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β-Lactamase-Responsive Hydrogel Drug Delivery Platform for Bacteria-Triggered Cargo Release
Dahlia Alkekhia1, Cassi LaRose1, Anita Shukla1
1School of Engineering, Center for Biomedical Engineering, Brown University, Providence, Rhode Island 02912, United States.
ACS Applied Materials & Interfaces
|June 8, 2022
Summary
Researchers developed novel hydrogels that degrade upon encountering beta-lactamase enzymes and bacteria. This breakthrough enables targeted drug delivery, potentially reducing antibiotic resistance by controlling antimicrobial release during infection treatment.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Antimicrobial Resistance Research
Background:
- Antibiotic resistance is a significant global health challenge, often driven by bacterial enzymes like beta-lactamases.
- Effective treatment of bacterial infections is hindered by the widespread production of beta-lactamases, which inactivate common antibiotics.
- There is a critical need for innovative drug delivery systems that can specifically target infections and minimize the development of further resistance.
Purpose of the Study:
- To engineer hydrogels that degrade specifically in response to beta-lactamase enzymes and bacteria.
- To create a platform for bacteria-triggered drug delivery, enabling controlled release of therapeutic agents.
- To investigate the potential of these responsive hydrogels in combating antibiotic resistance.
Main Methods:
- Hydrogels were synthesized using a maleimide-functionalized, beta-lactamase-cleavable cephalosporin as a crosslinker.
- Polymerization was achieved via Michael-type addition with multiarm thiol-terminated poly(ethylene glycol) macromers.
- Degradation studies were performed in vitro with purified beta-lactamases and beta-lactamase-producing bacteria, as well as in an ex vivo porcine skin infection model.
Main Results:
- Responsive hydrogels successfully degraded in the presence of beta-lactamases and bacteria, while non-responsive hydrogels remained stable.
- Encapsulated nanoparticles were released from the hydrogels at rates correlating with hydrogel degradation, demonstrating controlled cargo release.
- The responsive hydrogels showed stability against other enzymes like collagenases and lipases, indicating specificity.
Conclusions:
- Developed hydrogels offer a specific, bacteria-triggered drug release mechanism.
- This technology has the potential to enhance infection treatment efficacy while mitigating the exacerbation of antibiotic resistance.
- The hydrogels represent a promising platform for targeted antimicrobial delivery systems.
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