Local gentamicin delivery from resorbable viscous hydrogels is therapeutically effective

Area of Science:

• Biomaterials Science
• Infectious Disease Research
• Drug Delivery Systems

Background:

• Local antimicrobial delivery is crucial for treating biofilm-related infections.
• Existing resorbable carriers have slow degradation, while hydrogels offer faster degradation but rapid drug release.
• Previously developed PNDJ hydrogels provide sustained delivery over days and degrade within six weeks.

Purpose of the Study:

• To determine the gentamicin elution profile from PNDJ hydrogels.
• To evaluate the efficacy of gentamicin-loaded PNDJ (G-PNDJ) hydrogel in treating orthopedic infections.
• To assess potential renal dysfunction from local gentamicin delivery via G-PNDJ hydrogel.

Main Methods:

• Two G-PNDJ formulations (1.61 wt% and 3.14 wt%) were tested for gentamicin elution.
• Orthopedic infections were established in rabbits using Staphylococcus aureus and treated with G-PNDJ or no hydrogel post-débridement.
• Renal function was monitored in rats receiving subcutaneous G-PNDJ injections at various doses.

Main Results:

• Gentamicin release was sustained for 7 days, comparable to bone cement.
• G-PNDJ hydrogel treatment completely eradicated infection in rabbits (0/8) compared to controls (8/8).
• Transient renal dysfunction was observed in rats receiving the highest G-PNDJ dose (3.0 mL).

Conclusions:

• PNDJ hydrogels effectively deliver gentamicin locally, reducing orthopedic infection treatment failure with low systemic exposure.
• High doses of G-PNDJ can cause transient renal dysfunction, necessitating further safety evaluations.
• Resorbable hydrogels show promise for managing implant-associated infections in one-stage surgeries.