A high-affinity peptide for nicotinic acetylcholine receptor-alpha 1 and its potential use in pulmonary drug delivery

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In pulmonary drug delivery, the ability of an affinity molecule to bind to lung epithelium may prolong retention of therapeutic molecules within the lung and consequently yield higher overall bioavailability. To this end, we screened a library of structurally constrained peptides ('aptides') using phage-display technology and identified a high-affinity aptide for the mouse nicotinic acetylcholine receptor-alpha 1 (nAChR-alpha 1). The isolated aptide (APT(nAChR-alpha 1)) bound to its target protein with high affinity (K-d = 47 nM). Alexa 488-labeled APT(nAChR-alpha 1) showed preferential binding to nAChR-alpha 1-positive mouse lung epithelial cells and mouse muscle cells. Furthermore, the aptide exhibited substantial binding in nAChR-a1-positive tissue sections of muscle, trachea and lung, but not in liver, kidney or spleen tissues, which are nAChR-alpha 1-negative. In an in vivo experiment, a high-intensity fluorescence signal was observed in the entire lung up to 50 h after tracheal injection of Cy5.5-APTnAChR-alpha 1, whereas most of the fluorescence signal from a Cy5.5-labeled scrambled peptide washed out within 20 h after injection. Taken together, these results indicate that the high-affinity peptide for nAChR-alpha 1 identified here bound tightly to lung epithelium and thus exhibited a long residence time in this tissue, suggesting that the peptide could be used for pulmonary delivery of active pharmaceuticals.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2014-10
Language
English
Article Type
Article
Keywords

MEDIATED TRANSCYTOSIS; CYSTIC-FIBROSIS; INHALATION; INSULIN; FIBRONECTIN; ABSORPTION; EXPRESSION; DEPOSITION; PROTEINS; HUMANS

Citation

JOURNAL OF CONTROLLED RELEASE, v.192, pp.141 - 147

ISSN
0168-3659
DOI
10.1016/j.jconrel.2014.07.006
URI
http://hdl.handle.net/10203/192931
Appears in Collection
BS-Journal Papers(저널논문)
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