Structural Biochemistry/Drug Targeting

Drug Targeting

In order to delivery drug to the desired destination, targeting is an important subject in drug delivery. Ligand is a substance that forms a complex with a biomolecule to serve for a biological purpose. There are three classes of ligands that are commonly used for drug delivery targeting. Antibodies and/or antibody fragments, peptides, and aptamers. Depending upon the situation of targeting, different type of ligand is used.

Reason of Drug Targeting and its Consequences

Drug targeting can be defined as the method and efficiency of delivering drugs to a target organ or system. Although this may seem like a simple process (just eat it or inject it into the blood right?), there are actually so many obstacles that have to be solved that it takes pharmaceutical companies years to develop one drug. These challenges include if the drug actually makes it to the target organ, and if it makes it to the organ in significant amounts that would actually be of benefit. Its common knowledge that if drug is eaten, it'll eventually end up in the blood and go everywhere in the body. What is not usually knows is if the drug is too thinly spread out over the body to be of any use, and the consequences of these drugs arriving at an non-target organ.

The fact that drug concentrations could be diluted to the point where it has no effect could be linked to a pharmaceutical's attempt in finding out the dosage of this drug. When testing a drug, scientists must find out how much of the drug could be administered to give a significant effect, while also testing for if increasing the dosage would increase the side effects. A balance of these two must be met in order for a drug dosage to be determined. Some variables would include the patient's body mass, age, blood levels, health of kidney and liver, and other medications the patient is taking. All these factors would play a role in determining how much drug to administer to the patient. If a patient has healthy liver, there's a good chance that a lot of the drug is going to be destroyed before it reaches the bloodstream. If the patient has low amount of blood, not a lot of drug has to be administered because it wont be as diluted. other medications the patient is taking could have chemical reactions that could lead to serious side effects. Another factor to take into account is the chemical weight and properties of the drug. If the drug has high molecular weight, not as much of the drug needs to be administered.

Mainly, pharmaceuticals are more concerned with what would happen if a drug meant for the kidney ends up near the lungs, or something similar to this. This could be called side effects. Often this is solved by observing the carbohydrate chains on the surface of cell membranes to discover what receptors cells of specific organs have. Developing a drug that fits into most of these receptors (a broad and commonly structured drug) would increase the chances of side effects. It is therefore crucial to develop a drug that binds to a cell's receptor as specifically as possible to reduce side effects. Discovering side effects and minimizing these side effects is a big part of getting a drug pass the examination tests and get on the shelves of pharmacies.(5)

Anti-microbial drugs targeted at different levels

At cell membrane level

Two drugs that target harmful microbes at the cell membrane level include polymyxins and nystatin. Polymyxins interfere with bacterial cell membrane, and therefore bacteria cannot function as osmotic barriers. The functional distinction between polymyxins and nystatin is that nystatin interferes with cell membranes of fungi and yeast whereas polymyxins disrupt bacterial cell membrane. Nystatin will bind to ergosterol, an essential component found in fungi cell membrane, which leads to cell membrane interruption that is representative with appearances of holes in the membrane.

Other groupings of anti-microbial drugs by their targets

At DNA level

Fluoroquinolones, or Cipro, inhibits synthesis of nucleic acids, such as DNA or RNA, by preventing gyrase, an enzyme needed for DNA replication, from unzipping. As a result, there is no DNA replication. Fluoroquinolones is broad-spectrum and extremely potent and thus can be used on difficult to treat bacteria, such as Bacillus anthracis, which causes anthrax, and Pseudomonas aeruginosa. Another anti-microbial drug that is targeted at the DNA level is rifampin, which is used to treat TB by inhibiting prokaryotic RNA polymerase, which in turn prevents transcription and therefore, no production of mRNA. The bacteria cannot live without these essential proteins.

At protein synthesis level

Linezolid, or Zyvox, disrupts the initiation of protein synthesis, and thus is used to treat methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), which are two of the most difficult pathogens to treat. Other antimicrobials acting at the protein synthesis level include streptomycin, gentamicin, tetracyclines, and erythromycin.

References

"Antibody Fragmentation." Antibody Fragmentation. N.p., n.d. Web. 28 Oct. 2012. <http://www.piercenet.com/browse.cfm?fldID=4E03B016-5056-8A76-4ECA-982DA6CAAC8A>.

"Creative Biolabs." Creative Biolabs. N.p., n.d. Web. 28 Oct. 2012. <http://www.creative-biolabs.com/phagedisplay1.htm>.

Tortora, Gerard J., Berdell R. Funke and Christine L. Case. Microbiology: An Introduction 10th ed. Boston: Benjamin Cummings :, 2010. Print. | Chapter 20| page 600}

5. Medicine by Design, US Department of Health and Human Services,NIH Publications, Reprinted July 2006