Dehydration affects drug transport over nasal mucosa

Abstract

Formulations for nasal drug delivery often rely on water sorption to adhere to the mucosa, which also causes a higher water gradient over the tissue and subsequent dehydration. The primary aim of this study was therefore to evaluate mucosal response to dehydration and resolve the hypothesis that mucoadhesion achieved through water sorption could also be a constraint for drug absorption via the nasal route. The effect of altering water activity of the vehicle on Xylometazoline HCl and 51 Cr-EDTA uptake was studied separately ex vivo using flow through diffusion cells and excised porcine mucosa. We have shown that a modest increase in the water gradient over mucosa induces a substantial decrease in drug uptake for both Xylometazoline HCl and 51 Cr-EDTA. A similar result was obtained when comparing two different vehicles on the market; Nasoferm ® (Nordic Drugs, Sweden) and BLOX4 ® (Bioglan, Sweden). Mucoadhesion based on water sorption can slow down drug uptake in the nasal cavity. However, a clinical study is required to determine whether prolonged duration of the vehicle in situ or preventing dehydration of the mucosa is the most important factor for improving bioavailability.

Preparation and Evaluation of 6-Maleimidohexanoic Acid Grafted Chitosan Nanoparticles as a Novel Carrier for Intranasal Protein Delivery

“…Ex vivo permeability. Permeation study was performed by Franz diffusion cells [7]. Phosphatebuffered saline (PBS) pH 7.…”

Excipients Used for Modified Nasal Drug Delivery: A Mini-Review of the Recent Advances

“…The nasal route of administration is used for treating local inflammation, allergic and common rhinitis, and nasal congestion. The active compounds that are commonly used against these diseases are antihistamines, glucocorticoids, or decongestants in the form of nasal spray, drops, solutions, gels, or powders and other types of formulations, including emulsions, suspensions, and microparticles [ 6 , 25 ]. The nasal route is used for either local or systemic action.…”

“…In addition, there is a restriction regarding the absorption of the poorly water-soluble drugs due to the low volume of the nasal cavity, which reduces the administered amount to 100–150 μL [ 28 ]. The permeability also decreases for the polar and large molecules and for peptides and proteins [ 25 ]. However, by using the correct excipients, including bioadhesive polymers, enhancers, and enzymatic inhibitors, the drug permeability and residency in the nasal cavity can be improved [ 29 ].…”

“…The mucus can also decrease the drug absorption by binding the drug to mucin, which is the primary protein of the mucus. While the small moieties can pass through easily, the charged or larger units can be caught in the mucus gel [ 25 ]. Mucus also contains different enzymes which can influence the stability of protein- and peptide-based drugs; proteases degrade peptides and proteins by attacking them.…”

Stability Study of Mucoadhesive Microsphere Containing Nateglinide by Using Biodegradable Polymer Chitosan

“…Over the last few decades, the application of mucoadhesive polymers in nasal drug delivery systems has gained interest among pharmaceutical scientists as a means of promoting dosage from residence time in the nasal cavity as well as for improving intimacy of contact with absorptive membranes of the biological system. In addition, the enhanced paracellular absorption following the swelling of the mucoadhesive polymers on the nasal membranes provides an important way for the absorption of the macromolecules through the nasal cavity [1,2]. Nasal drug delivery can also provide a route of entry to the brain that circumvents the blood-brain barrier because the olfactory receptor cells are in direct contact with the central nervous system.…”