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Antibacterial fibrous drug delivery systems with different drug release profiles for the treatment of wound infections

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Antibacterial fibrous drug delivery systems with different drug release profiles for the treatment of wound infections

 

 Liis Saks1, Andres Meos1, Ivo Laidmäe1, Tavo Romann2, Marta Putrinš3, Tanel Tenson3, Karin Kogermann1,

1Institute of Pharmacy, University of Tartu, Estonia; 2Institute of Chemistry, University of Tartu, Estonia; 3Institute of Technology, University of Tartu, Estonia

 

Introduction

Antibacterial drug-loaded electrospun nano- and microfibrous dressings are of major interest as novel topical drug delivery systems for managing chronic wound infections. Electrospinning (Fig. 1) is a simple and versatile process by which polymer nano- and microfibers can be produced using an electrostatically driven jet of polymer solution or polymer melt. Electrospun fibers have many useful properties for wound care applications, including oxygen permeability, high porosity and surface-to-volume ratio that can promote haemostasis and absorb wound exudates. Morphology of electrospun nanofibers is similar to natural extracellular matrix in the skin that promotes cell adhesion, migration and proliferation [1,2].

Aims

To develop electrospun wound dressings containing antibacterial agent chloramphenicol (CAM) and investigate the effects of carrier polymers on the properties important for the treatment of infected wounds.

Materials and Methods

Model antibacterial drug – Chloramphenicol (CAM)

Carrier polymers – Polycaprolactone (PCL) and polyethylene oxide (PEO)

Electrospinning solutions:

I. PCL 12.5% in chloroform and methanol (3:1 V/V) / + 4% CAM

II. PCL 10%, PEO 2% in chloroform and methanol (3:1 V/V) / + 4% CAM

Characterization of electrospun matrices:

ØScanning Electron Microscopy (SEM)
ØX-ray Powder Diffractometry (XRPD)
ØDifferential Scanning Calorimetry (DSC)
ØDrug-release: Modified dissolution test
ØAntibacterial activity: Diffusion test on agar plates (E. coli MG1655, LB plates)
ØCytotoxicity: CellTiter-Glo® Luminescent Cell Viability Assay (NIH 3T3 cells)

Results and discussion

PCL+CAM fibers were nanofibers with an average diameter of 496 nm (±339 nm) and PCL+PEO+CAM fibers were microfibers - average diameter was 1897 nm (±432) nm (Fig.2).

Absence of characteristic diffraction reflections of CAM in the XRPD patterns of electrospun fibers suggests amorphous state of the drug (Fig. 3). These reflections can be seen with reference samples made by melting the drug and polymer(s) together. The amorphous form of the drug in the fibers was further confirmed with DSC as no CAM melting endotherm was present in drug-loaded matrices.

PCL-PEO-CAM fibers released the drug fast (Fig. 4a), as more than 90% of the drug was released within the first 15 minutes. In contrast, PCL-CAM fibers released about 19% of CAM in the first hour and after 78 hours only 60% of the drug was released (Fig. 4b).

Cell viability assay showed good tolerability of fiber mats by mammalian cells. Disc diffusion method showed that effective antibacterial concentrations were achieved with both fiber mats, seen by the areas of growth inhibition around the drug-loaded matrices (Fig. 5)

Conclusion

Electrospun CAM-loaded biocompatible nano- and microfibrous matrices with suitable antibacterial properties and different drug release profiles applicable for the treatment of infected wounds were developed.

References

1.Charernsriwilaiwat N, Rojanarata T, Ngawhirunpat T, Opanasopit P. Electrospun chitosan/polyvinyl alcohol nanofibre mats for wound healing. Int Wound J 2014; 11:215–222
2.Vasita R, Katti DS. Nanofibers and their applications in tissue engineering. Int. J. Nanomedicine 2006; 1:15–30.

3.Retrieved from: http://faculty.ksu.edu.sa/waheed.almasry/Pages/NanofiberTechnology.aspx

 

 

 

 

 

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