Site Specific Targetting

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A wide range of cellular, macromolecular and particulate carriers of different sizes, which are made of diverse range of biodegradable/ biocompatible materials have been exploited as potential drug delivery systems with the aim of improving cancer chemo-therapy.

Site specific drug delivery using the novel targeting approaches improves the therapeutic regime and also reduces the toxic side effects. The sequential events of this site specific drug delivery include the following events:

1. Localization of drug and carrier within the desired target organ (Organ targeting)

2. Recognition and interaction of the carrier with specific target cell(s) with in a tissue (Cellular targeting).

3. Delivery of the therapeutic concentration of drug to only the target cell/s.

An advanced strategy is to deliver the drug to different intracellular compartments within target cells via specific transport pathways. (Intracellular targeting)

Fundamentally they are two types of drug conjugates:

1. Drug + Carrier (Drug Carrier Conjugate)

2. Drug + Carrier + PEG + Ligand (Ligand Drug Carrier Conjugate)/ Magic Bullet

Drug may be a chemo-therapeutic agent; carrier may be a liposome/ nanoparticle/ resealed erythrocyte; PEG is poly-ethylene-glycol a polymer to avoid RES uptake; Ligand may be an antibody/ glycolipid/ glycoprotein etc. These are sterile, lyophilized, and available in various size ranges; generally administered in solution or suspension by I.V route.

The micro- environment around the tumour tissue offers many advantages to these drug conjugates for effective targeting of which some of them are as follows:

1. Vasculature surrounding tumour tissue is generally fenestrated with openings ranging in diameters from 100-200 nm. Permitting rapid entry of these novel drug conjugates.

2. The temperature around the tumour tissues is relatively very high; this helps in easy diffusion through carrier.

3. The lymphatic system around the tumour tissue is immature; allowing the drug carrier conjugate to stay for a longer time, resulting in "Enhanced Permeation and Retention Effect" (EPR).


Its operation is by passive mode of transport as described earlier the drug is entrapped in a carrier and made in a solution/ suspension form and given in I.V route.


Avoidance of Multi- Drug Resistance:

Tumour cells are characterized by over expression of cell membrane glycol-protein (P-gp) a membrane spanning ATPase located on plasma membrane. It acts as an efflux pump and expels the drug molecules which are absorbed via passive diffusion. This can be avoided by masking the drug in a carrier and preventing the exposure of drug molecule to the efflux pumps. Improved pharmaco-kinetic profile also adds up.

Ex: Doxorubicin when bounded to P-gp it is pumped out of the cell. When this is doxorubicin is entrapped in a liposome it prevented the contact of P-gp avoiding the drug efflux.

Research study:

Cuvier et. al 1992 demonstrated an enhanced cellular accumulation of doxorubicin following the administration of poly-iso-hexyl-cyano-acrylate nanoparticle bound doxorubicin (as compared to free drug) in a multi drug resistant tumour cell line.

Targeting to RES:

The drug conjugates are easily identified by the phagocytic cells of reticulo-endothelial system. These are rapidly engulfed and are transported to various organs like bone marrow, spleen and liver. This transport helps in exposure of these drug conjugates to tumour tissues in liver, spleen and bone marrow.

Research Study:

Ewer et al. demonstrated a reduced risk of cardio toxicity with liposome entrapped doxorubicin when compared with free drug preserving the anti-tumour activity.


It is similar to drug carrier conjugate but the surface pegylated to increase the circulation time by avoiding RES uptake and a ligand is attached to it to specifically attach the selective marker or expressed complimentary protein on the tumour cell surface. Its operation reflects active mode of targeting. The term "MAGIC BULLET" usually applied to this site specific targeting since the drug conjugate directly hits on the target site.


1. Site specificity.

2. Improved pharmaco-kinetics.

3. Avoidance of Multi- Drug Resistance.

4. Avoiding RES uptake

Research Study

Omic C.Farokhzad et. al studied the nanoparticle- aptamer bioconjugates for targeting prostate cancer. Demonstrating that these bioconjugates showed increased uptake in the tumour cells exposing prostate specific antigens (markers) to that of those which do not express this protein.


1. Ewer MS, Martin FJ, Henderson C, et al. 2004. Cardiac safety of liposomal anthracyclines. Semin Oncol, 31:161-81.

2. Cuvier C., Roblot- Trepuel L, Millot.J, Lizard G, Chevillard s. Manfiat M. Courver P. and Poupon M.F. (1992) Biohem, Pharmacol. 44, 509.

3. Omid C. Farokhzad, Sangyong Jon, Ali Khademhosseini, et. al. 2004. Nanoparticle-Aptamer Bioconjugates: A New Approach for Targeting Prostate Cancer Cells.pdf.

4. Targeted & Controlled Drug Delivery (Site specific drug delivery); pgs: 515-520, S. P. Vyas & R. K. Khar. C. B. S. Publishers. [access date: 25th June, 2010]

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About the Author

Santosh kumar. JH's picture

Key Skills:-

Lean Methodology

Six Sigma Expertise

Formulation Operations


Jyothi's picture

hello sir, nice meeting you your blog is very nice , and it will be useful to budding pharmacists in a good manner


Santosh kumar. JH's picture

This is an attempt to make the concepts in a simple and lucid manner with the help of visuals, so that young buddies can easily get them at the first sight.
Arun Abraham's picture

Dear Santosh, Good work! really pleased to meet you and notice that you are good at understanding the concepts and putting that across.

Arun Abraham M.Pharm,MBA,(PhD) Chief Learning Officer Leads Health Bangalore.

Santosh kumar. JH's picture

Thank you sir... Great to see you in this website.
Payal Dande's picture

Your pictures made it easier to differentiate the various types of site specific drug conjugates.
Santosh kumar. JH's picture

Dear Ma'am I tried to make the best pictures to make it more clear. Thank You!
Prof. J. Vijaya Ratna's picture

Santosh Well done. Good explanation and good images. Vijaya Ratna
Santosh kumar. JH's picture

This is the result of your support and inspiriation. Thank you ma'am.
kranthi kumar's picture

Dear Santosh, I am proud to work along with you. This blog is explained clearly and the pictures are attractive and supportive.
Santosh kumar. JH's picture

I think, if we picturize our understandings it will definately be catchy and it could be easily followed by many. I do fell great pleasure in working with you. Thank You!

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