Injectable sustained local release doxorubicin depot technology- a promising adjuvant to systemic treatment?

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Oncology

Background:

• Local chemotherapy delivery aims to maximize efficacy while minimizing systemic toxicity.
• Drug depot technologies offer sustained release of chemotherapeutics directly at the tumor site.
• Carbohydrate-ester-based formulations represent a novel approach for injectable drug depots.

Purpose of the Study:

• To assess the feasibility, delivery capacity, and therapeutic efficacy of a thin needle injectable doxorubicin-loaded carbohydrate-ester-based (CarboCell) depot.
• To evaluate the release kinetics and biodistribution of doxorubicin from CarboCell depots.
• To determine the anti-tumoral activity and survival benefit of CarboCell in a colorectal cancer model.

Main Methods:

• CarboCell release kinetics were assessed in non-tumorous mice after subcutaneous injection.
• Therapeutic efficacy was evaluated in CT 26 colorectal cancer mice via intratumoral injections of doxorubicin-loaded CarboCell.
• Doxorubicin distribution and systemic exposure were analyzed in pigs using microdialysis after injection into the tibial metaphysis.

Main Results:

• Subcutaneous CarboCell depots showed sustained doxorubicin release, with 36% at 24h and 48% at 48h.
• Intratumoral CarboCell injections effectively controlled tumor growth and significantly extended median survival time.
• In pigs, doxorubicin concentrations exceeded 0.3 µg/mL up to 10mm from the injection site in the metaphysis with minimal systemic spill-over.

Conclusions:

• Doxorubicin-loaded CarboCell is an easily administrable injectable depot technology.
• CarboCell demonstrates sustained local drug release, effective anti-tumoral activity, and favorable biodistribution.
• The technology provides high local drug concentrations in metaphyseal bone with limited systemic exposure, indicating therapeutic potential.