Electrospun mucoadhesive nanofibrous films for intranasal delivery of propranolol hydrochloride for migraine prophylaxis

Abstract

Migraine treatment failure is often associated with the delayed onset and variable efficacy of conventional oral medications, which are further limited by poor patient compliance due to gastrointestinal side effects and frequent dosing requirements. To address these challenges, a fast-disintegrating mucoadhesive nanofibrous film was developed for the intranasal administration of propranolol hydrochloride (PROP), a well-established migraine prophylactic agent. The electrospun films were formulated using rapidly dissolving pullulan and chitosan, known for its strong mucoadhesive properties, ensuring immediate drug availability at the site of action and promoting permeation through the nasal epithelium via the nose-to-brain delivery route, thereby bypassing first-pass metabolism. The films demonstrated sufficient elasticity, allowing them to be cut and rolled into solid dosage forms for convenient intranasal administration. Upon hydration, the films transitioned into a gel-like state, as confirmed by rheological studies conducted in simulated nasal electrolyte solution (SNES) at 35 °C. In vitro release studies in SNES revealed rapid PROP dissolution, while cytocompatibility was assessed using the Calu-3 cell line, showing dose-dependent effects likely influenced by the PROP concentration. Mucoadhesion studies indicated a significant enhancement of retention at the nasal mucosa, with higher chitosan concentrations contributing to improved drug residence and facilitated transport across the epithelium. To overcome the limitations of oral PROP administration, such as poor bioavailability and delayed onset of action, the proposed electrospun nanofiber films might offer a promising alternative for effective and patient-friendly migraine therapy via intranasal delivery.