The History of Drug Delivery Systems
Traditionally the drug delivery systems that existed consisted of simple chemical compounds that were dispensed orally either as a liquid, or as pills and in some cases given as injections. Recently with the development and more knowledge of how the body works and the understanding of chemical compounds, drug formulations that control the rate and period (time released drug) of its delivery and application to targeted areas of the body have become popular.
The improvements in the delivery of drugs followed the research findings that resulted in the advances in the understanding of the human body and how it works. The physician of the earliest civilizations dispensed drugs in the form of pills ointments, and liquids. The literature in early African cultures speaks to the witch doctors whose responsibility was to dispense drugs made from the local herbs. It was not until 1665 after the circulatory system was understood that intravenous injections were used in the medical practice.
Before 1850 evidence has been found where materials such as wood and ivory were used with metals such as iron, gold, silver and copper to make various prosthetic devices such as teeth and noses and to fix fractured bones. The problems faced in those early years were that the patient could not endure the long surgeries to enable the doctors to perform the procedure because there was no anesthesia. Between 1850 and 1925 the discovery of anesthesia and X -- Rays coupled with the introduction of aseptic surgical procedures enabled the doctors to performance procedures without the risk of post surgical infections.
From 1925 to the present advances were made in the use of different biomaterials. The development of cobalt chrome and stainless steel alloys in the industrial sector contributed to the use of these materials in surgery. The advancements in chemistry in the 1940's and the1950's, produced polymers and plastics that found their way in the medical field. Coupled with the production of penicillin and other antibodies that reduced the risk of infection these materials have been improved and are now used extensively in the medical field.
Present Developments
The present drug delivery systems (time released medication for example) have specific problems that bioengineers are attempting to provide answers for. These questions include the fact that the effectiveness of many drugs are reduced because of the degradation that occurs before the administered drug reaches the targeted areas. Once taken and digested, time released medication administer the treatment continuously, and not providing relief only when necessary and in some cases can cause adverse effects to non-infected areas. Medications given in the form of injections could be made more cheaply, and could be administered with less pain and suffering to the patient if they were given orally.
The investigations into new materials for drug delivery systems that will delivery medication intact to the targeted area have been ongoing. The research and use of polymeric, microsphers, polymers micelles, and hydrogel type materials have proven to be very effective. These materials have perfected drug targeting specificity, lowering the of drug toxicity, improving the absorption rates, and providing protection of pharmaceuticals against biochemical degradation.
It has been found that cells will do their structural work with two primary man made materials. These are non metallic minerals and polymers. Polymers can be classified as elastomers and plastics. Elastomers is more rubbery and have fewer cross links while plastics are more crystalline.
Silicone rubber is made from sand and was first used for shunts in 1955. It is biological compatible. Its compatibility has been justified from a variety of clinical trials using a number of different grades and used in a variety of applications. It is has shown to have superior biocompatibility and mechanical properties. It can be sterilized by steam, radiation or ethylene oxide. Silicone rubber is commonly used for catheters, the gel for breast transplants. It is also used as a functional membrane in kidney dialysis and blood oxygenation machines. In orthopedics it is used to support arthritic fingers and wrists.
Dacron is another material used . It is used for blood vessel prostheses. The pores in the fabric can be filled with coagulated blood, which is the replaced by tissue called neointima. This serves as a biological wall between the dacron and the blood. Dacron is also used in the prosthetic heart valve.
The product polytelraflaoroethylene is used to produce small blood vessels, prostheses and is also used to make heart valves, ligaments and artificial ossicles for the ear.
Various types of polymers and elastomers have been developed and used as biodegradable implants, but there is still the problem that living organisms have one motivation, that is to seek out foreign agents that enter the body and either destroy them or encapsulate them. Biomaterials should therefore be able to avoid the body's natural behavior to either encapsulate or destroy. It is therefore necessary to find materials for implantation that will become invisible to the cells chemical reaction or that has the same chemical composition as the cells. These materials should have molecules which look life biological materials, so that they will not be attacked by cells.
Polymers that are used to encapsulate drugs for delivery and implantation must have the same basic qualities of any biomaterials that are used for implantation of other devices. It should be geometrically compatible with the body, it must not poison the body' it must not corrode in the presence of body fluids' it must be free of toxic substances, and it should be easily sterilized. In must cases the drug delivery system should not need replacement, but should disintegrate in the body.
Two types of polymer system are in use. They are both microspheres, because of their size and shape. The reservoir device enables the pharmaceutical product (the drug) to be enclosed or wrapped in the interior of the polymer shell, while the matrix device has the drug trapped within a polymer network. The release of the drug from both these two systems follow the fundamental molecular transport processes that of diffusion and convection. The newer replication of these systems is being investigated. These will be designed using biodegradable polymer systems that will break down into lactic and glycolic acids, and is then reduced to carbon dioxide and water, the medication is then released and the waste expelled from the body.
Future Development
There is always the quest to not only to find new drugs but also to find or develop new ways of administering the medication. The goal of all drug delivery system is to place medication intact and to the specific part of the body through a device that can control the amount administered either by a physiological or by a chemical trigger. To make this realistic bio- engineers are working with micro- and nanotechnology.
Drug delivery systems that include biodegradable polymers, dendrimers, electroactive polymers are being studied. The results have yielded a fast degrading matrix that consists of a hydrophilic, amorphous, low-molecular- weight polymer that contain heteroatoms in its make up. This gives the researcher the ability to adjust the rate of its degradation, and therefore control the rate of drug delivery. Some of these have spokes coming out of the central core to which the biomolecules are attached and have the ability to hide the molecule from the immune system.
Bioengineers are exploring new strategies to find other innovative drug delivery systems. One new technology involve the use of dendrimers, these are highly branched, globular, synthetic macromolecules and buckyballs that will be used to deploy medications and is capable of moving drugs to targeted areas. The dendritic macromolecules make suitable carriers because their structure and sizes they can be controlled by synthetic means, they can also be processed and made biodegradable. The advantages of these are that they can hold small drug molecules, and can serve as recipients for large numbers high densities of drug molecules that can be transported to the affected areas. Researchers are also exploring ways to construct polymers that the body will not recognize as foreign. The polymer mielles is very tiny. It is only a tens of nanometers in diameter. Their size is ideal for enclosing individual drug molecules. Their outer shell of hydrophilic protect the contents of their inner core from the chemical reaction while they travel in the blood or plasma.. They finally release the drug after the degradation of the outer core.
It is not only in the area of drug delivery systems that that this new research is evident, but progress need to be made in areas such as: forced inhalation devices, transdermal methodologies, forced- pressure injectables, and biodegradable polymer networks that are designed specifically to transport new gene therapies; replacement parts for tissues and bones; artificial kidneys for patients with severe kidney diseases. Researchers also need to investigate the safety and efficacy of the current treatments, finding ways to administer injectable only medications orally, and making multiple dosage life long drug therapies in expensive, also needed are potent, time releasing or self triggering drug formulations. These new developments need to be cost effective and user friendly so that patients will be able to treat themselves.