|Cohen, I. Kelman -|
Submitted to: International Journal of Pharmaceutics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 7, 2004
Publication Date: August 28, 2004
Citation: Edwards, J.V., Howley, P.S., Cohen, I. 2004. In Vitro Inhibition of Human Neutrophil Elastase by Oleic Acid Albumin Formulations from Derivatized Cotton Wound Dressings. International Journal of Pharmaceutics. 284:1-12. 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. A protein formulation of albumin and oleic acid when attached to derivatized cotton gauze lowers elastase levels under conditions that mimic chronic wound fluid exudate. The albumin/oleic acid formulation on cotton gauze may be applicable to treatment modalities for chronic wounds. Introduction of an 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: Oleic acid is a selective, non-toxic inhibitor of human neutrophil elastase (HNE) and may be of potential use in neutralizing destructively high levels of HNE that occur when chronic wounds become arrested in the inflammatory stage. 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. Oleic acid formulations of bovine serum albumin (BSA) were bound to derivatized cotton gauze and assessed for their inhibition of HNE. Formulations were assessed for elastase inhibition using a colloidal suspension of the fiber-formulation and elastase as an assay to mimic HNE inhibtion in the wound. Cotton gauzes 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. Optimal inhibition of 6.9 milliunits of HNE was observed with formulations that were approximately 9 ug oleic acid/20 ug BSA. Optimal inhibition was observed with formulation-bound fiber having a 50:1 mole ratio (oleic acid to BSA). Release of the oleic acid/albumin formulation from the fiber was measured using quantitative GC analysis. Albumin was found to accelerate elastase hydrolysis of the substrate within a concentration range of 0.2 - 3.5 ug/uL. 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 improve solubility and promote dose response inhibition of HNE from derivatized cotton fibers under aqueous conditions mimicking the chronic wound. The effect of fiber-bound formulation on reducing activity of HNE in solution may be applicable to treatment modalities for chronic wounds.