Doxorubicin-Loaded Polymeric Meshes Prevent Local Recurrence after Sarcoma Resection While Avoiding Cardiotoxicity

Area of Science:

• Biomaterials Science
• Surgical Oncology
• Pharmacology

Background:

• Soft-tissue sarcomas, particularly in the retroperitoneum, have high recurrence rates (35-59%) even after surgical resection.
• Systemic chemotherapy with Doxorubicin (DOX) for advanced sarcomas has limited efficacy and causes dose-limiting cardiotoxicity.

Purpose of the Study:

• To develop and optimize a novel drug delivery system for localized treatment of soft-tissue sarcomas.
• To evaluate the efficacy and safety of a Doxorubicin-loaded surgical mesh in preventing tumor recurrence and cardiotoxicity.

Main Methods:

• Fabrication of an electrospun poly(caprolactone) (PCL) surgical mesh coated with poly(glycerol monostearate-co-caprolactone) (PGC-C18).
• Loading the mesh with Doxorubicin (DOX) for direct delivery to the tumor bed post-resection.
• Testing the DOX-loaded meshes (DoM) in xenograft models of liposarcoma and chondrosarcoma.

Main Results:

• DoM significantly increased overall survival by 4-fold compared to systemic DOX in animal models.
• Local recurrence was prevented in nearly all animals treated with DoM.
• Mice receiving DoM maintained normal cardiac function, while systemic DOX administration led to a 23% decrease in cardiac output and ejection fraction.

Conclusions:

• The developed DOX-loaded mesh (DoM) represents a feasible approach for preventing post-surgical sarcoma recurrence.
• This localized delivery method effectively minimizes Doxorubicin-induced cardiotoxicity.
• This strategy offers a promising therapeutic option for soft-tissue sarcoma patients.