Summary
Childhood absence epilepsy (CAE) necessitates for efficient treatment due to long term effects of the disease’s comorbidities and treatments’ side effects. The majority of patients are treated with oral antiseizure drugs. However, drug delivery to the brain can be challenging because of the selectivity of the blood-brain barrier (BBB). To circumvent the BBB, a non-invasive administration route is desired, as it allows for pain-free application without the need for a healthcare professional. One option is nose-to-brain delivery of nanoparticles. This approach has the advantage of reducing the administered drug dose to children by its efficient, targeted delivery. Lamotrigine was used in this study, as it is a well-established antiseizure drug in CAE. Nanostructured lipid carriers (NLC) were selected as carrier system due to their biocompatibility and straight-forward production. NLC incorporate a liquid lipid into a matrix of solid lipids which melt above body temperature. This reduces the crystallinity of the matrix and allows for a higher and more stable drug load compared with particles made from solid lipids only. Quality target product profiles were determined following a quality-by-design approach, and the influencing factors were identified using an Ishikawa diagram. A Design of Experiments approach was applied to define the design space for the composition and production of NLC. The optimised formulation was characterised physiochemically and in vivo. An absence epilepsy rat model (GAERS) demonstrated a reduction in the time spent in seizures during hours 3-6 following intranasal administration of 28 µg encapsulated lamotrigine per rat.