Format

Send to

Choose Destination
Int J Pharm. 2017 May 30;524(1-2):226-237. doi: 10.1016/j.ijpharm.2017.03.084. Epub 2017 Mar 31.

Towards Hypoxia-responsive Drug-eluting Embolization Beads.

Author information

1
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.
2
Biocompatibles UK Ltd, A BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, United Kingdom.
3
School of Pharmacy & Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ, United Kingdom.
4
Biocompatibles UK Ltd, A BTG International Group Company, Lakeview, Riverside Way, Watchmoor Park, Camberley, GU15 3YL, United Kingdom. Electronic address: andrew.lewis@btgplc.com.

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.

KEYWORDS:

Bis(acryloyl)-(L)-cystine; Disulfide cross-linking; Drug-eluting beads; Hypoxia-responsive; Transarterial chemoembolization

PMID:
28373099
DOI:
10.1016/j.ijpharm.2017.03.084
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center