A new biodegradable polydepsipeptide microsphere for application in drug delivery systems

Abstract

A sequential polydepsipeptide containing a tripeptide sequence L-alanyl-Lalanylγ-ethyl L-glutamyl and anα-hydroxy acid L-lactic acid, poly(Ala-Ala-Glu(OEt)-Lac), was synthesized to prepare the microspherical particles by the solvent evaporation process. In this case, the solvents play the most important role for the preparation of polydepsipeptide microspheres and, as an example, when 200 mg of the polydepsipeptide dissolved in 10 ml of 98/2% chloroform/dichloroacetic acid mixture was stirred at 400 rpm and 30 ‡C, the microspherical particles with mean diameter of 58Μm were formed after pouring into 200 ml of 1% (w/v) poly(vinyl alcohol) solution. 17Β-Estradiol was incorporated into the particles, and the resulting particles were found to contain 5 mg of drug per 25 mg of the particle. The in vivo release of drug from the microspherical formulation was evaluated by measuring the pharmacological influence on rat prostate. It was found that the sufficient amount of drug, kee** the effective pharmacological influence, is supplied during the first 12-week period, followed by an incomplete supplying of drug intil the implant is perfectly degraded in vivo in the 25th week from the start of implantation.