible in near future.