Increasing prevalence of infected and chronic wounds demands improved therapy options. In this work an electrospun nanofiber dressing with liposomes is suggested, focusing on the dressing’s ability to support tissue regeneration and infection control. Chloramphenicol (CAM) was the chosen antibiotic, added to the nanofibers after first embedded in liposomes to maintain a sustained drug release. Nanofibers spun from five different polymer blends were tested, where pectin and polyethylene oxide (PEO) was identified as the most promising polymer blend, showing superior fiber formation and tensile strength. The wire-electrospinning setup (WES) was selected for its pilot-scale features, and water was applied as the only solvent for green electrospinning and to allow direct liposome incorporation. CAM-liposomes were added to Pectin-PEO nanofibers in the next step. Confocal imaging of rhodamine-labelled liposomes indicated intact liposomes in the fibers after electrospinning. This was supported by the observed in vitroCAM-release, showing that Pectin-PEO-nanofibers with CAM-liposomes had a delayed drug release compared to controls. Biological testing confirmed the antimicrobial efficacy of CAM and good biocompatibility of all CAM-nanofibers. The successful fiber formation and green production process with WES gives a promising outlook for industrial upscaling.
An active wound dressing should address the main goals in wound treatment, which are improved wound healing and reduced infection rates. We developed novel multifunctional nanofibrous wound dressings with three active ingredients: chloramphenicol (CAM), beta-glucan (βG) and chitosan (CHI), of which βG and CHI are active nanofiber-forming biopolymers isolated from the cell walls of Saccharomyces cerevisiae and from shrimp shells, respectively. To evaluate the effect of each active ingredient on the nanofibers’ morphological features and bioactivity, nanofibers with both βG and CHI, only βG, only CHI and only copolymers, polyethylene oxide (PEO) and hydroxypropylmethylcellulose (HPMC) were fabricated. All four nanofiber formulations were also prepared with 1% CAM. The needle-free NanospiderTM technique allowed for the successful production of defect-free nanofibers containing all three active ingredients. The CAM-containing nanofibers had a burst CAM-release and a high absorption capacity. Nanofibers with all active ingredients (βG, CHI and CAM) showed a concentration-dependent anti-inflammatory activity, while maintaining the antimicrobial activity of CAM. The promising anti-inflammatory properties, together with the high absorption capacity and antimicrobial effect, make these multifunctional nanofibers promising as dressings in local treatment of infected and exuding wounds, such as burn wounds.
To relieve the severe economic and social burdens and patient suffering caused by the increasing incidence of chronic wounds, more effective treatments are urgently needed. In this study, we focused on developing a novel sprayable wound dressing with the active ingredient β-1,3/1,6-glucan (βG). Since βG is already available as the active ingredient in a commercial wound healing product provided as a hydrogel in a tube (βG-Gel), the sprayable format should bring clinical benefit by being easily sprayed onto wounds; whilst retaining βG-Gel's physical stability, biological safety and wound healing efficacy. Potentially sprayable βG hydrogels were therefore formulated, based on an experimental design setup. One spray formulation, named βG-Spray, was selected for further investigation, as it showed favorable rheological and spraying properties. The βG-Spray was furthermore found to be stable at room temperature for more than a year, retaining its rheological properties and sprayability. The cytotoxicity of βG-Spray in keratinocytes in vitro, was shown to be promising even at the highest tested concentration of 100 μg/ml. The βG-Spray also displayed favorable fluid affinity characteristics, with a capacity to both donate and absorb close to 10% fluid relative to its own weight. Finally, the βG-Spray was proven comparably effective to the commercial product, βG-Gel, and superior to both the water and the carrier controls (NoβG-Spray), in terms of its ability to promote wound healing in healing-impaired animals. Contraction was found to be the main wound closure mechanism responsible for the improvement seen in the βG-treatment groups (βG-Spray and βG-Gel). In conclusion, the novel sprayable βG formulation, confirmed its potential to expand the clinical use of βG as wound dressing.
