Controlled release of doxorubicin from pH-responsive microgels

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Stimuli-responsive hydrogels offer targeted drug delivery solutions by responding to physiological cues like pH and temperature.
• Doxorubicin (DOX) is a potent anti-cancer drug, but its systemic toxicity necessitates controlled delivery strategies.
• Optimizing anti-tumor efficacy while minimizing side effects is crucial for effective cancer chemotherapy.

Purpose of the Study:

• To develop pH-responsive microgels for enhanced doxorubicin (DOX) delivery.
• To investigate the influence of formulation parameters on microgel properties and drug release kinetics.
• To evaluate the anti-tumor activity of DOX delivered via the developed microgels.

Main Methods:

• Fabrication of pH-responsive microgels using a copolymer of oligo(polyethylene glycol) fumarate (OPF) and sodium methacrylate (SMA).
• Characterization of microgel charge, pH, and ionic strength sensitivity.
• Loading and in vitro release studies of DOX from the microgels.
• Development of a mathematical model to analyze DOX release profiles.
• Assessment of anti-tumor activity using a human chordoma cell line.

Main Results:

• OPF-SMA microgels demonstrated pH and ionic strength sensitivity, with charge density correlating to SMA concentration.
• Efficient loading and controlled release of DOX via an ion-exchange mechanism were achieved.
• DOX release kinetics were modulated by solution pH and ionic strength.
• A phenomenological model showed a linear correlation between maximum DOX release and SMA concentration.
• OPF-SMA microgels prolonged the cytotoxic effect of DOX against human chordoma cells.

Conclusions:

• OPF-SMA microgels represent a promising platform for pH-triggered, controlled doxorubicin delivery.
• The developed microgels can potentially improve anti-tumor efficacy and reduce systemic toxicity of DOX.
• The study provides a quantitative understanding of DOX release and its correlation with microgel formulation.