title: Towards Hypoxia-responsive Drug-eluting Embolization Beads.
abstract: 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 release via ionic 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 an in vitro reducing environment.
authors.affiliation: School of Pharmacy & Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, United Kingdom; Biocompatibles UK Ltd, A BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, United Kingdom.
authors.forename: Koorosh
authors.initials: K
authors.lastname: Ashrafi
authors.affiliation: Biocompatibles UK Ltd, A BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, United Kingdom.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Heaysman
authors.affiliation: School of Pharmacy & Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, United Kingdom.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Phillips
authors.affiliation: School of Pharmacy & Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, United Kingdom.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lloyd
authors.affiliation: Biocompatibles UK Ltd, A BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, United Kingdom. Electronic address: andrew.lewis@btgplc.com.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D016461:Chemoembolization, Therapeutic; D004317:Doxorubicin / Q000008:administration & dosage; D065546:Drug Liberation; D020100:Hydrogels / Q000737:chemistry; D000860:Hypoxia; D008863:Microspheres
chemical_list: D000903:Antibiotics, Antineoplastic; D020100:Hydrogels; D004317:Doxorubicin
keywords: Bis(acryloyl)-(L)-cystine; Disulfide cross-linking; Drug-eluting beads; Hypoxia-responsive; Transarterial chemoembolization