Delivery Systems @ MMI
Delivery systems of various types are found in all areas of human activity and can range from delivering mail and information, to delivering passengers, energy, various substances, irradiation, etc. Of these, the delivery systems of special interest to polymer science, MMI and its sister organizations are the controlled-release systems which deliver either substance or irradiation in a controlled rate and at a targeted location. Such systems are needed in many different fields, including chemical industry, agriculture, cosmetics, hygiene, disinfection and decontamination, food industry, etc. However, in recent decades they have generated probably the most impact in pharmacology and medicine.
From ancient times of traditional healers, magicians and medicine men to present days of the 21st century biomedical sciences there has always existed a strong interest in delivery and sustained release of bioactive agents at the location of the ailment, but, until recently successes were limited to virtually only poultices and salves. An ideal pharmaceutical delivery system should provide the drug only when and where it is needed, at the appropriate concentration and for the predefined period of time required to achieve the desired therapeutic effect. In reality, however, this often reduces to achieving controlled, prolonged, timed, programmed or extended release of the substance, in concentrations which are above the minimum effective drug level but below the potentially toxic one. Additionally, such concentrations should be maintained relatively constant over the period of therapeutic time so that negative effects of concentration fluctuation between, under or over these limits, which are always present in repeated dose therapies, can be avoided.
Since the 1960s, polymers have been realized as ideal vehicles for such delivery systems. This is because they offer unique combinations of a number of properties that are essential for accomplishing this task, including their chemical compositions that can be non-toxic and non-irritant, solubility in aquatic systems and blood plasma, favorable combinations of molecular sizes and hydrophobicity which permit effective excretion through kidneys, rheological properties and molecular flexibility, ability to form films, sponges, sheets or membranes through which small molecules can diffuse at a controlled rate, ability to hydrolyze their chemical bonds to release attached substances at specific pH values and/or self-degrade into shorter segments that can be easier to excrete, etc. Utilizing specific combinations of some or all of such properties, the science of molecular engineering has produced in recent decades a number of controlled-release systems that have become more or less common healing tools of modern medicine. Some of these systems include polymeric drugs and polymeric drug carriers, biodegradable polymers, diffusional delivery systems (such as polymeric capsules and matrix-based devices), transdermal delivery systems, liposomal unilamelar vesicles, polymer-coated oral sustained release systems, osmotic and infusion pumps, etc.
At MMI, our interests in this area are focused primarily in two main directions: dendrimer-based targeted drug or irradiation delivery systems and specialty coatings that are capable of delivering active substances, as for example in antimicrobial protection. The former are of particular interest in cancer and gene therapy, while the later can find applications from household uses to hospitals, to public buildings and to the military. It is expected that the future of medical science is in selective drug targeting of specific sites in the body that need healing. This could lead to personalized medicine where every drug and every treatment will be specifically designed for a particular patient representing a completely new methodology with enormous advantages over the traditional ones and capability to completely change pharmacology and medicine as we know them. Such therapies would preclude transport of often very dangerous and toxic drugs (such as those used in chemotherapy) through the body and thus eliminate serious side effects that often arise from the toxicity of active substances used. Ideally, a targetable drug carrier should be able to find and penetrate or at least attach to the targeted cell(s) where it steadily delivers the drug without depositing it anywhere else in the body. With their nanoscopic, precisely controllable molecular sizes, chemical composition, flexible surface chemistry and pronounced encapsulation abilities, our polyamidoamine (PAMAM) dendrimers represent ideal candidates for such applicatrions.