MACROMOLECULAR PRODRUGS .2. ESTERS OF L-DOPA AND ALPHA-METHYLDOPA

L-Dopa and alpha-methyldopa were attached by an ester linkage to alpha ,beta-poly(N-hydroxyethYl)-DL-aspartamide (PHEA), a hydrophilic polyme r, previously proposed as a drug carrier. Ester bonding was achieved b y means of 1-benzotriazolylcarbonyl (Btc) group as both an N-protectin g and C-activating group in the starting amino acids. In the same way several simple esters Of L-dopa and alpha-methyldopa were prepared. Re lease of active substances based on hydrolysis of PHEA adducts was stu died in vitro, and the following (pseudo) first order release rate con stants for L-dopa and alpha-methyldopa were obtained, 1.06 X 10(-3) an d 6.91 X 10(-4) min-1, respectively. In addition, characterization of the PHEA-L-dopa adduct was carried out in vivo using an intracerebral microdialysis technique in order to evaluate the prolonged release eve ntually achieved.