Intranasal lipid nanocarriers: Uptake studies with fluorescently labeled formulations

Abstract

Drug delivery by the intranasal route allows both systemic absorption and non-invasive brain targeting, due to the unique connection provided by the olfactory and trigeminal nerves between the brain and the external environment. Lipid nanocarriers can improve intranasal drug delivery by enhancing bioadhesion to nasal mucosa, and by protecting the encapsulated drug from biological degradation and transport efflux proteins. In this study two different biocompatible lipid nanocarriers were compared: nanoemulsions and solid lipid nanoparticles. The nasal uptake was investigated by labeling the nanocarriers lipid matrix with two fluorescent probes, 6-coumarin and rhodamine B, both lipophilic, yet characterized by different water solubility, in order to mimic the behavior of hypothetic drug compounds. Ex vivo permeation, in vivo pharmacokinetics and biodistribution studies were performed. 6-coumarin, water insoluble and therefore integral with the lipid matrix, was taken up to a limited extent, within a long timeframe, but with a proportionally more pronounced brain accumulation. In nanoemulsions soluble rhodamine B showed a relevant systemic uptake, with good bioavailability, likely due to the prompt release of the probe at the nasal mucosa.