Antifungal and antibacterial electrospun wound dressings for complex wounds

Mhlanga, Miriam and Serrano, Dolores and Morcom, Tiffany and Couburn, Thais and Lewis, Anthony and Lalatsa, Aikaterina (2019) Antifungal and antibacterial electrospun wound dressings for complex wounds. In: Controlled Released Society 2019 Annual Meeting, 2019-07-21 - 2019-07-24, Palacio de Congresos de Valencia.

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Abstract

Introduction: Management of open fractures wounds, diabetic ulcers and military wounds frequently involve infections with gram-positive or gram-negative bacteria and in some cases invasive fungal infections which are linked to mycotic emboli and delays in reconstructive efforts or amputations. Topical antibiotics and antifungals are recommended and local delivery of antimicrobials through beads or bead pouches along with a water impermeable dressing has been shown to be beneficial 1 . Here we present a dressing prepared by alternating electrospun polymeric mats loaded with combination of antifungal (amphotericin B, AmB) and antibacterial (vancomycin) agents in clinically relevant concentrations that can be used for the treatment of complex wounds. Methods: Electrospun membranes were produced using a Spraybase 30kV electrospinning kit attached to a syringe pump (NE-1000). The collection distance was set to 12 cm and a voltage of 16.5 kV was utilised. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus) (8g) was dissolved in acidified methanol and AmB or vancomycin were dispersed prior to the addition of dichloromethane to elicit a suspension that was perfused at 8mL/h via the inner needle of a co-axial electrospinning needle (~900 µm, Rame-hart Instrument Co). Membranes were collected on foil after a stable “cone-jet” mode and a uniform fiber production process was achieved and stored under desiccated conditions in the fridge till further use. Release experiments were conducted in phosphate buffer (50mM, pH 7.4) and levels were quantified using a validated HPLC method 2 . Membranes were analysed using FT-IR, DSC and TGA and their morphology using SEM 3 . Disk diffusion inhibition halo assays against Candida albicans (strain) were performed as previously described 3 . Results: Amphotericin B membranes contained near 100% of AmB sprayed (1.05±0.96 mg/g) and demonstrated a fibrous morphology with higher curvature than Soluplus electrospun fibers (Figure 1). AmB electrospun dressings were amorphous and FT-IR indicated hydrogen bonding between the protonated amine of Amphotericin B and carbonyl groups of Soluplus. Near 30% release was achieved after 1 hour, while a controlled release profile was observed for the first 2 days. Released AmB was present in monomeric form (UV). Inhibition halo of AmB dressings or AmB DMSO impregnated filter papers (6mm, 10 µg) resulted in comparable halos against C. albicans (23 ± 1 mm and 24 ± 1mm respectively). Currently work is undertaken to characterise vancomycin dressings and combined dressings. Conclusions/Implications: Prepared dressings can be utilised for treatment of complex fungal infected wounds to avoid mycotic embolism.

CORE (COnnecting REpositories)