|Edwards, Judson - Vince|
|Cohen, I. kelman|
Submitted to: International Journal of Pharmaceutics
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/14/2007
Publication Date: 4/1/2007
Citation: Edwards, J.V., Howley, P.S., Cohen, I., Davis, R., Mintzer, E., Mashchak, A., Goheen, S.C. 2007. Oleic Acid Transfer from Cotton by Albumin Binding as a Potential Cationic Protease-Lowering Effect for Chronic Wound Dressings. International Journal of Pharmaceutics. 340:42-51. 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 enzymes are human neutrophil elastase and cathepsin G. High levels of these proteases 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: High elastase and cathepsin G activities have been observed in chronic wounds. These levels can inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid (18:1) is a non-toxic elastase inhibitor with some potential for redressing the imbalance of elastase activity found in chronic wounds. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of 18:1 by albumin under conditions mimicking chronic wounds. 18:1-treated cotton was examined for its ability to bind and release the fatty acid in the presence of albumin. The mechanism of 18:1 uptake from cotton and binding on albumin was examined with both intact dressings and cotton-fiber designed chromatography. Raman spectra of the albumin-18:1 complexes under liquid-liquid equilibrium conditions revealed fully saturated albumin-18:1 complexes with a 1:1 weight ratio of albumin:18:1. Cotton chromatography under liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of 18:1 per hole albumin. Cotton was contrasted with hydrogel, and hydrocolloid wound dressings for its comparative ability to lower elastase activity. Each dressing material evaluated was found to release 18:1 in the presence of albumin with significant inhibition of elastase activity. The 18:1-formulated wound dressings lowered elastase activity in a dose dependent manner in the order cotton gauze > hydrogel > hydrocolloid. In contrast, the cationic serine protease Cathepsin G was inhibited by 18:1 within a narrow range of 18:1-cotton formulations. Four percent Albumin solutions was most effective in binding cotton bound-18:1. However, 2% albumin was sufficient to transfer quantities of 18:1 necessary to achieve a significant elastase-lowering effect. Formulations with 128 mg 18:1/g cotton gauze had equivalent elastase lowering with 1-4% albumin. 18:1 bound to cotton wound dressings may have promise in the selective lowering of cationic serine protease activity useful in topical application for chronic inflammatory pathogenesis.