Cribriform plate
Nasal epithelium

INTRAVAIL®—
Transmucosal Absorption Enhancement Technology

Intravail® is a synthetic compound intended for use as an absorption enhancement agent for nasal formulations of therapeutic agents.

Intravail®

Intravail® is a patented trans-mucosal delivery enhancement agents that has overcome the principal limitations of many of the previously explored absorption enhancers, namely, poor bioavailability and damage to the nasal mucosa. Intravail® is now finding application in a number of clinical indications in the CNS and endocrine areas.

Effect of Intravail® Enhancer on Insulin Permeation

Fluorescence Microscopy, vertical sections of rat nasal mucosa showing penetration of FITC-labeled insulin, 0.125% Intravail, 10 min. after instillation

Without Intravail® Enhancer
With Intravail® Enhancer

Rat Nasal Epithelium, Magnification 40X

It is likely that the Intravail® enhance drug passage across mucosal membranes by both enhancing transcellular and paracellular mechanisms across the nasal epithelium.

The virtually complete lack of insulin absorption upon intranasal administration in the diabetic primate model as confirmed by the lack of adsorption of RTC-labeled insulin in the absence of Intravail®, as seen in these fluorescence light micrographs of vertical cross-sections of nasal septa excised from rates treated with RTC insulin. RTC: Fluorescein isothiocyanate.

Transmucosal Absorption Enhancement

Reduction in TEER
Bioavailability
Molecule size
Sumatriptan

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Safety

  • Odorless, tasteless, non-toxic, non-mutagenic and non-irritating to mucosal membranes
  • Delivery of potent peptide, protein, and large molecule drugs
  • No alteration of the chemical form or biological integrity of the drug – i.e., no liposomes particles, pumps, patches or emulsions
  • Rapid drug absorption and onset of action
  • Controlled transient permeation of the nasal mucosal barrier
TAP TO CONTINUE
Intravail
Olfactory Transport
Transmucosal Absorption
Safety
References:Maggio ET et al. Drug Deliv and Transl Res. 2013;3:16-25
References:Maggio ET et al. Drug Deliv and Transl Res. 2013;3:16-25
References:Maggio ET. Expert Opin Drug Dev 2006;3:529-539
References:Neurelis, Inc. Delivering Innovative Approaches. Available at: https://www.neurelis.com/our-technologies. Accessed December 05, 2019.
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Intravail® Demonstrates Absorption Enhancement Properties: Reduction in TEER

    Transepithelial electrical resistance (TEER) measurement is used to assess the barrier function of epithelial cells on these porous supports. Reduction in TEER as an indication of paracellular absorption using normal human tracheal/bronchial epithelial cell-derived mucociliary tissue.

    Chen S et al. Histochem Cell Biol. 2015;144:509-515. Maggio ET et al. Drug Deliv and Transl Res. 2013;3:16-25.

    Demonstrated Increased Bioavailability

    • Comparable in efficiency to subcutaneous injection via the intranasal administration route

    ZT-031 with Intravail® pharmacokinetics studies showing good systemic exposures was achieved with dose related increases in maximum plasma concentration. Similar findings were observed in rats and rabbits.

    Eddy P et al. Poster presentation. ASBMR 30th Annual Meeting, Montreal, Quebec, Canada 2008.

    Molecule Size—Calcitonin, Insulin, Leptin, HGH and EPO

    • Delivery of potent peptide, protein, and large molecule drugs that can currently only be delivered by injection
    • Nasal delivery of large molecules with Intravail® achieves high bioavailability when compared to IV/sub-Q formulations
    • Opens up new route of administration for entire class of therapeutics with IV/SC delivery

    Maggio ET et al. Drug Deliv and Transl Res. 2013;3:16-25

    Intranasal Sumatriptan Plasma Profile

    • Small molecules, therapeutic proteins, peptides, non-peptide macromolecules (up to ~ 30KDa)
    • 20mg nasal spray: Achieves therapeutic blood levels 30X to 60X faster than Imitrex (2 min. vs. 60-120 min)
    • Relative B/A ~90% compared to tablet
    • Tmax reduced from 60 minutes down to 8 minutes

    Data on file, Neurelis, Inc.