Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
Chemistry Department, University of Bari "Aldo Moro", via Orabona, 4, Bari 70125, Italy.
Eur J Pharm Biopharm. 2021 Oct;167:189-200. doi: 10.1016/j.ejpb.2021.07.015. Epub 2021 Jul 29.
Both dopamine (DA) loaded Solid Lipid Nanoparticles (SLN) and liposomes (Lip), designed for intranasal administration of the neurotransmitter as an innovative Parkinson disease treatment, were already characterized in vitro in some extent by us (Trapani et al., 2018a and Cometa et al., 2020, respectively). Herein, to gain insight into the structure of SLN, X-ray Photoelectron Spectroscopy Analysis was carried out and DA-SLN (SLN 1) were found to exhibit high amounts of the neurotransmitter on the surface, whereas the external side of Glycol Chitosan (GCS) containing SLN (SLN 2) possessed only few amounts. However, SLN 2 were characterized by the highest encapsulation DA efficiency (i.e., 81%). Furthermore, in view of intranasal administration, mucoadhesion tests in vitro were also conducted for SLN and Lip formulations, evidencing high muchoadesive effect exerted by SLN 2. Concerning ex-vivo studies, SLN and Lip were found to be safe for Olfactory Ensheathing Cells and fluorescent SLN 2 were taken up in a dose-dependent manner reaching the 100% of positive cells, while Lip 2 (chitosan-glutathione-coated) were internalised by 70% OECs with six-times more lipid concentration. Hence, SLN 2 formulation containing DA and GCS may constitute interesting formulations for further studies and promising dosage form for non-invasive nose-to-brain neurotransmitter delivery.
我们已经在一定程度上对用于经鼻腔给予神经递质的创新帕金森病治疗的载多巴胺(DA)固体脂质纳米粒(SLN)和脂质体(Lip)进行了体外特性研究(Trapani 等人,2018a 和 Cometa 等人,2020 年)。在此,为了深入了解 SLN 的结构,我们进行了 X 射线光电子能谱分析,发现 DA-SLN(SLN1)在表面上具有大量的神经递质,而含有甘醇壳聚糖(GCS)的 SLN(SLN2)的外表面则只含有少量的神经递质。然而,SLN2 的包封 DA 效率最高(即 81%)。此外,鉴于经鼻腔给予,我们还对 SLN 和 Lip 制剂进行了体外粘膜粘附试验,证明了 SLN2 具有很强的粘膜粘附效果。关于离体研究,发现 SLN 和 Lip 对嗅鞘细胞是安全的,荧光 SLN2 以剂量依赖的方式被摄取,达到 100%的阳性细胞,而载有壳聚糖-谷胱甘肽的 Lip2(Lip2)则被 70%的嗅鞘细胞内化,脂质浓度增加了六倍。因此,载有 DA 和 GCS 的 SLN2 制剂可能是进一步研究的有趣制剂,也是非侵入性鼻脑递药的有前途的剂型。