Request Copyright Permission

A Quantitative Framework for Modulating Mucus Viscoelasticity to Extend Nasal Residence of Antiviral Proteins

Brunaugh AD, Xia G, Markovitz D.

Respiratory Drug Delivery 2026. Volume 1, 2026: 13-0.

Abstract:

Respiratory viruses exploit the upper airway as an early site of entry, yet therapeutic proteins delivered to this surface are rapidly removed by mucociliary clearance. We therefore examined whether nasal residence could be prolonged by treating mucus modulation as a viscoelastic design problem rather than a simple thickening or mucoadhesion problem. Using hydroxypropyl methylcellulose (HPMC) formulations, three linked properties relevant to this framework were evaluated: bench-scale mucus engagement, thermogelation behavior, and in vivo intranasal retention of AF647-labeled H84T banana lectin, a protein under investigation as a novel anti-viral.

Across these studies, formulation performance was consistently non-monotonic with respect to polymer concentration. Mucoadhesion peaked at 0.75% HPMC, whereas in vivo retention was greatest at 0.5% HPMC, indicating that adhesive force alone did not predict residence behavior. Sodium citrate strongly lowered the gelation temperature of 1% HPMC, but the response was steep and formulation-dependent, highlighting the need for careful tuning. In vivo, 0.5% HPMC prolonged intranasal retention relative to both PBS and 1% HPMC, supporting the existence of an intermediate operating window in which mucus interaction and clearance dynamics combine productively. Together, these findings argue that nasal protein delivery is best approached as a quantitativ iscoelastic design problem and provide a basis for further optimization of residence-extending formulations.