Synthesis of graft copolymers based on hyaluronan and poly(3-hydroxyalkanoates)

Abstract This work reports the synthesis and characterisation of new amphiphilic hyaluronan (HA) grafted with poly(3-hydroxyalkanoates) (PHAs) conjugates. Hydrolytic depolymerisation of PHAs was used for the synthesis of defined oligo(3-hydroxyalkanoates)-containing carboxylic terminal moieties. A kinetic study of the depolymerisation was followed to prepare oligomers of required molecular weight. PHAs were coupled with hydroxyl groups of HA mediated by N , N ′-carbonyldiimidazole (CDI) or HSTU Tetramethyl- O -( N -succinimidyl) uronium hexafluorophosphate. For the first time, the covalent bonding of oligo derivatives of P (3-hydroxybutyrate), P (3-hydroxyoctanoate), P ( 3-hydroxyoctanoate-co-3-hydroxydecanoate ) and P ( 3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate ) and HA was achieved by “grafting to” strategy. Achieved grafting degree was a function of hydrophobicity of PHA, Mw and polarity of the solvent. The most suitable reaction conditions were observed for oligo (3-hydroxybutyrate) grafted to HA (grafting degree of 14%). Graft copolymers were characterized by FT-IR, NMR, DSC and SEC-MALLS. Graft copolymers can be physically loaded with hydrophobic drugs and may serve as drug delivery system.