ABSTRACT
In diabetic ulcers, an increased secretion of human neutrophil elastase (HNE) and bacterial infections play crucial roles in hindering healing. Considering that, the present study proposed the development of multi-action polycaprolactone (PCL)/polyethylene glycol (PEG) electrospun fibers incorporating elastase-targeting peptides, AAPV and WAAPV, via blending. Characterization confirmed WAAPV's efficacy in regulating proteolytic enzymes by inhibiting HNE. The engineered fibers, particularly those containing PEG, exhibited optimal wettability but an accelerated degradation that was mitigated with the peptide's inclusion, thus promoting a sustained peptide release over 24 h. Peptide loading was verified indirectly through thermal stability and hydration capacity studies (hydrophobic bonding between PCL and WAAPV and hydrophilic affinities between PCL/PEG and AAPV) and determined at ≈51.1 µg/cm2 and ≈46.0 µg/cm2 for AAPV and ≈48.5 µg/cm2 and ≈51.3 µg/cm2 for WAAPV, respectively, for PCL and PCL/PEG. Both AAPV and WAAPV effectively inhibited HNE, with PEG potentially enhancing this effect by interacting with the peptides and generating detectable peptide-PEG complexes (≈10% inhibition with PCL + peptide fibers after 6 h of incubation, and ≈20% with PCL/PEG + peptide fibers after 4 h incubation). Peptide-loaded fibers demonstrated antibacterial efficacy against Staphylococcus aureus (up to ≈78% inhibition) and Escherichia coli (up to ≈66% inhibition), with peak effectiveness observed after 4 and 2 h of incubation, respectively. This study provides initial insights into the WAAPV's potential for inhibiting HNE and bacteria activities, showing promise for applications in diabetic ulcer management.