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

Gloria Huerta-Angeles; Martina Brandejsová; Rinat Nigmatullin; Kateřina Kopecká; Hana Vágnerová; Daniela Šmejkalová; Ipsita Roy; Vladimír Velebný

doi:10.1016/j.carbpol.2017.05.011

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

Carbohydr Polym. 2017 Sep 1:171:220-228. doi: 10.1016/j.carbpol.2017.05.011. Epub 2017 May 4.

Authors

Gloria Huerta-Angeles¹, Martina Brandejsová², Rinat Nigmatullin³, Kateřina Kopecká², Hana Vágnerová², Daniela Šmejkalová², Ipsita Roy³, Vladimír Velebný²

Affiliations

¹ Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic. Electronic address: huerta-angeles@contipro.com.
² Contipro a.s., Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
³ Department of Life Science, Faculty of Science and Technology, University of Westminster, 115 New Cavendish Street, London W1W 6UW, United Kingdom.

PMID: 28578957
DOI: 10.1016/j.carbpol.2017.05.011

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.

Keywords: Curcumin (PubChem CID: 101736865); Esterification; Graft copolymers; Hyaluronan; Hydrolysis; Polyhydroxyalkanoates; Resveratrol (PubChem CID: 445154); Sodium hyaluronate (PubChem CID: 53447380).