Therapeutic utility of a novel tight junction modulating peptide for enhancing intranasal drug delivery

Recent progress in tight junction modulation for improving bioavailability

“…It was discovered in a directed screen for TJ-modulating peptides using a custom peptide library representing different physicochemical properties [101]. In stability studies, PN159 was shown to be chemically stable under conditions (pH 4.0 --7.3 and temperature 5 --25 C) relevant to the storage and application of intranasal products [102].…”

“…Different in vitro tissue studies were carried out with the PN159 permeation-enhancing additive [100,102,103]. The presence of PN159 showed significant improvement in epithelial permeability for the acetylcholinesterase inhibitor galantamine, a representative for small-molecule drugs, and for different therapeutic peptides, such as salmon calcitonin, human parathyroid hormone 1 --34 (PTH 1 --34 ) and human peptide YY 3 --36 (PYY 3 --36 ).…”

“…Intranasal administration [86] PN-159 Galantamine, salmon calcitonin, parathyroid hormone 1 --34 (PTH 1 --34 ), peptide YY3 --36 (PYY 3 --36 ), MC-4RA EpiAirwayÔ * Intranasal administration [100,102,103] Human peptide YY 3 --36 (PYY 3 --36 ) Rabbit Intranasal administration [102] Insulin Human Clinical Phase II; intranasal administration [104,105] Peptide YY 3 --36 (PYY 3 --36 ) Human Clinical Phase II; intranasal administration application, AT1002 was also shown to be valuable as an intratracheal (salmon calcitonin) [85] and a transdermal permeation enhancer [96]. In combination with the Tat protein, the epidermal permeation of small interfering RNA was significantly increased, which could provide a new therapeutic option in the dermal treatment of skin diseases (e.g., atopic dermatitis) [96].…”

Formulations for delivery of therapeutic proteins

“…Another tight junction modulation peptide was shown to provide a dramatic improvement in a drug permeation across epithelial tissue of salmon calcitonin, parathyroid hormone 1-34 (PTH 1-34 ), and peptide YY 3-36 (PYY 3-36 ). In addition, when the formulation containing this tight junction modulating peptide was dosed intranasally in rabbits, a dramatic increase in bioavailability was seen (Chen et al 2006). From a protein delivery perspective, it needs to be noticed, however, that the opening of tight junctions to modulate a paracellular transport has only been demonstrated for relatively small proteins and peptides, with an indication that 20 KDa may be the largest molecular weight protein that can be sufficiently delivered applying permeability enhancement approach (Miyamoto et al 2001).…”

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“…75 The animal models using sheep 76 , rat 77,78 , rabbit 79,80 , dog 81 and monkey 82 are reported for estimation of nasal absorption. Various studies have reported the usage of ex vivo nasal perfusion models (using sheep and rat).…”