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Dosing and Delivery of Bacteriophage Therapy In a Murine Wound Infection Model
Yung-Hao Lin1, Tejas Dharmaraj2, Qingquan Chen2
1Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
Biorxiv : the Preprint Server for Biology
|May 20, 2024
Summary
Topical phage therapy, using high doses and repeated application, effectively treats wound infections. A novel hydrogel system, HydroPhage, enhances this delivery for better bacterial eradication.
Area of Science:
- Microbiology
- Biotechnology
- Infectious Diseases
Background:
- Lytic bacteriophages show potential for treating bacterial infections, especially those caused by antibiotic-resistant strains like *Pseudomonas aeruginosa*.
- Optimal phage therapy strategies, including dosing and delivery, require further investigation for clinical application.
Purpose of the Study:
- To evaluate the impact of phage dose, frequency, and administration route on the efficacy of phage therapy against *Pseudomonas aeruginosa* wound infections in a mouse model.
- To develop and assess a novel hydrogel-based delivery system for sustained phage release.
Main Methods:
- A mouse wound infection model was used to test different phage therapy parameters (dose, frequency, route).
- A hyaluronan-based hydrogel (HydroPhage) was developed for sustained, high-titre phage delivery.
- Efficacy was measured by bacterial burden reduction and infection eradication rates.
Main Results:
- Topical phage administration was effective, while intravenous delivery was not in this model.
- Higher phage doses and repeated dosing significantly improved bacterial eradication.
- HydroPhage demonstrated superior efficacy, eradicating infections five times more effectively than intravenous injection.
Conclusions:
- Sustained topical delivery of bacteriophages via hydrogel enhances therapeutic efficacy.
- HydroPhage offers a practical and well-tolerated approach for treating wound infections.
- Optimized phage delivery strategies are crucial for effective phage therapy.
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