Toward Drug Release Using Polymer Mechanochemical Disulfide Scission

Area of Science:

• Polymer Chemistry
• Materials Science
• Pharmacology

Background:

• Traditional pharmacotherapy faces challenges like antibiotic resistance and systemic toxicity.
• Current drug delivery systems often rely on external stimuli like heat or light.
• Mechanical force has not been extensively explored as a stimulus for drug release.

Purpose of the Study:

• To develop a novel mechanochemically responsive polymer system for controlled drug release.
• To utilize ultrasound as an external stimulus for polymer scission and drug activation.
• To demonstrate the release of furan-containing molecules, including drugs, via polymer mechanochemistry.

Main Methods:

• Design and synthesis of disulfide-centered polymers.
• Ultrasound-induced polymer scission to generate thiol-terminated polymers.
• Michael-type addition of thiol-terminated polymers to Diels-Alder adducts.
• Retro Diels-Alder reaction for downstream drug release.

Main Results:

• Successful ultrasound-induced cleavage of disulfide bonds in the polymer backbone.
• Demonstrated release of furan-containing molecules, including dansyl, furosemide, and furylated doxorubicin.
• Established a mechanism involving Michael addition followed by retro Diels-Alder reaction for drug release.

Conclusions:

• The developed system provides a new platform for mechanochemically controlled drug delivery.
• This approach offers precise control over drug release using mechanical force (ultrasound).
• The method serves as a blueprint for activating various small molecules through polymer mechanochemistry.