Protein delivery with infusion pumps.

When a therapeutic effect is optimized by precise control of specific temporal patterns of plasma levels, infusion offers distinct advantages over oral administration, bolus injection, or depot delivery of polypeptides. The limitations of oral delivery are well known, and although research is under way into development of carrier systems that prevent degradation of labile agents, it is unlikely that the variances in absorption will meet the need for precise control. Depot delivery from subcutaneous or intramuscular implants presents a difficult situation when local tissue reactions to the agent sometimes occur. Removal of a depot system in the event of adverse reactions presents additional difficulties. Bolus injections are unable to sustain constant plasma levels unless the drug half-life is long or the injections are frequently administered. Insulin injections, for example, would be required every 30-60 minutes to approximate the plasma levels provided by a continuous infusion; such frequent injections would not be practical on a 24-hour basis. For the developer of new polypeptides, parenteral administration offers the most direct route to the marketplace. The step from periodic injections to tightly controlled infusion is a logical progression as compared with modification of the molecules or vehicles to obtain equivalent profiles. In Table II several different types of devices that can be used for infusion of proteins are compared. Microelectronics have played a major role in the miniaturization of infusion devices and undoubtedly will continue to do so. Micromachining, a spin-off technology of integrated circuit manufacture, will also find application in small infusion devices. In the future, we will have cost-effective disposable devices (Saaman et al., 1994) built on this technology that are programmable and thus can be adapted to meet each individual therapeutic need (Horres, 1994). We can also expect to see more closed-loop drug delivery systems where biosensors and infusion devices are combined to optimize a particular therapy. Recent positive results obtained in diabetics by a decade on tight glucose control may forecast a resurgence of popularity of insulin pumps. At the other end of the spectrum, low-cost, small, and simple-to-use osmotically powered systems are close to being marketed; these systems will make infusion almost as convenient as transdermal patches. We will also see major advances in how drugs and devices are interfaced. Prefilled and ready-to-use drug cartridges have proven to be efficient in surgical and emergency medicine and can greatly improve most infusion applications. It is anticipated that coded, prefilled cartridges or pouches will be automatically, recognized by preprogrammed pumps to reduce operator labor and entry error.