Sequential polydepsipeptides as biodegradable carriers for drug delivery systems.

Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L-alanyl)n-gamma-ethyl L-glutamyl-L-lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n-Glu(OEt)-Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n-Glu(OEt)-Lac]. The resulting poly(Ala-Ala-Glu(OEt)-Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing-hormone-releasing hormone agonist des-Gly10-[D-Leu6]-LH-RH ethylamide (LH-RH agonist), was incorporated into a sequential poly(Ala-Ala-Glu(OEt)-Lac) carrier by the melt-pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend-type and sandwich-type formulations. The rate of in vivo release of LH-RH agonist from a blend-type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwich-type formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 +/- 14 micrograms/day).