Rate-controlled delivery systems in drug and hormone research.

Abstract

The advent of implantable devices that give long-duration control over the rate of drug or hormone administration in laboratory animals has opened up both novel and previously impractical experimental methods, protocols, and models for delivering these substances. This review brings together these new methods, protocols, and models for examination from the general perspectives of experimental pharmacology, toxicology, and physiology. They have origi­ nated in various specialized fields that infrequently cross-communicate, yet they have a common theme in the controlled deployment of bioactive agents in experimental animals. The novelty in this theme stems both from recent technological advances in drug delivery systems and from the ingenious ways in which individual researchers have put them to use. The focus here is on uses of delivery systems rather than on their technical aspects, which have been well-reviewed elsewhere (1, 2). Some history of the development of these delivery systems is pertinent, however. Only during the past two decades have practical means existed for multiday, rate-controlled administration of drugs or hormones to both experimental animals and man. Most of the technical advances in delivery systems for clinical use, including infusion pumps, have come since 1974. Among systems for research use, little progress was made with external pumps because of the intricacies of maintaining a leakand kink-proof flow path from a stationary pump to an uncooperatively revolving animal. An early development was the Rose-Nelson osmotic pump (3)-too bulky for rodents but small enough to be worn externally by dogs-allowing the first multiday infusions of angiotensin