Robert V. Petersen

Biodegradable Drug Delivery Systems Based on Polypeptides

A new dimension to the use of polymeric materials as drug delivery devices is the incorporation of biodegrability into the system. A number of degradable polymers are potentially useful for this purpose, including synthetic and natural substances. A number of such substances are described in this chapter. However, major emphasis is placed on synthetic poly(α-amino acids). These polymers are useful for matrix and reservoir-type delivery systems and, in addition, when difunctional amino acids, such as glutamic acid, are utilized, polymer/drug conjugates represent another new dimension. In polymer/drug conjugates, the drug is covalently bonded directly to the polymeric “backbone” or to a spacer group between the drug and polymer. The bond must be of a type which hydrolyzes more rapidly than the amide bonds in the polymeric backbone. A number of such conjugates have been synthesized and evaluated for in vitro and in vivo hydrolysis and for potential toxicity. It appears that this concept can be utilized to advantage in the development of delivery systems for a wide variety of bioactive substances.

METABOLISM AND AUTORADIOGRAPHIC LOCALIZATION OF DI-2-ETHYLHEXYL PHTHALATE (DEHP) IN MICE AND A MODEL ECOSYSTEM

Publisher Summary Di-2-ethylhexyl phthalate (DEHP) is the most widely used plasticizer for vinyl plastics. It is estimated that 350 million pounds was produced in the United States during 1970. The cumulative production of DEHP and related phthalate plasticizers in the United States since 1943 was in excess of 8 billion pounds. A recent technical conference on plastics indicated there is continued growth of the vinyl plastics industry in the future. Plastics have been identified in remote areas of the world such as the Western Sargasso Sea to familiar river systems in the United States. The presence of phthalates in fish—suggesting a potential link in the food chain to man—has been reported. DEHP has also begun to appear as a micropollutant in the tissues of warm-blooded animals, including man. It has been found in bovine pineal glands, mitochondria from the hearts of cattle, spleen, liver, lung and abdominal fat of humans in quantities ranging from 25 ppm in the spleen to 270 ppm in the abdominal fat. The high titer reported in fat is because of the fact that DEHP has a high fat solubility and low water solubility. DEHP has all of the requisite properties to be classified as a potential environmental and physiological micropollutant.

LEACHABLE COMPONENTS AND BIOCOMPATABILITY OF PVC MEDICAL DEVICES

Publisher Summary The use of polymeric materials as components of medical and dental prostheses and devices has increased exponentially over the past decade. The need for suitable materials for use in artificial organs, blood collection, storage and administration assemblies, extracorporeal circulation devices of the type used during cardiopulmonary bypass and renal hemodialysis procedures, and for other medically oriented applications has stimulated research on the acceptability of existing materials for these applications and on the synthesis of novel candidate materials. Polyvinyl chloride, (PVC), a polymer that has been known and used for many years, is one of the most widely used plastics in medical devices. Pure PVC is a hard, brittle material. However, when plasticizers, such as esters of phthalic, citric, maleic, sebacic, adipic, or other acids are added, it becomes soft and flexible. Compounded PVC contains numerous other additives. Heat stabilizers are usually organometallic compounds and generally consist of organic esters containing tin, cadmium, barium, calcium, or zinc, or combinations of these cations. PVC tubing for blood transfusion and catheter applications requires nontoxic stabilizers based on zinc or calcium. Other PVC additives include antioxidants, fillers, pigments, lubricants, and other compounds added for specific reasons.