Synthesis of Polylactide-grafted Dextran and Their Application as Biodegradable Biomedical Materials

Biodegradable, biocompatible polymers are of interest for use in several biomedical and pharmaceutical applications. Based on its biodegradability, biocompatibility, high mechanical strength, and good shaping and molding properties, polylactide (PLA) is frequently utilized as an implantable carrier for drug delivery systems, as well as a surgical repair material. However, its high crystallinity interferes with predictable degradation, reduces its compatibility with soft tissues and presents an obstacle to its application as a biodegradable soft plastic. One promising approach to overcoming these problems in PLA is the introduction of hydrophilic segments and branched structures. On the other hand, polysaccharides are natural, biodegradable and hydrophilic polymers that can be degraded enzymatically and possess relatively good biocompatibility, but are insoluble in common organic solvents. PLA is commonly synthesized by a ring-opening polymerization of lactic acid dimer (lactide, LA). The anionic ring-opening polymerization reaction of LA is performed in the presence of an alkali metal alkoxide to give PLA having the alkoxide used on the end. Our group has succeeded in obtaining graft copolymers consisting of PLA and polysaccharides using partially trimethylsilyl (TMS)-protected polysaccharides as initiators and subsequent removal of TMS groups. Using dextran as a polysaccharide, the obtained PLA-grafted dextran (Dex-g-PLA) (Fig. 1) films were found to have lower values of Tg, Tm, crystallinity, and a higher viscosity compared with poly-L-lactide (PLLA) films due to the introduction of polysaccharide segments and branched structures into PLLA. Properties of Dex-g-PLA can be varied by controlling of the molecular structure: length and number of graft chains, and proportion of hydrophilic to hydrophobic segments in the graft copolymers. In fact, degradation rates strongly depended on the content of polysaccharide. In this presentation, to explore the possibility of Dex-g-PLA as a new biodegradable soft-biomaterial, preliminary investigations were carried out for the effect of molecular structure of Dex-g-PLA on the surface properties and cell attachment behavior of the films prepared from the copolymers. Moreover, Dex-g-PLA has amphiphilic structure and should be useful drug release depot for hydrophilic macromolecules (proteins, nucleic acids). So we also report on the preparation of protein (BSA, bovine serum albumin)-loaded microspheres (MSs) from Dex-g-PLA.