Therapeutic utility of a novel tight junction modulating peptide for enhancing intranasal drug delivery
| Autor: | Michael E. Houston, Ching-Yuan Li, Kristine T. Eiting, Ken Farber, Daniel Morris, Henry R. Costantino, Anthony P. Sileno, Kunyuan Cui, Shu-Chih Chen, Alexis Kays Leonard, Paul H. Johnson, Steven C. Quay |
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| Rok vydání: | 2006 |
| Předmět: |
Calcitonin
medicine.drug_class Chemistry Pharmaceutical Pharmaceutical Science Excipient Biological Availability Peptide Pharmacology In Vitro Techniques Permeability Tight Junctions Drug Delivery Systems Pharmacokinetics Drug Stability In vivo medicine Electric Impedance Animals Peptide YY Administration Intranasal chemistry.chemical_classification Galantamine Epithelial Cells Hydrogen-Ion Concentration Peptide Fragments chemistry Acetylcholinesterase inhibitor Parathyroid Hormone Area Under Curve Nasal administration Rabbits Peptides medicine.drug |
| Zdroj: | Journal of pharmaceutical sciences. 95(6) |
| ISSN: | 0022-3549 |
| Popis: | Previously, a novel tight junction modulating (TJM) peptide was described affording a transient, reversible lowering of transepithelial electrical resistance (TER) in an in vitro model of nasal epithelial tissue. In the current report, this peptide has been further evaluated for utility as an excipient in transepithelial drug formulations. Chemical stability was optimal at neutral to acidic pH when stored at or below room temperature, conditions relevant to therapeutic formulations. The TJM peptide was tested in the in vitro tissue model for potential to enhance permeation of a low-molecular-weight (LMW) drug, namely the acetylcholinesterase inhibitor galantamine, as well as three peptides, salmon calcitonin, parathyroid hormone 1-34 (PTH(1-34)), and peptide YY 3-36 (PYY(3-36)). In all cases, the TJM peptide afforded a dramatic improvement in drug permeation across epithelial tissue. In addition, a formulation containing PYY(3-36) and TJM peptide was dosed intranasally in rabbits, resulting in a dramatic increase in bioavailability. The TJM peptide was as or more effective in enhancing PYY(3-36) permeation in vivo at a 1000-fold lower molar concentration compared to using LMW enhancers. Based on these in vitro and in vivo data, the novel TJM peptide represents a promising advancement in intranasal formulation development. |
| Databáze: | OpenAIRE |
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