Introduction
Nanomedicine describes medicine and pharmaceutical therapies applied on a nanometer scale, i.e.: one billionth of a meter. This is an area of pharmaceutical technology that is so new it barely exists. Once a mythical idea that led to several science fiction books and films, this concept is now entering the world of science fact. Although this technology often conjures images of tiny robots travelling around inside the body repairing damaged tissue, we are not at that stage just yet. The current reality is much more subtle but the future looks set for some exciting developments that could potentially be very significant to the field of medicine.

Current Technology
Currently the area of nanomedicine showing the greatest potential is the use of tiny polymeric drug carriers. Such materials can now be made in the form of spheres with diameters ranging from about 50 billionths of a meter. This can facilitate the transport of drugs to some of the smallest capillaries in the body. These nanospheres are designed to travel to specific sites within the body, release their payload of drug molecules and then degrade. Their degradation by-products are non-toxic and will ultimately be excreted from the body. Developments in polymer science have had a great influence on drug delivery. It is now possible to synthesise a wide variety of biocompatible biodegradable polymers that will release entrained drugs at a rate determined by the chemistry and physical form of the polymer. Drug delivery research is now at a very important stage in its development.

In recent years there has been revolutionary progress made in the field of healthcare. The knowledge now exists to cure many afflictions that were once thought incurable through the use of novel therapeutics. Many of these therapeutic methods cannot currently be used or are not being used to their full potential because they cannot be delivered into the body with the required control. An example of this is chemotherapy for the treatment of cancer. This involves saturating the body with toxic drugs, which can often result in harmful side effects such as reduced immune response to infection. By directing the drug molecules specifically to the site of a tumour a reduced quantity of drug would be required thus reducing the toxic effect on the body.

Advances in biotechnology now make it possible to control disease at the genetic level. These developments have lead to the creation of several new fields in the area of biopharmaceutical science. These new therapies are based on the interaction of nucleic acid drugs (DNA, Antisense, Antigene and Gene Therapy) with the genetic material of specific cells within the body. The Achilles' heel of these new biopharmaceuticals is that it is difficult to direct them to the specific site required for action. There is also another disadvantage to these therapies in that they are easily broken down by conditions within the body. Incorporation of such drugs into delivery devices may be the way forward.

Research at the University of Limerick
So how are such nanoparticulate devices produced? The answer is a complicated one that involves the use of molecules that self-assemble themselves during a chemical process. Here at the University of Limerick we use this procedure, which is known as 'emulsion polymerisation'. This involves the use of self-assembled spheres as a molecular 'mould' into which reactive monomer diffuses and polymerises to form solid spheres.

Figure 1: Schematic representation of a surfactant molecule

Molecules known as surfactants perform this bizarre self-assembly by virtue of their unusual structure. The process has been likened to putting transistors, resistors and diodes into a bag, shaking it around and pulling out a fully functional radio. The mechanism that causes surfactant molecules to self-assemble is a result of their amphiphillic nature. This means that the molecules are composed of two or more parts with each part being soluble in a different medium. Generally, a surfactant may have a hydrophilic head and a hydrophobic tail as shown in Figure 1.

Figure 2: The self assembly mechanism of micelle formation with increasing concentration of surfactant

Once the concentration of these molecules in an aqueous solution reaches a critical value they will arrange themselves so as to minimise the interaction of the hydrophobic tail with the water. In order to accomplish this the hydrophobic tails align themselves along side each other that, in some cases lead to the formation of a spherical structure called a micelle as illustrated in Figure 2. The size of these micelles is dependent on the length of the surfactant molecule and range from 10 - 100 billionths of a meter in diameter. Once there are millions of micelles spinning around in the aqueous medium a reactive monomer is introduced which is also hydrophobic. As can be seen from Figure 3, monomer molecules want to minimise their interaction with the water and for this reason they travel to the interior of the micelles where the are stable. The micelles will then swell to accommodate the monomer. The final part of the preparation of the nanoparticles involves the addition of initiator molecules that trigger a chain reaction within the micelles core leading to a polymerisation. Once the core of the micelles have been converted into a solid polymer sphere of approximately 200 - 1000 billionths of a meter in diameter the spheres may be removed from the emulsion and are ready for use.

Figure 3: Once monomer molecules diffuses into the micelle they are polymerised to form a solid nanosphere

Once produced these tiny particles appear as a fine powder that can have drug molecules either attached to their surface or absorbed into their core. At this stage the nanoparticles are solid spheres composed of polymer chains of a fixed length. This chain length is described by the polymer's molecular weight. For a specific polymer, an example being poly(n-butyl cyanoacrylate), the lower the molecular weight the faster it will degrade within the body and thus the faster the entrained drug is released. The specific site within the body to which the nanoparticles will travel is controlled by the surface chemistry of the nanoparticle. Molecules can be tethered to the particles' surface, which will cause selective uptake, by various organs within the body.

Future Research
Advances in analytical techniques have improved our ability to produce and image nanostructures. As seen in Figure 4 Scanning Electron Microscopy (SEM) uses an electron beam to image nanoparticles. They cannot be seen using standard optical microscopy because their diameter is smaller than the wavelength of visible light. SEM however has its disadvantages in that the powerful electron beam used can often vaporise the particles. A new technique is now becoming available that generates an image by passing a stylus back and forth over the surface of the particles. This stylus is much like the one used on a record player but is a few thousand times smaller. The technique is called Atomic Force Microscopy (AFM) (Figure 5) and its magnifying capability is such that it has been compared with the ability to count the grains of sand on a beach on earth, from the moon! At the moment there is a great deal of research being carried out in the area of nanotechnology. Materials that change their physical characteristics following exposure to stimuli such as light, heat and changes in pH are being developed. It has been proposed that such materials will lead to the first nano-scale robot arms and similar devices. By combining technologies it may be possible to create 'smart' nanoparticles that will be the next step towards true cellular level medicine.

Figure 4: Scanning Electron Microscope image of nanoparticles

In the 1960's the Nobel laureate Richard Feynmann predicted the use of 'small machines' to repair damaged cells within the body. Those machines may be almost here and they are small…very small.

Figure 5: Atomic Force Microscope image of the surface of agglomerated nanoparticles

Email: Niall.Behan@ul.ie

---