The increased prevalence of chronic wounds requires novel treatment options. The aim of this study was to develop a beta-glucan (βG)-loaded nanofiber wound dressing. Nanofibers were prepared using the needle-free Nanospider™ technology, an electrospinning method which enables the production of nanofibers at an industrial scale. The βG was selected as active ingredient based on its confirmed wound healing potential in both animals and humans. Hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) were included as copolymers. Rheological profiles of spinning solutions containing HPMC, PEO, βG, ethanol and water, were optimized. The nanofiber formation was confirmed by Field Emission Scanning Electron Microscopy (FE-SEM), and both nanofibers with (βG-nanofibers) or without βG (NoβG-nanofibers) were evaluated by their swelling index and FT-IR spectroscopy. The formulations, active ingredient and excipients were tested for their possible in vitro toxicity in keratinocytes. Finally, the wound healing potential of the nanofibers was tested in externally induced excisional wounds in male diabetic db/db mice. Three different doses of βG-nanofibers and the βG-free, NoβG-nanofibers, were evaluated for their in vivo wound healing efficacy. All nanofiber-treatments provided improved wound healing as compared to the negative control (water). All βG-nanofiber treated groups exhibited significantly improved wound healing as compared to the NoβG-nanofiber treated group, indicating the potential of βG-nanofibers as wound dressing.
Chronic wounds represent a significant health problem worldwide. There is a need for advanced- and cost-efficient wound healing products able to increase patient comfort and reduce the healing time. The aim of this study was to develop a sprayable hydrogel dressing with beta-glucan (βG) as the active ingredient, targeting future application in the treatment of both chronic and burn wounds. The βG was chosen as an active ingredient because of its promising wound healing capabilities, whereas Carbopol 971P NF (Carbopol) was chosen as the thickening agent in the formulation due to several attractive characteristics such as its low viscosity, low toxicity, high transparency and good ion tolerance. Four different hydrogel formulations were prepared with varying Carbopol concentrations. The higher Carbopol concentration, 0.5% (w/w), was used to prepare three formulations comprising the HighCP:NoβG, HighCP:LowβG and the HighCP:MediumβG formulation, respectively. Lower Carbopol concentration, 0.25% (w/w), was used to prepare the LowCP:HighβG formulation. The content of βG varied from 0.25% in the HighCP:LowβG, 0.5% in the HighCP:MediumβG and 1.0% (w/w) in the LowCP:HighβG formulation, respectively. The first part of the study focused on the rheological characterization of the hydrogels and the fluid affinity testing. All formulations were confirmed to be stable gels; the βG was shown to augment the gel strength by increasing the yield strength of the gel in a dose dependent manner. The stability of the formulations containing either Carbopol alone or in a combination with βG did not deteriorate over 26weeks, and the fluid donation and absorption study indicated a fluid donation profile, which favors healing of dry wounds. The in vivo efficacy of the formulations, evaluated in the modified diabetic male mice (db/db mice), showed that Carbopol alone was unable to induce improved healing and caused adverse reactions in some wounds. The inclusion of βG increased the epithelialization and wound contraction in the db/db mice when given at high βG:Carbopol ratio. The positive effect of βG was, however, not sufficient to counteract the adverse effect of Carbopol, thus a more suitable thickening agent should be investigated for further development of a sprayable wound care product.
BACKGROUND:Beta-glucan pretreatment has been shown to attenuate inflammatory response and to protect against ischemia-reperfusion injury in animal studies. The aims of the present study were to examine the safety of pretreatment with beta-1,3/1,6-glucan in patients scheduled for coronary artery bypass grafting (CABG), and to investigate whether beta-1,3/1,6-glucan pretreatment could suppress inflammatory response and protect against ischemia-reperfusion injury following CABG.METHODS:Twenty one patients scheduled for CABG were assigned to oral beta-1,3/1,6-glucan 700 mg (Group 1) or 1 400 mg (Group 2) five consecutive days before surgery and were compared with a control group (Group 3). Blood samples were drawn preoperatively and on the first, third and fifth postoperative day for analysis of acute-phase reactants, hematology, cytokines and myocardial enzymes.RESULTS:The study drug was well tolerated. Creatine kinase isoenzyme MB was significantly lower in Group 2 compared with controls on the first postoperative day (p = 0.028). Mean change in cardiac troponin T was lower in Group 2 compared with controls (p = 0.028).CONCLUSIONS:Beta-1,3/1,6-glucan pretreatment is safe in patients undergoing CABG and may protect against ischemia reperfusion injury following CABG.
responsivity to TNF-alpha. A series of experiments showed that alterations in the glucose concentrations of the growth medium (5,5 13,5 mM), did not change the cellular content of neither VCAM-1 nor E-selectin, before and after TNF-alpha treatment. Conclusions: We have shown that sera from diabetic patients contain components, capable of inducing VCAM-1 expression in endothelial cells independent of hyperglycemia. Augmented induction of endothelial VCAM-1 expression by circulating factors may play a role in the development of atherosclerosis in diabetes.