Fahad Drug Targeting

7/31/2019 Fahad Drug Targeting

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A PRESENTATIONON

DRUG TARGETING

PresenterFahad Hussain

Roll: ASH 1003MS 113MM. Pharm, Department of Pharmacy

Noakhali Science and Technology University

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DRUG TARGETING

BackgroundProblems 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.

isnt there any solution

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DRUG TARGETING

Targeted drug delivery is a method of delivering medication to a

patient in a manner that increases the concentration of themedication 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 sideeffects.

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ADVANTAGESOF 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.

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CLASSIFICATIONOF DRUG TARGETINGDrug targeting has been classified into three types:

First Order

It refers to restricted distribution of the drug-carrier system to the capillarybed of a predetermined target site, organ or tissue. Compartmentaltargeting 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 cellsand not to the normal cells is referred as second order drug targeting.The selective drug delivery to the Kupffer cells in the liver** exemplifiesthis approach.

Third OrderThe third order targeting is defined as drug delivery specifically to the

intracellular site of target cells. The receptor based ligand-mediatedentry of drug complex into a cell by endocytosis, lysosomal degradationof carrier followed by release of drug intra-cellularly or gene delivery tonucleolus 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

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Drug Targeting

Passive Targeting Active targeting

Direct local application

Tumor microenvironment

Leaky Vasculature

Antibody targeted

Carbohydrate targeted

Receptor targeted

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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 thetarget 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 theaffected zone

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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/ drugcarrier within the target

Number and affinity of targeting moieties

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PASSIVETARGETINGAPPROACHES

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

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ACTIVETARGETINGAPPROACHES

Carrier specificity can be enhanced, through surfacefunctionalization with site-directed ligands which bind or interactwith specific tissues

Biochemical targets Organs, Cellular, Organelles, Intracellular

Physical/External Stimuli Ultrasound, Magnetic field10


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MAIN APPROACHESTO 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 syntheticCarrier that is then targeted to the disease site.

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DRUG TARGETING: PRODRUGS

Compounds that undergo biotransformation prior toexhibiting pharmacological effect

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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 convertsinto active morphine in vivo.

Prednisone, a synthetic cortico-steroid drug, is bioactivated by the liverinto the active drug prednisolone.

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DRUG TARGETING: MAGNETIC DRUG TARGETING

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The Biophysical Targeting Technique

Using magnetic nanoparticles (ferrofluids) Enhancing efficacy

Minimum side effects Ferromagnetic element (e.g. an implant) is placed in amagnetic field, it becomes magnetically energized


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Solid tumor

Apply magneticfield to concentrateparticles

Modulate field torelease drug fromparticles

Inject NMPs IV,NMP will circulate

through the blood stream

Other options:1 - Direct injection intotumor site2 - Coating NMP with

antibodies to target

MAGNETIC DRUG TARGETING CONTINUING: GUIDED DRUG DELIVERY

Ability to addlocalized heatingcombined with drugdelivery


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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 ofanticancer agents, e.g. radionuclides, cancer specificantibodies, and genes

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DRUG TARGETING: LIPOSOMES

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These are vesicular concentric structures, range in size from a nanometer to several

micrometers, containing a phospholipids bilayer and are biocompatible, biodegradableand non immunogenic.

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


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TWO-STEPS

TARGETING

Specificallybinding to

tumor cellBind

chromosomalDNA in target

tumor cell
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DRUG TARGETING: TRANSDERMAL APPROACH

Transdermal drug delivery system is topically administered

medicaments in the form of patches that deliver drugs forsystemic effects at a predetermined and controlled rate.

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

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TRANSDERMAL APPROACH CONTINUING:

In theory, transdermal patches work very simply. A drug is applied in arelatively high dosage to the inside of a patch, which is worn on the

skin for an extended period of time. Through a diffusion process, thedrug enters the bloodstream directly through the skin.

Since there is high concentration on the patch and low concentration inthe blood, the drug will keep diffusing into the blood for a long periodof time, maintaining the constant concentration of drug in the bloodflow. 21


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DRUG TARGETING: BRAINTARGETEDDRUGDELIVERYSYSTEM

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 ofneurological disorders.

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

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

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BRAINTARGETEDDRUGDELIVERYSYSTEM CONTINUING:

Advances in understanding of the cell biology of the BBB haveopened new avenues and possibilities for improved drug delivery tothe CNS.

Various strategies that have been used for manipulating the blood-

brain barrier for drug delivery to the brain include osmotic andchemical opening of the blood-brain barrier as well as the use oftransport/carrier systems.

Other strategies for drug delivery to the brain involve bypassing theBBB. Various pharmacological agents have been used to open the

BBB and direct invasive methods can introduce therapeutic agentsinto the brain substance.

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CONCLUSION

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

Targeted delivery of drugs, as the name suggests, is to assist the drugmolecule to reach preferably to the desired site. The inherentadvantage of this technique has been the reduction in dose & sideeffect 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 hasbecome wiser. Manifestation of these strategies in clinical now seemspossible in near future.

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Fahad Drug Targeting