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Towards Hypoxia-responsive Drug-eluting Embolization Beads.
Koorosh Ashrafi1, Clare L Heaysman2, Gary J Phillips3
1School 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.
International Journal of Pharmaceutics
|April 5, 2017
Summary
New chemoembolization microspheres using bis(acryloyl)-(l)-cystine (BALC) respond to reducing environments, offering potential for drug-resistant and hypoxic tumors. These BALC-crosslinked poly(vinyl) alcohol beads show controlled drug release and swelling in vitro.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Oncology Therapeutics
Background:
- Hypoxic tumors, common in drug-resistant and metastatic cancers, present a significant challenge in chemotherapy.
- Chemoembolization microspheres offer localized drug delivery, but controlled release mechanisms tailored to tumor microenvironments are needed.
Purpose of the Study:
- To synthesize and characterize a novel disulfide-based cross-linker, bis(acryloyl)-(l)-cystine (BALC), for stimuli-responsive hydrogel microspheres.
- To investigate the incorporation of BALC into poly(vinyl) alcohol (PVA) hydrogel beads and evaluate their drug loading and release characteristics.
- To assess the responsiveness of BALC-modified microspheres to a reducing environment for targeted drug delivery.
Main Methods:
- Synthesis and characterization of bis(acryloyl)-(l)-cystine (BALC).
- Preparation of poly(vinyl) alcohol (PVA) hydrogel beads cross-linked with BALC via reverse suspension polymerization.
- Characterization of BALC incorporation, bead swelling, doxorubicin hydrochloride loading, and in vitro drug release studies under reducing conditions.
Main Results:
- BALC was successfully synthesized and incorporated into PVA hydrogel beads, confirmed by elemental and spectroscopic analysis.
- Bead formulations showed increased diameter in the presence of a reducing agent, indicating environmental responsiveness.
- High loading capacity for doxorubicin hydrochloride was achieved after converting BALC's carboxylic acid groups to sodium carboxylate salts.
- Controlled, ionic-exchange-based drug elution was observed, with some formulations releasing drug in response to reducing agents.
Conclusions:
- BALC-crosslinked PVA hydrogel microspheres are stimuli-responsive materials suitable for chemoembolization.
- These microspheres demonstrate potential for targeted drug delivery to hypoxic tumors by responding to the reducing tumor microenvironment.
- The ability to control drug release based on environmental cues offers a promising strategy for overcoming drug resistance in cancer therapy.