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Targeted Drug Delivery

Now, since many biologics are given as monoclonal antibody which actually target the cell or target the sick cell. So let me try to cover the targeted drug discovery in general. What is the purpose of targeted drug delivery? Well, we want to deliver and accumulate the drug at the site of action for maximum efficacy. Not only that we want to limit the distribution of the biologics to non-target site. and thereby reducing the side effect.
Mechanisms of targeting: three levels.
First order targeting: the drug is delivered to the capillary bed of the site of action.
Second order targeting: the drug is delivered to the special cell type. For example, delivered to the tumor cells.
And third order targeting: the biologics is delivered to intracellular space of the target cells Now, this is the most difficult to do, but is most effective.
Let’s look at one example this is the drug targeting with emulsion. Here is the drug emulsion. It’s injected via the splenic artery into the spleen where you have a cancer splenic tumor. Now by the time, the drug gets there, you can activate the electromagnetic device which is outside the system and trigger the release of the cytotoxic cocktail to the tumor, only in the vicinity of the tumor. So this is targeting delivery. Now, the modes of targeting. Let me talk about this a little bi,t modes of targeting.
Passive targeting: that is to say the drug is drawn to the target. It utilizes the natural disposition pattern of the carrier system. The typical example for this, for passive targeting is monochrome antibody and the liposome. On the other hand, it is the active targeting. That is to say that the drug seeks out the target actively.
That is to change the natural disposition of the carrier. That is to work on the carrier. For example, the immunoliposome antibody that is covalently bound to each other. So let’s look at one example of active targeting. In this case, it is an immunoLiposome. For example, on the target cell, on the surface of the target cell, there’s a special protein that is expressed on the surface of the target cell. So based on this target cell or the protein on the target cell, we then made an antibody that is specific to that surface protein. We then couple the drug with the antibody and encapsulated into a liposome.
So when the liposomal preparation is administered to the host system, the antibody will seek out the target cell, the protein on the target cell, coupled with the target cell and release the drug to the target cell. So this is active targeting. On the other hand, the normal cell since it does not express protein, a specific protein on the surface of the cell. And therefore, there’s no immunospecific binding and because of that the normal cells are not affected. So in the active targeting, the drugs or the biologics only affect the sick cell but not the normal cell.

Proteins and peptides with demonstrated activity on the molecular and/or cellular level often fail to produce sufficient efficacy when applied in vivo, largely because of their unsatisfactory pharmacokinetic profiles. These include poor oral bioavailability, inadequate stability and shelf life, immunogenicity, short plasma half-life, and poor penetration across biological membranes. The design of delivery systems for biologics remains challenging, especially to achieve site-specific pharmacological actions and to reduce the undesirable systemic adverse effects.

Targeted drug delivery is a strategy that selectively and preferentially delivers therapeutic agents to a target site. Three levels of targeting are elaborated, first level to target the capillary bed of the site of action, second level to target the special cell type, and the third level to target the intracellular cells. A cytotoxic cocktail targeted a splenic tumor was presented as an example of the second level targeting. Further, the mode of targeting maybe classified as being passive or active. Monoclonal antibody is considered a passive targeting while immunoliposome is an active targeting platform

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Pharmacotherapy: Understanding Biotechnology Products

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