ULTRASOUND INDUCED DELIVERY OF PEPTIDES

Peptides and proteins are emerging as an increasingly important class of drugs as they become more readily available through improvements in recombinant DNA technology and chemical synthesis techniques. The application of peptides and proteins as clinically useful drugs is, however, seriously hampered due to substantial delivery problems. Peptides are readily degraded by enzymes, absorb poorly through the gastrointestinal track and have relatively short half lives once they reach the blood stream. A potentially useful approach to solve these delivery problems are the polymeric controlled delivery systems. Peptide delivery patterns can be further optimized by regulated delivery, adjusted to the staging of biological rhythms. In recent years several research groups have been developing responsive systems which would more closely resemble the normal physiological process in which the amount of drug released can be affected according to physiological needs. This paper discusses polymeric systems capable of delivering peptides, proteins and other agents at increasing rates on demand by an external ultrasound irradiation. Nondegradable, diffusion controlled, and degradable, erosion controlled polymers have shown enhanced kinetics of release when exposed to ultrasonic energy. Increased release rates where observed when ultrasound was applied to polymeric delivery systems implanted in rats. The effect of ultrasound on biological (skin) and synthetic membrane permeabilities was also evaluated. The mechanism elucidating the enhancing effect of ultrasound is discussed.