Poly(lactic acid) (PLA) and its random copolymers with glycolide (PLG) were modified by grafting onto hydrophilic macromolecular backbones, such as poly(vinyl alcohol) (PVA), to increase both hydrophilicity and to manipulate the polymer structure. The resulting branched PVA-g-PLG offers the possibility to manipulate physico-chemical properties, such as molecular weight and glass transition temperature. The degradation and erosion rates required for continuous release of hydrophilic macromolecules differs significantly from linear PLG. Microspheres were prepared to investigate the release of hydrophilic dextran as a function of polymer structure. A reduction of the poly(lactic-co-glycolic acid) chain lengths in PVA-g-PLG caused a change in erosion profiles from bulk erosion to a surface front erosion mechanism, when the molecular weight of the PLG side chains was below 1000 g/mol, which is equal to water-solubility when cleaved from the backbone. Drug release rates from microspheres were significantly influenced by the polymer structure. A reduction of the PLG chain lengths led to increasing erosion controlled release rates, while an increase of the molecular weight of the core PVA resulted in a more diffusion controlled release mechanism. Release profiles could be adjusted over a broad range from ca. 14 days to 3 months. Ln combination with the possibility of avoiding accumulation of acidic breakdown products in the delivery device, PVA-g-PLG are of particular interest for parenteral delivery systems containing proteins, peptides or oligonucleotides. (C) 2000 Elsevier Science Ltd. All rights reserved.