Controlled delivery of indomethacin with poly (DL-Glu-Co-DL-Leu) as a biodegradable carrier

Abstract

Many efforts have been made to investigate the polymeric drug delivery system in which polymeric material is employed as a carrier of a drug to deliver the drug to a specific body site at effective therapeutic range over a desired time period, thereby reducing the toxic or side effects and improving the effectiveness of therapy. Of many types of the polymeric drug delivery systems so far known, the biodegradable drug delivery system has some advantage over others in that it is free from the problem of retrieval of the exhausted device by a surgical operation. In this research, problems on the application of the biodegradable copolymer of glutamic acid and leucine to a potent antiinflammatory agent, indomethacin, were studied. The release rate of indomethacin, after the intense burst effect, found to be increased with the increasing amount of leucine residue in the polymer. Since the density of the polymer was inversely related to the content of the leucine residue, it was suggested that the release rate of indomethacin would be higher in the case of the polymer with lower density. The release rate of indomethacin was also increased with decreasing pH of the releasing media, and this phenomenon was thought to result from the change in the polymer conformation and from the change in solubility of indomethacin along the pH change. Moreover, the common burst effect could not be noted at pH 3.0. The duration of the drug delivery system and the lifespan of the polymer was shorter in the case of the polymer with higher content of glutamic acid residue. It occurred that this result could be related to the increased rate of hydrolysis of the polymer in which the content of the glutamic acid residue was higher and thus whose hydrophilicity was greater. Use of bovine serum, instead of the buffer, as the releasing medium slightly decreased the duration of the delivery system, but the lifespan of the polymer was increased. Considering all the requirements as a carrier o...