Tissue-reactive drugs enable materials-free local depots

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Oncology

Background:

• Local, sustained drug delivery offers targeted treatment for diseases, minimizing systemic side effects.
• Conventional drug depots (hydrogels, implants) face limitations in stiff tissues like desmoplastic tumors.
• A need exists for innovative drug delivery methods that can effectively function within challenging tumor microenvironments.

Purpose of the Study:

• To introduce Tissue-Reactive Anchoring Pharmaceuticals (TRAPs) as a material-free approach for creating intratumoral drug depots.
• To demonstrate the efficacy of TRAPs in achieving sustained drug release and enhanced therapeutic outcomes within tumors.
• To overcome the limitations of existing injectable depots in stiff and desmoplastic tumor tissues.

Main Methods:

• TRAPs were developed by modifying potent drugs with ECM-reactive groups for local tissue anchoring.
• TRAPs were locally injected into mouse and human pancreatic tumor tissues to form stable, dispersed intratumoral depots.
• TRAP paclitaxel was evaluated for solubility, in vitro/in vivo drug release kinetics, tumoral apoptosis, and antitumor efficacy compared to free paclitaxel.

Main Results:

• Locally injected TRAPs successfully formed stable, dispersed intratumoral depots within mouse and human pancreatic tumors.
• TRAP paclitaxel exhibited improved solubility and sustained drug release both in vitro and in vivo.
• TRAP paclitaxel treatment resulted in increased tumoral apoptosis and superior antitumor efficacy compared to free paclitaxel.

Conclusions:

• TRAPs provide a material-free method for sustained intratumoral drug delivery, overcoming limitations of traditional depots in stiff tissues.
• This approach enables continuous drug access to tumor cells, offering a promising strategy for localized diseases.
• TRAPs have broad potential for treating various diseases where current injectable drug delivery systems are inadequate.