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Characterization of local delivery with amphotericin B and vancomycin from modified chitosan sponges and functional
Ashley Cox Parker1, Karen E Beenken, Jessica Amber Jennings
1The University of Memphis, Memphis, Tennessee.
Abstract:
Polymicrobial musculoskeletal wound infections are troublesome complications and can be difficult to treat when caused by invasive fungi or bacteria. However, few local antifungal delivery systems have been studied. Chitosan and polyethylene glycol (PEG) sponge local antifungal delivery systems have been developed for adjunctive therapy to reduce musculoskeletal wound contamination. This study evaluated the effects of blending PEG, at 6,000 or 8,000 g/mol, with chitosan in sponge form on in vitro amphotericin B and vancomycin elution, eluate activity, cytocompatibility, and in vivo prevention of a bacterial biofilm. Blended chitosan sponges released both amphotericin B and vancomycin in vitro. All tested amphotericin B eluates remained active against Candida albicans, and vancomycin eluates from blended sponges maintained activity against Staphylococcus aureus. Amphotericin B eluates obtained after 1 h from blended sponges elicited 62-95% losses in fibroblast viability, but 3 h eluates only caused 22-60% decreases in viability. In a Staphylococcus aureus infected mouse catheter biofilm prevention model, vancomycin loaded chitosan/PEG 6000 sponge cleared bacteria from 100% of the catheters, with reduced clearance rate observed in other sponges. These results indicate that the chitosan/PEG blended sponges have potential for local antifungal and/or antibiotic combination delivery as an adjunctive therapy to prevent wound infections.
Insights
Chitosan/PEG sponges effectively deliver antifungals and antibiotics to combat challenging wound infections. These novel delivery systems show promise in preventing bacterial biofilms and treating polymicrobial infections.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Pharmacology
Background:
- Musculoskeletal wound infections caused by fungi and bacteria are difficult to treat.
- Limited local antifungal delivery systems exist for these infections.
- Chitosan and polyethylene glycol (PEG) sponges are being explored for drug delivery.
Purpose of the Study:
- To evaluate chitosan/PEG blended sponges for local delivery of amphotericin B and vancomycin.
- To assess drug elution, antimicrobial activity, cytocompatibility, and in vivo biofilm prevention.
Main Methods:
- Chitosan sponges were blended with PEG (6,000 or 8,000 g/mol).
- In vitro drug release, antimicrobial activity against Candida albicans and Staphylococcus aureus, and fibroblast viability were tested.
- In vivo efficacy was evaluated using a Staphylococcus aureus catheter biofilm model in mice.
Main Results:
- Blended sponges successfully released both amphotericin B and vancomycin in vitro.
- All eluates demonstrated antimicrobial activity; vancomycin sponges cleared 100% of bacterial biofilms in vivo.
- Short-term amphotericin B eluates showed cytotoxicity to fibroblasts, but viability improved with longer elution times.
Conclusions:
- Chitosan/PEG blended sponges are effective for local delivery of antifungals and antibiotics.
- These sponges show potential as an adjunctive therapy for preventing and treating polymicrobial wound infections.
- Further research into optimizing drug release and minimizing cytotoxicity is warranted.
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