(T1430-01-03) Coaxial Electrospun Fabric as a Drug Delivery Platform for Mafenide Acetate and Polyhexanide to Combat Burn Wound-Associated Infection

Purpose: Traditional treatment of infected burn wounds use cream based products such as Sulfamylon (contains mafenide acetate) and Silvadene (contains silver sulfadiazine) in a hospital setting. For medics, a lightweight bandage with a small footprint is more suitable to fit in the aids bag for carry and deployment on the battlefield. Electrospun fabric is an ideal drug delivery platform due to its lightweight consistency, versatility in design, and ability to load drugs of low solubility. The purpose of this study was to formulate mafenide acetate, a drug highly effective against Gram-negative bacteria and polyhexanide (PHMB), a polymeric cationic antimicrobial agent highly effective against Gram-positive bacteria, in coaxial phase electrospun fibers to combat infection in a battlefield setting. Moreover, this study explored the use of coaxial electrospinning to minimize burst release as well as the use of a hydrophilic or hydrophobic core as vehicle for the agents.

Methods: Mafenide acetate was commercially purchased in powder form. PHMB as a 20% w/v solution was lyophilized to produce a powder form. Coaxial electrospun nanofibers (Graphic 1) were fabricated using Fluidnatek® LE-100 with the following configuration: outer shell formulation was 12% w/v polycaprolactone in 90:10 1,1,1,3,3,3-hexafluoro-2-propanol: N,N-Dimethyformamide (HFP:DMF) and the inner core formulation was dependent of the results from the solvent and polymer scouting. The outer shell flow rate was varied (1.8, 2, 2.2, and 2.4 mL/hr) to determine the ideal flow rate that ensured encapsulation of the agents. Fiber morphology was monitored using a benchtop Scanning Electron Microscope (SEM). In vitro release test was performed using a Franz cell system. Drug activity was determined using zone of inhibition test against drug-resistant Pseudomonas aeruginosa and Staphylococcus aureus.

Results: Mafenide acetate and PHMB were both soluble in 70% ethanol, 70% isopropyl alcohol, methanol, and HFP. Based on SEM images, hydrophilic inner core (10% w/v polyethylene 4500) showed inconsistent fiber diameter and petal-like formations whereas the hydrophobic core (4% w/v polycaprolactone) showed consistent fiber diameters. Furthermore, SEM images showed that uniform nanofibers were produced with 12% polycaprolactone outer shell and 4% w/v polycaprolactone inner core (containing both PHMB and mafenide acetate). An outer shell flow rate of at least 2 mL/hr was required to overcome the burst release due to incomplete encapsulation of agents in the inner core based on the release profiles. Compared to the single-phase design, coaxial-phase resulted in extended release of mafenide acetate and PHMB from the electrospun fabrics; the single phase released both drugs within an hour whereas the coaxial phase released the drugs within 8 hours (Graphic 2). For testing antimicrobial activity, combination of mafenide acetate and PHMB yielded a larger zone of inhibition on Pseudomonas aeruginosa and Staphylococcus aureus when compared to their individual effects (Graphic 3). This also confirmed that both drugs in combination retained their activity against pathogenic bacteria.

Conclusion: A hydrophobic core and hydrophobic outer shell produced uniform mafenide acetate-PHMB loaded electrospun fibers. The coaxial-phase design of electrospun fabric resulted in extended release of mafenide acetate and PHMB up to 8 hours. Mafenide acetate and PHMB retained their activity against pathogenic bacteria when loaded in electrospun nanofibers concomitantly.

Acknowledgements: The opinions or assertion contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the U.S. Army Medical Department, Department of the Army, DoD, or the U.S. Government.


Schematic diagram of electrospinning process.


Mafenide acetate and PHMB release comparison between single and coaxial phases of electrospinning.


Zone of inhibition against Pseudomonas aeruginosa (left) and Staphylococcus aureus (right). Clockwise (Silvadene, PHMB only, mafenide acetate only, PHMB + mafenide acetate, Sulfamylon).