4.2. Classes of Drug Delivery Devices

The types of drug delivery device that have been and are being developed can be classified into four groups, depending on the method used to modify the drug properties.

4.2.1. Polymeric Systems

A great deal of research has been conducted into the use of polymers to develop means of controlling delivery of drugs to the human body. Within this class there are four sub-divisions, classified by the mechanism which controls the rate of drug release.

4.2.1.1. Diffusion Control
In many cases rate of release of a drug from a device is controlled by the rate at which the drug diffuses through a polymer. This class is further subdivided according to how the drug is held in the polymer. If drug is retained in a reservoir it is known as a reservoir device. However, when drug is dispersed throughout the polymer, it is known as a matrix device.
 
4.2.1.2. Chemical control
Polymeric drug delivery devices have been developed in which the polymer is susceptible to breakdown by agents present in the body (usually water, or enzymes). Two scenarios exist, one in which drug is held inside a biodegradable polymer, and ones in which the drug is chemically linked to a polymer by a bond that is biodegradable. The later are known as pendant chain systems, and the polymer is often soluble.
 
4.2.1.3. Solvent control
Another mechanism for controlling the release of drug from a device involves the use of a solvent, which in the case of the human body is water. In one class the solvent diffuses into the device and causes swelling, i.e. swelling controlled. In another case the device contains a high concentration of salt to which the solvent is attracted by osmosis through a semi permeable membrane, and the resulting influx of water is harnessed to expel a solution of the drug out of an orifice in the device.
 
4.2.1.4. Externally activated or modulated
The last class of polymeric device is being developed in order to give some form of control to the release that can be triggered by external means. Two examples include the use of magnetic beads, implanted in a polymer along with the drug, and activated by subjecting the beads to an external, oscillating magnetic field, and the use of externally applied ultrasound energy to increase drug release from polymer encapsulated drug.

4.2.2. Drug Modification/Protection

An alternative approach is modify the drug so that it is protected form the environment until it is needed, or the environment is protected from it, (as would be the case for drugs that are toxic to certain organs).

4.2.2.1. Produg formation
A prodrug is an in active from of a drug which is converted to the active form in the body. A classic example of a prodrug is the drug L-dopa, used in the management of Parkinson's disease.
 
4.2.2.2. Conjugation to a homing molecule
A great deal of interest has been generated by the prospect of developing a magic bullet that will home in on the disease area and deliver drug. This is particularly attractive in the case of cancer drugs, which are often highly toxic to many normal cells in the body, as well as the cancer cells. In this way the drug can be made to avoid areas in which it would cause damage, at the same time delivering a large payload to the target site.
 
4.2.2.3. Liposomal entrapment
It is possible to form micro-vesicles that contain a drug. These bilayered micro-vesicles, known as liposomes, are formed spontaneously when phospholipids contact an aqueous environment. Phospholipids are naturally occurring amphipathic molecules (contain both a hydrophilic and hydrophobic region). If they contact a solution of drug, they will form a vesicle entrapping some of the drug solution in the interior.

 

4.2.3. Pumps

One can imagine that if drug is in solution it would be very convenient to pump it into the body through a thin catheter. This is in fact the method of choice in hospitals, and currently there are sophisticated syringe pumps which are available to be programmed to pump a drug solution through an intravenous line. This, however, requires that the recipient be under constantly supervision by trained personnel, and also that the protective barrier of the skin is broken to allow insertion of a needle. This means that intravenous injection of a drug is an expensive proposition, which can lead to complications such as infections. One of the first attempts to regulate insulin in diabetes centered on the development of a implantable pump containing insulin solution which could be delivered in a metered doses into the blood stream. For the system to exactly mimic the delivery system of the body requires a sensor which can measure blood glucose level and feed this information back to the pump to administer insulin only when blood glucose levels are high. This is a closed-loop, feedback mechanism. Early versions were simpler, and merely pumped a continuous low, or basal dose of insulin, and the patient was required to administer external insulin by the usual injection routes after a meal.

4.2.4. Modification of the site of delivery

It is also possible to control how the body takes a drug up by changing either the properties or the location of the site of administration.

4.2.4.1. Use of enhancers
Many drugs can not pass through barriers such as the skin, or the nasal mucosa, so one approach to deliver them by these route is to change the skin permeable either by the use of chemicals known as enhancers, or by physical methods such as the use of electrical current (iontophoresis) or ultrasound (sonophoresis).
 
4.2.4.2. Shift in absorption zone
It is also possible to change the site of delivery by protecting the drug so that it will pass the first site, and arrive at a site where it is more likely to be absorbed. This is the case with drugs that are absorbed through the intestine, but not throughout the stomach, where they arrive from the mouth. If the drug is destroyed in the stomach, it must be protected, and polymeric coatings have been developed that remain in tact in acid conditions, but break down in the alkaline environment to the upper intestine. These coatings are known as enteric coatings.