Muntoni Elisabetta, Marini Elisabetta, Ferraris Chiara, Garelli Sara, Capucchio Maria Teresa, Colombino Elena, Panciani Pier Paolo, Battaglia Luigi
Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, 10125 Turin, Italy.
Department of Veterinary Sciences, University of Turin, Largo Paolo Braccini 2, Turin, 10195 Grugliasco, Italy.
Colloids Surf B Biointerfaces. 2022 Jun;214:112470. doi: 10.1016/j.colsurfb.2022.112470. Epub 2022 Mar 23.
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.
由于大脑与外部环境之间通过嗅觉神经和三叉神经建立的独特联系，经鼻途径给药既可以实现全身吸收，也能够实现无创性脑靶向给药。脂质纳米载体可以通过增强对鼻黏膜的生物黏附性，以及保护被包裹的药物免受生物降解和转运外排蛋白的影响，来改善经鼻给药。在本研究中，对两种不同的生物相容性脂质纳米载体进行了比较：纳米乳剂和固体脂质纳米粒。通过用两种荧光探针6-香豆素和罗丹明B对纳米载体脂质基质进行标记来研究鼻腔摄取情况，这两种探针均具有亲脂性，但具有不同的水溶性，以便模拟假设药物化合物的行为。进行了体外渗透、体内药代动力学和生物分布研究。6-香豆素不溶于水，因此与脂质基质结合，在较长时间内摄取程度有限，但脑内蓄积相对更明显。在纳米乳剂中，可溶的罗丹明B显示出显著的全身摄取，具有良好的生物利用度，这可能是由于探针在鼻黏膜处迅速释放所致。
