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Featured Article: Chemotherapeutic delivery using pH-responsive, affinity-based release.

Erika L Cyphert1, Andrew S Fu1, Horst A von Recum1

  • 1Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44118, USA.

Experimental Biology and Medicine (Maywood, N.J.)
|February 10, 2017
PubMed
Summary
This summary is machine-generated.

This study developed a novel drug delivery system for doxorubicin (DOX) that targets tumors. The modified DOX releases specifically in low-pH tumor environments, reducing systemic toxicity and maintaining cancer-killing effectiveness.

Keywords:
DoxorubicinadamantanecyclodextrinhydrazonepH-sensitive

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Area of Science:

  • Biomedical Engineering
  • Drug Delivery Systems
  • Oncology

Background:

  • Systemic administration of doxorubicin (DOX) causes significant cardiac and hepatic toxicities.
  • Local drug delivery aims to mitigate these side effects by concentrating chemotherapy at the tumor site.
  • Tumor-specific drug release mechanisms are crucial for enhancing efficacy and reducing off-target damage.

Purpose of the Study:

  • To develop a novel affinity-based drug delivery platform for doxorubicin (DOX).
  • To engineer DOX for pH-sensitive release within the acidic tumor microenvironment.
  • To evaluate the efficacy and release profile of modified DOX in vitro.

Main Methods:

  • Modification of doxorubicin with an adamantane group via a pH-sensitive hydrazone bond.
  • Incorporation of adamantane-doxorubicin into an affinity-based drug delivery polymer (cyclodextrin).
  • In vitro assessment of drug release kinetics at varying pH levels and cytotoxicity against U-87 glioblastoma cells.

Main Results:

  • The adamantane-modified doxorubicin exhibited high affinity for the delivery polymer with minimal release at neutral pH.
  • Accelerated drug release was observed in acidic, tumor-like conditions (pH 5.5).
  • Adamantane-doxorubicin demonstrated equivalent in vitro cytotoxicity to unmodified doxorubicin against U-87 glioblastoma cells.

Conclusions:

  • This affinity-based system enables high loading and controlled, localized release of modified doxorubicin.
  • The pH-sensitive hydrazone bond ensures drug release predominantly in the acidic tumor microenvironment.
  • The platform offers a promising strategy to reduce systemic toxicity of doxorubicin through enhanced local delivery.