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

• Published in: Carbohydrate polymers Vol. 171; pp. 220 - 228
• Main Authors: Huerta-Angeles, Gloria, Brandejsová, Martina, Nigmatullin, Rinat, Kopecká, Kateřina, Vágnerová, Hana, Šmejkalová, Daniela, Roy, Ipsita, Velebný, Vladimír
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-09-2017
• Subjects: Esterification; Graft copolymers; Hyaluronan; Hydrolysis; Polyhydroxyalkanoates; Graft copolymers; P(3HO-3HD); P(3HO); CDI; 3T3-NIH; SEC-MALLS; MTT; HSTU; Esterification; Hydrolysis; DOSY; TEA; Hyaluronan; Resveratrol (PubChem CID: 445154); DSC; P(3HO-3HD-3HDD); DMAP; Sodium hyaluronate (PubChem CID: 53447380); Curcumin (PubChem CID: 101736865); IPA; P(3HB); HSQC; Polyhydroxyalkanoates; HPLC
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2017.05.011

•Joining two natural motifs: hyaluronan (HyA) and poly(3-hydroxyalkanoates) (PHAs).•Hydrolysis of PHAs yielded oligomers suitable for HyA covalent grafting.•1,1, Carbonyldiimidazole allowed hyaluronan modification under mild conditions.•Water soluble copolymers as potential carriers for drug delivery.
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.