Towards Hypoxia-responsive Drug-eluting Embolization Beads

Koorosh Ashrafi, C.L. Heaysman, Gary Phillips, Andrew Lloyd, Andrew Lewis

Research output: Contribution to journalArticlepeer-review


Drug release from chemoembolization microspheres stimulated by the presence of a chemically reducing environment may provide benefits for targeting drug resistant and metastatic hypoxic tumours. A water-soluble disulfide-based bifunctional cross-linker bis(acryloyl)-(l)-cystine (BALC) was synthesised, characterised and incorporated into a modified poly(vinyl) alcohol (PVA) hydrogel beads at varying concentrations using reverse suspension polymerisation. The beads were characterised to confirm the amount of cross-linker within each formulation and its effects on the bead properties. Elemental and UV/visible spectroscopic analysis confirmed the incorporation of BALC within the beads and sizing studies showed that in the presence of a reducing agent, all bead formulations increased in mean diameter. The BALC beads could be loaded with doxorubicin hydrochloride and amounts in excess of 300mg of drug per mL of hydrated beads could be achieved but required conversion of the carboxylic acid groups of the BALC to their sodium carboxylate salt forms. Elution of doxorubicin from the beads demonstrated a controlled releaseviaionic exchange. Some formulations exhibited an increase in size and release of drug in the presence of a reducing agent, and therefore demonstrated the ability to respond to anin vitroreducing environment.
Original languageEnglish
Pages (from-to)226-237
Number of pages12
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - 31 Mar 2017

Bibliographical note

© 2017 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license


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