Local Antifungal Delivery With Degradable, Modified Chitosan Sponges

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Authors: Parker, AC; Jennings, JA; Courtney, HS; Bumgardner, JD; Haggard, WO.
The University of Memphis, Memphis, TN

Title: Local Antifungal Delivery With Degradable, Modified Chitosan Sponges

Background: Traumatic extremity injuries are very susceptible to multiple pathogenic bacteria and fungi. Fungal infections have become increasingly problematic, with higher amputation rates than those from bacterial infections. Hydrophobic antifungals can also be difficult to incorporate into local drug delivery systems. The incorporation of a biocompatible polymer, used for hydrophobic drug delivery, into the chitosan sponge local delivery system could create an adjunctive therapy for delivering antimicrobials for early abatement of infection.

Hypothesis/Purpose: This preliminary research study analyzes whether the incorporation of a biocompatible polymer into the chitosan sponges allows for Amphotericin B (Amp B) elution and sponge degradation.

Methods: Modified chitosan sponges were made by combining chitosan with a common biocompatible polymer in two different acid solutions. Sponges were frozen, lyophilized, and loaded with 1 mg/ml of Amp B. Elution testing was conducted over 72 hours and antifungal concentrations were measured using UV- Vis spectroscopy. A mass based degradation study of the sponges was conducted in 1 mg/ml of lysozyme solution over 4 days.

Results: Both the unmodified and modified chitosan sponges released Amp B over 72 hours; it appears that the chitosan sponge modification reduced the Amp B burst release seen in the unmodified sponges by 58-89% (Figure 1). All of the initial modified sponge formulations released relatively similar levels of Amp B throughout the elution study. Unmodified sponges only degraded by approximately 1% after 4 days, while most of the modified sponges exhibited degradation from 1-10%. However, a modified sponge made with a different type of acid reached a degradation of 55% after 4 days.

Discussion: These results indicate that the incorporation of the biocompatible polymer into the chitosan sponges results in a degradable local drug delivery system with potential for antifungal delivery. These modified sponges' reduced antifungal burst release should prove beneficial for local tissue response, since antifungals can be locally cytotoxic. In upcoming studies, fungicidal activity testing with clinical isolates will be explored, as well as elution testing with antibiotics and antifungals.

Local Antifungal Delivery With Degradable, Modified Chitosan Sponges