Nebulization of single-chain tissue-type and single-chain urokinase plasminogen activator for treatment of inhalational smoke-induced acute lung injury

Soraya Hengsawas Surasarang, Sawittree Sahakijpijarn, Galina Florova, Andrey A. Komissarov, Christina L. Nelson, Enkhbaatar Perenlei, Satoshi Fukuda, Marla R. Wolfson, Thomas H. Shaffer, Steven Idell, Robert O. Williams

Research output: Contribution to journalArticle

Abstract

Single-chain tissue-type plasminogen activator (sctPA) and single-chain urokinase plasminogen activator (scuPA) have attracted interest as enzymes for the treatment of inhalational smoke-induced acute lung injury (ISALI). In this study, the pulmonary delivery of commercial human sctPA and lyophilized scuPA and their reconstituted solution forms were demonstrated using vibrating mesh nebulizers (Aeroneb® Pro (active) and EZ Breathe® (passive)). Both the Aeroneb® Pro and EZ Breathe® vibrating mesh nebulizers produced atomized droplets of protein solution of similar size of less than about 5 μm, which is appropriate for pulmonary delivery. Enzymatic activities of scuPA and of sctPA were determined after nebulization and both remained stable (88.0% and 93.9%). Additionally, the enzymatic activities of sctPA and tcuPA were not significantly affected by excipients, lyophilization or reconstitution conditions. The results of these studies support further development of inhaled formulations of fibrinolysins for delivery to the lungs following smoke-induced acute pulmonary injury.

Original languageEnglish (US)
Pages (from-to)19-27
Number of pages9
JournalJournal of Drug Delivery Science and Technology
Volume46
DOIs
StatePublished - Aug 2018

Keywords

  • Inhalational smoke-induced acute lung injury
  • Lyophilization
  • Nebulization
  • Pulmonary delivery
  • Single-chain tissue-type plasminogen activator
  • Single-chain urokinase plasminogen activator
  • Vibrating mesh nebulizers

ASJC Scopus subject areas

  • Pharmaceutical Science

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  • Cite this

    Surasarang, S. H., Sahakijpijarn, S., Florova, G., Komissarov, A. A., Nelson, C. L., Perenlei, E., Fukuda, S., Wolfson, M. R., Shaffer, T. H., Idell, S., & Williams, R. O. (2018). Nebulization of single-chain tissue-type and single-chain urokinase plasminogen activator for treatment of inhalational smoke-induced acute lung injury. Journal of Drug Delivery Science and Technology, 46, 19-27. https://doi.org/10.1016/j.jddst.2018.04.013