Fabrication of pomegranate peel extract/honey nanofibers loaded with bee venom as effective antibacterial wound dressings

Abstract

In spite of the emerging advances in the field of wound dressings, there is still a deep need for the development of novel natural based dressings to offer a safe alternative for traditional wound dressings and most importantly fight against antibacterial resistance. The aim of this study is to develop novel honey based nanofibrous wound dressing for achieving both effective and safe treatment and investigate the dressings for antibacterial activity, cytotoxicity and in vivo wound healing effect in a rat wound model. Natural products; Honey, Pomegranate peel extract (PPP), and bee venom (BV), known for their antibacterial and anti-inflammatory properties, were used in combination with Polyvinyl alcohol (PVA), to develop a novel natural-based nanofibrous wound dressing. Methanolic pomegranate peel extract was prepared and mixed with either Manuka honey (MH) or lyophilized multiflora honey powder (LH). By testing electrospun samples: (10% MH/ 1% PPP), (20% MH/ 2% PPP) and (25%/ 2.5%PPP) against S. aureus, it was shown that antibacterial activity increases with increasing the MH/PPP concentration. BV was added to the honey/PPP combination to prepare (25 % MH/2.5 % PPP/ 0.01%BV) and (25 % LH/2.5 % PPP/0.01% BV) nanofibers. Scanning electron microscopy (SEM) showed that all samples had good morphology with no beads. Samples showed moderate swelling capacity in comparison to PVA while all samples showed better water loss capacity than PVA. Antibacterial tests showed significant antibacterial activity against both strains tested compared to both controls used (P< 0.0001). Against S. aureus, samples containing BV were slightly more effective than the sample without BV (P < 0.05). Against E. coli, sample (MH/PPP/BV) was slightly more effective than sample (LH/PPP/BV) (P < 0.05). In the cytotoxicity assay, all samples showed 100 - 120 % viability which indicated that the produced dressings have no significant cytotoxic effects. Results of the in vivo wound healing assay showed that treatment groups (25% MH/2.5%PPP), (25% MH/2.5%PPP/ 0.01 %BV), and (25% LH/2.5 %PPP/ 0.01% BV) had a significantly decreased wound surface areas compared to both controls at days 3 and day 5 (P <0.0001). All treatment groups reached complete healing by day 10 compared to day 14 in the case of both controls. On the histological side, PVA control group showed poor healing compared to all treatment groups. MH/PPP/BV sample micrographs showed excellent healing at day 10 resembling intact skin as shown by histological assessment. These results indicate that MH/PPP/BV combination can be considered as a promising formula to promote wound healing. However, further analysis is required to confirm the results and address the potential of the combination on more challenging wounds.