(M0930-07-43) Dual-Action Core-Shell Nanofibres: Integrating Rapid Antimicrobial Release and Sustained Insulin Delivery for Diabetic Wound Healing

Purpose: Delayed healing and infection risk are significant complications in diabetic wounds. Topical insulin application can accelerate closure by promoting fibroblast activity and mitigating inflammation, whilst levofloxacin serves as a crucial broad-spectrum antibiotic against common diabetic wound pathogens(Oryan and Alemzadeh, 2017). Co-axial electrospinning permits the fabrication of core-shell nanofibres, offering controlled, differential drug release and protection for sensitive biomolecules (Lian et al., 2024). This study aimed to develop and comprehensively characterise a dual-drug delivery system using co-axial electrospun PCL (shell)/PVA (core) nanofibres, encapsulating levofloxacin for rapid release and insulin for sustained delivery and bioactivity preservation, intended as an advanced dressing for synergistic diabetic wound management.

Methods: Polycaprolactone (PCL) solution (10% w/v) containing levofloxacin (1% w/w relative to PCL) constituted the shell precursor. Polyvinyl alcohol (PVA) solution (10% w/v) containing insulin (0.4% w/w relative to PVA) formed the core precursor. These were processed via a co-axial electrospinning system with a defined shell-to-core flow rate ratio (10:1). Precursor solution viscosities were determined using a rheometer. Fabricated nanofibres were characterised for morphology and diameter using Scanning Electron Microscopy (SEM). Mechanical properties (elastic modulus), surface wettability (water contact angle), and thermal behaviour (Differential Scanning Calorimetry/Thermogravimetric) were assessed. In vitro drug release kinetics were studied by incubating fibre samples within dialysis tubing submerged in phosphate-buffered saline (PBS, pH 7.4) at 37°C. Levofloxacin and insulin concentrations in the release medium were quantified using High-Performance Liquid Chromatography (HPLC) and a Micro BCA protein assay kit, respectively.

Results: Uniform core-shell nanofibre morphology was achieved using the specified polymer concentrations and a 10:1 flow rate ratio. The inclusion of levofloxacin and insulin resulted in a significant reduction in the mean nanofibre diameter, decreasing from 1029.07 ± 207.67 nm (drug-free control) to 480.70 ± 87.30 nm (drug-loaded). This reduction is likely attributed to the influence of the drugs on the electrical conductivity, surface tension, and viscosity of the electrospinning solutions. Water contact angle measurements (133.85 ± 0.18°) confirmed the hydrophobic surface nature of the PCL-based fibres, whilst their high surface area-to-volume ratio intrinsically supports moisture vapour transmission and exudate management. Mechanical testing revealed an elastic modulus of 5.19 ± 1.07 MPa, consistent with values suitable for flexible wound dressing applications. In vitro release studies demonstrated a biphasic profile: rapid release of levofloxacin from the shell within the initial 3 hours, followed by sustained insulin release from the core, achieving approximately 88% cumulative release over a 7-day period. Crucially, the core-shell structure effectively protected the encapsulated insulin, inhibiting significant degradation for at least 7 days under physiological buffer conditions, indicating preservation of its potential bioactivity.

Conclusion: This study successfully demonstrates the fabrication of a multifunctional core-shell nanofibrous dressing via co-axial electrospinning. The platform facilitates rapid release of an antimicrobial agent (levofloxacin) from the shell and sustained delivery of a therapeutic protein (insulin) from the core, whilst effectively preserving insulin's integrity. These characteristics highlight the significant potential of this electrospun system as an advanced, synergistic therapeutic approach for the complex challenges of diabetic wound care.

References: Lian, S., Lamprou, D., Zhao, M., 2024. Electrospinning technologies for the delivery of Biopharmaceuticals: Current status and future trends. Int. J. Pharm. 651, 123641.
Oryan, A., Alemzadeh, E., 2017. Effects of insulin on wound healing: A review of animal and human evidences. Life Sci. 174, 59–67.
Valizadeh, A., Shirzad, M., Pourmand, M.R., Farahmandfar, M., Sereshti, H., Amani, A., 2020. Levofloxacin nanoemulsion gel has a powerful healing effect on infected wound in streptozotocin-induced diabetic rats. Drug Deliv. and Transl. Res. 11, 292–304.

Acknowledgements: This project was supported by Queen’s University Belfast/Chinese Scholarship Council (CSC) Scholarship (CSC NO.202208060396).


SEM Figure for Levofloxacin-insulin-loaded electropsun fibres


Release profile for Levofloxacin-insulin-loaded electropsun fibres