The role of intermolecular interactions with penetratin and its analogue on the enhancement of absorption of nasal therapeutic peptides

We investigated the relationship between intermolecular binding and the ability of novel cell-penetrating peptides (CPPs) to enhance the nasal absorption of therapeutic peptides and proteins. The absorption-enhancing effect of a novel l-penetratin analogue, ‘shuffle (R,K fix) 2’ coadministered with...

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Bibliographic Details
Published in:International journal of pharmaceutics 2010-03, Vol.388 (1), p.209-212
Main Authors: Khafagy, El-Sayed, Morishita, Mariko, Takayama, Kozo
Format: Article
Language:English
Subjects:
Administration, Intranasal
Animals
Biological and medical sciences
Carrier Proteins - chemistry
Cell-penetrating peptide (CPP)
Excipients - chemistry
General pharmacology
Glucagon-Like Peptide 1 - administration & dosage
Glucagon-Like Peptide 1 - pharmacokinetics
Insulin - administration & dosage
Insulin - pharmacokinetics
Intermolecular binding
Male
Medical sciences
Nasal absorption
Penetratin analogues
Peptides
Peptides - administration & dosage
Peptides - pharmacokinetics
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Protein Binding
Rats
Rats, Sprague-Dawley
Surface Plasmon Resonance
Surface plasmon resonance (SPR)
Venoms - administration & dosage
Venoms - pharmacokinetics
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Summary:We investigated the relationship between intermolecular binding and the ability of novel cell-penetrating peptides (CPPs) to enhance the nasal absorption of therapeutic peptides and proteins. The absorption-enhancing effect of a novel l-penetratin analogue, ‘shuffle (R,K fix) 2’ coadministered with different biotherapeutic peptides was evaluated after nasal administration in rats. Shuffle (R,K fix) 2 significantly increased the nasal absorption of insulin, glucagon-like-peptide-1 (GLP-1) and exendin-4, compared with the absorption seen with l-penetratin. Intermolecular binding was analyzed by surface plasmon resonance (SPR)-based binding assay. The binding characteristics implied that the higher the amount of CPP bound, the greater the nasal drug absorption. In addition, the calculated binding ratio between CPP and drug proved a critical aspect in enhancing the absorption of insulin and GLP-1. This difference in the enhancing effect of CPPs on nasal drug absorption is attributed to the degree of binding with the therapeutic macromolecule.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2009.12.060