10-hydroxycamptothecin-loaded starch-based microcapsules with the stepwise responsive release strategy for targeted...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Controlled drug release is crucial for effective cancer therapy, aiming to minimize toxicity to healthy tissues.
• Developing targeted delivery strategies enhances drug availability and therapeutic outcomes.
• Glutathione (GSH) and reactive oxygen species (ROS) are key biomarkers in the tumor microenvironment.

Purpose of the Study:

• To engineer novel glutathione (GSH)-responsive microcapsules (FA-RSMCs) for targeted delivery of 10-Hydroxycamptothecin (HCPT).
• To create a stepwise drug release system utilizing ROS-responsive polyprodrugs within the microcapsules.
• To evaluate the cascade-response release, anti-tumor efficacy, and safety of the developed delivery system in vitro.

Main Methods:

• Sonochemical preparation of thiolated modified starch-based microcapsules (FA-RSMCs).
• Design of a reactive oxygen species (ROS)-responsive polyprodrug (polyHCPT) loaded into microcapsules.
• In vitro evaluation of GSH- and ROS-triggered cascade drug release in a simulated tumor microenvironment.
• Assessment of in vitro cytotoxicity and anti-tumor activity.

Main Results:

• FA-RSMCs demonstrated successful GSH-responsive cleavage, releasing polyHCPT.
• PolyHCPT underwent subsequent ROS-responsive cleavage, releasing intact HCPT drug molecules.
• The system exhibited favorable cascade-response release properties in vitro.
• FA-RSMCs showed significant anti-tumor ability and protected normal cells in cytotoxicity assays.

Conclusions:

• The developed FA-RSMCs provide a promising strategy for stepwise drug release based on tumor microenvironment triggers.
• This targeted delivery system enhances the accuracy and safety of HCPT delivery for cancer therapy.
• The FA-RSMCs hold potential for future clinical applications in oncology.