Development of a Novel Alginate-Based Pleural Sealant

A variety of lung diseases such as emphysema, infections, and lung cancers as well as lung injury from trauma, including battlefield trauma, and complications of respirator life support of critically ill patients in intensive care units can result in lung collapse that can be immediately life-threatening or result in chronic leaking of air or fluid out of the lung. These remain challenging medical problems for which few good options are currently available and result in significant morbidity, mortality, hospital stays, health care costs, and other complications. New options are thus desperately needed. We are developing a novel approach to provide an easy-to-apply lung sealant which can repair lung leaks. This initially involved use of a chemically modified form of alginate, a naturally occurring seaweed derivative, increasingly being explored for a variety of biomedical applications. Particular attributes include easy availability, low cost, easy use, biodegradability, and lack of significant toxicity. In the studies to date, we have done extensive materials characterization not just of modified alginates but now a number of other biologic compounds that also have potential as pleural sealants. We have further extensively evaluated promising compounds using small rodent and large pig ex vivo lung models and have performed initial in vivo evaluations of several compounds in a non-survival surgery rat lung injury model. The studies to date have thus identified several promising compounds that will be further evaluated in the non-survival surgery and also a survival surgery rat lung injury model during the 6 month extension period of the grant. These will lead to a firm platform for further investigations in large animal survival surgery models and subsequent discussions with the FDA about new IND for a clinical investigation.