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On-Demand Drug Release from Click-Refillable Drug Depots
Sandeep Palvai1, Christopher T Moody1,2, Sharda Pandit1,2
1Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Raleigh, North Carolina 27607, United States.
Molecular Pharmaceutics
|September 8, 2021
Summary
This study introduces a novel, noninvasive drug delivery system using bioorthogonal click chemistry and light-triggered release for on-demand cancer therapy. The system allows for repeated refilling of drug depots, enhancing treatment potential.
Area of Science:
- Biomedical Engineering
- Drug Delivery Systems
- Nanotechnology
Background:
- Conventional drug depots require invasive procedures for refilling or replacement.
- On-demand drug release offers precise local dosing for targeted therapies.
- Existing methods lack noninvasive refilling capabilities for sustained treatment.
Purpose of the Study:
- To develop a novel, noninvasive, on-demand drug delivery system.
- To enable repeated refilling and light-triggered drug release from localized depots.
- To demonstrate the efficacy of this system for targeted cytotoxic drug delivery.
Main Methods:
- Utilized bioorthogonal click chemistry to anchor azide groups to the extracellular matrix, forming a targetable depot.
- Developed a photoresponsive protodrug (doxorubicin conjugated to DBCO via a photocleavable linker).
- Administered protodrug intravenously and triggered drug release using external light irradiation in vitro and in vivo.
Main Results:
- Successfully formed stable azide depots in mice.
- Demonstrated specific protodrug capture by azide depots with potential for multiple refills.
- Achieved on-demand, light-triggered release of doxorubicin with in vitro cytotoxicity.
- Showcased successful multiple rounds of depot refilling and drug release in vivo.
Conclusions:
- Established a novel in vivo drug targeting and on-demand delivery system.
- The developed system allows for noninvasive refilling and repeated, light-triggered drug release.
- This approach holds significant potential for localized, sustained, and repeatable cancer therapy.