Fenfluramine nanoparticles for nasal administration

GERPAC Congress highlights

The successful development of fenfluramine-loaded albumin nanoparticles paves the way for nasal administration of fenfluramine in drug-resistant epilepsy in children. Nasal administration would deliver the drug to the brain via the olfactory and trigeminal nerves and avoid significant hepatic metabolism to norfenfluramine which is cardiotoxic, explained Maxime Petit.

Successful nasal delivery of a drug depends on having a small volume and a prolonged residence time in the nasal cavity, to overcome mucociliary clearance. This calls for a formulation that combines a high concentration of the drug and a gelling agent or muco-adhesive.

In this study fenfluramine-loaded albumin nanoparticles were prepared and dispersed in an aqueous solution of pectin to make a final drug concentration of 10mg/mL. The particles were 107-135nm making them small enough to pass through the nasal mucosa. A stability study showed that 18.6% of the fenfluramine was released after three hours, indicating that the majority of the drug remained encapsulated. Local cytotoxicity (cell lysis) was assessed by measuring lactate dehydrogenase (LDH) release from a suitable cell line, as a model for nasal epithelium. The results showed that fenfluramine alone caused extensive cell lysis whereas with the nanoparticle formulation it was negligible.

The authors concluded that the sizes of the nanoparticles and the concentration of fenfluramine made the nanoparticle formulation suitable for therapeutic use. They plan to complete physicochemical studies before starting in vivo studies in mice.

Petit M et al. Development of fenfluramine in albumin nanoparticles for nasal administration. Short communication. GERPAC Congress 2025

Photo – Maxime Petit