Topical
Administration of Verapamil in Poly(ethylene
glycol)-Modified Liposomes for Enhanced Sinonasal Tissue Residence
in Chronic Rhinosinusitis: Ex Vivo and In
Vivo Evaluations
posted on 2023-02-06, 12:03authored byMaie S. Taha, Shallu Kutlehria, Anisha D’Souza, Benjamin S. Bleier, Mansoor M. Amiji
Verapamil is a calcium channel blocker that holds promise
for the
therapy of chronic rhinosinusitis (CRS) with and without nasal polyps.
The verapamil-induced side effects limit its tolerated dose via the
oral route, underscoring the usefulness of localized intranasal administration.
However, the challenge to intranasal administration is mucociliary
clearance, which diminishes localized dose availability. To overcome
this challenge, verapamil was loaded into a mucoadhesive cationic
poly(ethylene glycol)-modified (PEGylated) liposomal carrier. Organotypic
nasal explants were exposed to verapamil liposomes under flow conditions
to mimic mucociliary clearance. The liposomes resulted in significantly
higher tissue residence compared with the free verapamil control.
These findings were further confirmed in vivo in C57BL/6 mice following
intranasal administration. Liposomes significantly increased the accumulation
of verapamil in nasal tissues compared with the control group. The
developed tissue-retentive verapamil liposomal formulation is considered
a promising intranasal delivery system for CRS therapy.