|Cohen, I. Kelman - VIRGINIA COMMONWEALTH UNV|
Submitted to: Journal of Wound Repair and Regeneration
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 2, 2002
Publication Date: November 5, 2002
Citation: Edwards, J.V., Howley, P.S., Cohen, I. 2002. Albumin Displacement of Oleic Acid from Wound Dressings Promotes an Elastase-Lowering Effect in Chronic Wound Fluid [abstract]. Journal of Wound Repair and Regeneration. 13(2):A36. Interpretive Summary: Chronic wounds are a major worldwide health problem. This research is directed at strengthening the role of cotton-based textiles in the growing market of high tech wound dressings. This work demonstrates an important technology for development of value-added cotton-based wound dressings. An improvement on cotton gauze to accelerate healing in patients with bedsores and ulcers is the ultimate goal of this work. Cotton gauze can be modified to reduce the activity of a destructive enzyme found to keep chronic wounds from healing. The destructive enzyme is human neutrophil elastase. High levels of elastase in the non-healing wound break down the recruitment of new tissue necessary for healing to take place. Oleic acid placed on cotton gauze inhibits elastase by acting in sync with wound proteins that displace oleic acid from the cotton fiber and promote elastase inhibition. Introduction of this type of elastase inhibitor-based, cotton dressing for treatment of chronic wounds would boost cotton's share of the rapidly growing high tech wound care market, and aid both the consumer and the cotton farmer by providing an economic value-added product.
Technical Abstract: Human neutrophil elastase (HNE) is elevated in chronic wounds. Oleic acid albumin formulatons that inhibit HNE may be applicable to treatment modalities for chronic wounds. Oleic acid /albumin formulations with mole ratios of 100:1, 50:1, and 25:1 (oleic acid to albumin) were prepared and found to have dose response inhibition properties against HNE. The IC50 values for inhibition of HNE with oleic acid/ albumin formulations were 0.029 - 0.049 mM.. Oleic acid/ albumin (BSA) formulations were bound to positively and negatively charged cotton wound dressings and assessed for elastase inhibition using a colloidal suspension of the fiber-formulation as an assay to mimic HNE inhibition in the wound. Cotton derivatized with both carboxylate and amine functional groups were combined with oleic acid/albumin formulations at a maximum loading of 0.030 mg oleic acid + 0.14 mg BSA/mg fiber. The IC50 values for inhibition of HNE with oleic acid/albumin formulations bound to derivatized cotton were 0.26 - 0.42 mM. Release of the oleic acid/albumin formulation from the fiber was measured using quantitative GC analysis. Approximately thirty-five to fifty per cent of the fiber bound formulation was released into solution within the first fifteen minutes of incubation. Albumin was found to enhance the rate of elastase hydrolysis of the substrate within a concentration range of 0.3 - 50g/L. The acceleration of HNE substrate hydrolysis by albumin required increased concentration of inhibitor in the formulation to obtain complete inhibition of HNE. Oleic acid formulations prepared with albumin enable transport, solubility and promote dose response inhibition of HNE from derivatized cotton fibers under aqueous conditions mimicking the chronic wound.