Abstract
The use of combination therapies for the treatment of a range of conditions is now well established, with the component drugs usually being delivered either as distinct medicaments or combination products that contain physical mixes of the two active ingredients. There is, however, a compelling argument for the development of compartmentalised systems whereby the release, stability and incorporation environment of the different drugs may be tailored. Here we outline the development of polymeric fine fiber systems whereby two drugs used for the treatment of wounds may be separately incorporated. Fibers were delivered using a newly developed handheld electrospinning device that allows treatment at the site of need. Crucially, the delivery system is portable and may be used for the administration of drug-loaded fibers directly into the wound in situ, thereby potentially allowing domiciliary or site-of-trauma administration. The three-layered fiber developed in this study has polyethylene glycol as the outermost layer, serving as a structural support for the inner layers. The inner layers comprised iodine complexed with polyvinylpyrrolidone (PVP) and metronidazole dispersed in polycaprolactone (PCL) as a slow release core. The systems were characterized in terms of structure and architecture using scanning electron microscopy, transmission electron microscopy, attenuated total reflection Fourier transform infrared spectroscopy and diffractometry. As antibacterial creams are still used for managing infected wounds, the performance of our trilayered fiber was studied in comparison with creams containing similar active drugs. Drug release was measured by UV analysis, while antimicrobial efficiency was measured using agar diffusion and suspension methods. It was found that the trilayered systems, averaging 3.16 µm in diameter, released more drug over the study period and were confirmed by the microbacterial studies to be more effective against P. aeruginosa, a bacterium commonly implicated in infected wounds. Overall, the portable system has been shown to be capable of not only incorporating the two drugs in distinct layers but also of delivering adequate amounts of drugs for a more effective antibacterial activity. The portability of the device and its ability to generate distinct layers of multiple active ingredients make it promising for further development for wound healing applications in terms of both practical applicability and antimicrobial efficacy.
Highlights
Chronic wounds remain a significant burden on the patient population and healthcare systems worldwide [1], with infection being the likeliest cause of delay in healing
As a proof-of-concept to explore the use of a trilayered fibrous system, we develop a new, improved combination therapy consisting of iodine and metronidazole (MTZ) for wound dressing applications
The apparatus is easy to operate and can be hand-held for the direct generation of structures at the point-of-use (Figure 1). We demonstrated how this miniaturised device could be used in the manufacture of a system containing silver nanoparticles as antibacterial agents to be applied as a wound dressing [17]
Summary
Chronic wounds remain a significant burden on the patient population and healthcare systems worldwide [1], with infection being the likeliest cause of delay in healing. The formation of biofilms from the secretions of infecting bacteria, into which they become embedded, further inhibits healing. One treatment approach is the application of antiseptics and antibiotics, preferably in combination, in order to simultaneously suppress biofilm formation [3] and prevent infection [4]. There is a need for wound management strategies that utilise a multifaceted approach to simultaneously target pathogeneses of the wound. As it is common to isolate several microbial species from infected wounds such as DFUs [7], an approach utilising combination therapies where multiple active agents are efficiently delivered simultaneously will be required for treating such wounds
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