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

作者：Surasarang Soraya Hengsawas; Sahakijpijarn Sawittree; Florova Galina; Komissarov Andrey A; Nelson Christina L; Perenlei Enkhbaatar; Fukuda Satoshi; Wolfson Marla R; Shaffer Thomas H; Idell Steven; Williams Robert O III^*

来源：JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2018, 46: 19-27.

DOI：10.1016/j.jddst.2018.04.013

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

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 (R) Pro (active) and EZ Breathe (R) (passive)). Both the Aeroneb (R) Pro and EZ Breathe (R) vibrating mesh nebulizers produced atomized droplets of protein solution of similar size of less than about 5 mu m, 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.

• 出版日期2018-8