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Related Experiment Videos

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
PubMed
Summary

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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).
Keywords:
Bis(acryloyl)-(L)-cystineDisulfide cross-linkingDrug-eluting beadsHypoxia-responsiveTransarterial chemoembolization

Related Experiment Videos

  • 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.