The prevention of elastase-induced emphysema in hamsters by the intratracheal administration of a synthetic elastase inhibitor bound to albumin microspheres.

Abstract

The peptide, succinyl-alanyl-alanyl-prolyl-valine chloromethylketone (SPCK), a synthetic inhibitor of elastase, was covalently attached to human albumin microspheres (HAM) and administered intratracheally to hamsters 15 min and 8 h prior to the instillation of porcine pancreatic elastase. Pressure-volume relationships and histologic examination of excised lungs after 4 wk showed complete protection from emphysema when SPCK-HAM was administered either 15 min or 8 h before elastase exposure. Concurrent experiments with free SPCK showed that protection was achieved only if elastase was administered within 15 min after the instillation of SPCK. Extending this period to 8 h not only led to a failure of free SPCK to prevent emphysema but actually resulted in more extensive air-space enlargement. The prolonged effectiveness conferred by the attachment of SPCK to a biodegradable carrier should reduce the frequency with which it would have to be administered for the therapeutic intervention of emphysema and should minimize any toxic side reactions.