Penetratin-Mediated Transepithelial Insulin Permeation: Importance of Cationic Residues and pH for Complexation and Permeation
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Penetratin-Mediated Transepithelial Insulin Permeation: Importance of Cationic Residues and pH for Complexation and Permeation. / Kristensen, Mie; Franzyk, Henrik; Klausen, M. T. ; Iversen, A; Bahnsen, Jesper Søborg; Skyggebjerg, R. B.; Foderà, Vito; Nielsen, Hanne Mørck.
In: A A P S Journal, Vol. 17, No. 5, 2015, p. 1200-1209.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Penetratin-Mediated Transepithelial Insulin Permeation: Importance of Cationic Residues and pH for Complexation and Permeation
AU - Kristensen, Mie
AU - Franzyk, Henrik
AU - Klausen, M. T.
AU - Iversen, A
AU - Bahnsen, Jesper Søborg
AU - Skyggebjerg, R. B.
AU - Foderà, Vito
AU - Nielsen, Hanne Mørck
PY - 2015
Y1 - 2015
N2 - Penetratin is a widely used carrier peptide showing promising potential for mucosal delivery of therapeutic proteins. In the present study, the importance of specific penetratin residues and pH was investigated with respect to complexation with insulin and subsequent transepithelial insulin permeation. Besides penetratin, three analogues were studied. The carrier peptide-insulin complexes were characterized in terms of size and morphology at pH 5, 6.5, and 7.4 by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. At pH 7.4 mainly very large complexes were present, while much smaller complexes dominated at pH 5. Presence of arginine residues in the carrier peptide proved to be a prerequisite for complexation with insulin as well as for enhanced transepithelial insulin permeation in vitro. Rearrangement of tryptophan residues resulted in significantly increased insulin permeation as compared to that of the parent penetratin. In general, pre-complexation with penetratin and its analogues at pH 5 gave rise to increased insulin permeation as compared to that observed at pH 7.4; this finding was further supported by a preliminary in vivo study using the parent penetratin.
AB - Penetratin is a widely used carrier peptide showing promising potential for mucosal delivery of therapeutic proteins. In the present study, the importance of specific penetratin residues and pH was investigated with respect to complexation with insulin and subsequent transepithelial insulin permeation. Besides penetratin, three analogues were studied. The carrier peptide-insulin complexes were characterized in terms of size and morphology at pH 5, 6.5, and 7.4 by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. At pH 7.4 mainly very large complexes were present, while much smaller complexes dominated at pH 5. Presence of arginine residues in the carrier peptide proved to be a prerequisite for complexation with insulin as well as for enhanced transepithelial insulin permeation in vitro. Rearrangement of tryptophan residues resulted in significantly increased insulin permeation as compared to that of the parent penetratin. In general, pre-complexation with penetratin and its analogues at pH 5 gave rise to increased insulin permeation as compared to that observed at pH 7.4; this finding was further supported by a preliminary in vivo study using the parent penetratin.
U2 - 10.1208/s12248-015-9747-3
DO - 10.1208/s12248-015-9747-3
M3 - Journal article
C2 - 25990963
VL - 17
SP - 1200
EP - 1209
JO - A A P S Journal
JF - A A P S Journal
SN - 1550-7416
IS - 5
ER -
ID: 132263725