TY - JOUR
T1 - Nebulization of single-chain tissue-type and single-chain urokinase plasminogen activator for treatment of inhalational smoke-induced acute lung injury
AU - Surasarang, Soraya Hengsawas
AU - Sahakijpijarn, Sawittree
AU - Florova, Galina
AU - Komissarov, Andrey A.
AU - Nelson, Christina L.
AU - Perenlei, Enkhbaatar
AU - Fukuda, Satoshi
AU - Wolfson, Marla R.
AU - Shaffer, Thomas H.
AU - Idell, Steven
AU - Williams, Robert O.
N1 - Publisher Copyright:
© 2018
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
KW - Inhalational smoke-induced acute lung injury
KW - Lyophilization
KW - Nebulization
KW - Pulmonary delivery
KW - Single-chain tissue-type plasminogen activator
KW - Single-chain urokinase plasminogen activator
KW - Vibrating mesh nebulizers
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U2 - 10.1016/j.jddst.2018.04.013
DO - 10.1016/j.jddst.2018.04.013
M3 - Article
AN - SCOPUS:85046625686
SN - 1773-2247
VL - 46
SP - 19
EP - 27
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
ER -