Topical Administration of Verapamil in Poly(ethylene glycol)-Modified Liposomes for Enhanced Sinonasal Tissue Residence in Chronic Rhinosinusitis: Ex Vivo and In Vivo Evaluations.

Abstract

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.