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On employing a translationally controlled tumor protein-derived protein transduction domain analog for transmucosal delivery of drugs

Title
On employing a translationally controlled tumor protein-derived protein transduction domain analog for transmucosal delivery of drugs
Authors
Bae H.-D.Lee K.
Ewha Authors
이경림배해득
SCOPUS Author ID
이경림scopus; 배해득scopus
Issue Date
2013
Journal Title
Journal of Controlled Release
ISSN
0168-3659JCR Link
Citation
vol. 170, no. 3, pp. 358 - 364
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Protein transduction domains (PTDs) are recognized as promising vehicles for the delivery of macromolecular drugs. We have previously shown that a region in the N-terminus (residues 1-10) of translationally controlled tumor protein (TCTP) contains a PTD (TCTP-PTD), MIIYRDLISH, which can serve as a vehicle for the delivery of macromolecules into the cells and tissues. In the current study, we evaluated the potential and safety of TCTP-PTD and its three mutant analogs as nasal absorption enhancers for delivery of drugs. We conducted this evaluation employing insulinastest drug. We examined the degreeto which insulin was absorbedin nasal mucosa and also if any mucosal damage occurs following such nasal delivery of insulin using TCTP-PTDs as a vehicle. The systemic delivery of insulin was assessed by measuring the changes in blood glucose levels after nasal coadministration insulin and four PTDs. Of the three TCTP-PTD analogs examined, one, TCTP-PTD analog (MIIFRALISHKK) significantly enhanced the nasal absorption of insulin in both normal and streptozotocin-induced diabetic mice. The relative pharmacological bioavailability of insulin nasally coadministered with the TCTP-PTD analog was 21.3% relative to the subcutaneous route. Molecular association between insulin and the TCTP-PTD analog was observed by fluorescence resonance energy transfer measurements. The binding between the TCTP-PTD analog and insulin may enable the penetration of insulin through the nasal mucosa. Histological examination of mice nasal mucosa 7 days after repeated nasal administration showed no evidence of toxicity at the site of nasal administration. In this study using insulin as a test system we demonstrate that the TCTP-PTD analog offers a promising approach for nasal peptides and protein-drugs delivery. © 2013 Elsevier B.V. All rights reserved.
DOI
10.1016/j.jconrel.2013.06.010
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약학대학 > 약학과 > Journal papers
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