Separation Engineering of Chinese Traditional Medicine Compound, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
Department of Pharmaceutical Analysis, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People's Republic of China.
Drug Deliv Transl Res. 2018 Feb;8(1):83-96. doi: 10.1007/s13346-017-0438-8.
Alpha-asarone is a bioactive component of Acorus tatarincuii Schott with low bioavailability, which is often used for treatments of various brain diseases in clinical setting. This study was to formulate biodegradable methoxy polyethylene glycol-polylactic acid (mPEG-PLA) nanoparticles (NPs) surface-modified by lactoferrin (Lf), for delivering α-asarone into the brain following intranasal administration. Alpha-asarone NPs were prepared by premix membrane emulsification. The relative parameters were optimized by a Box-Behnken experimental design. The particle size, zeta potential, and dispersibility index of NPs and Lf-NPs were characterized. Their ex vivo permeation, pharmacokinetics, distribution in the brain and other tissue, brain targeting, and toxicity were investigated. Following intranasal administration, Lf-NPs had a better permeability and no significant poor bioavailability compared to NPs; the area under curve from 0 to 12 h of α-asarone in Lf-NPs of the olfactory bulb, hippocampus, olfactory bundles, and thalamus were 2.14-, 4.17-, 3.62-, and 1.96-fold of those in NP group, respectively. Lactoferrin could enhance the efficacy of brain targeting with NPs and reduce its liver accumulation. Toxicity of NPs on nasal mucosal cilia and epithelial cells was also decreased by Lf. To summarize, these results demonstrate that Lf-NPs of α-asarone have potential as a carrier for nose-to-brain delivery of α-asarone for brain diseases.
α-细辛脑是菖蒲的一种生物活性成分，生物利用度低，常用于临床治疗各种脑部疾病。本研究旨在通过表面修饰乳铁蛋白（Lf），制备可生物降解的甲氧基聚乙二醇-聚乳酸（mPEG-PLA）纳米粒（NPs），用于经鼻给药后将 α-细辛脑递送至脑部。采用预混膜乳化法制备 α-细辛脑 NPs，采用 Box-Behnken 实验设计优化相对参数。对 NPs 和 Lf-NPs 的粒径、Zeta 电位和分散指数进行了表征。考察了它们的体外渗透、药代动力学、在脑及其他组织中的分布、脑靶向性和毒性。经鼻给药后，Lf-NPs 与 NPs 相比具有更好的渗透性，没有明显的生物利用度降低；Lf-NPs 组嗅球、海马、嗅束和丘脑的 α-细辛脑的 AUC0-12h 分别为 NP 组的 2.14、4.17、3.62 和 1.96 倍。Lf 可增强 NPs 的脑靶向作用，并减少其在肝脏中的蓄积。Lf 还降低了 NPs 对鼻黏膜纤毛和上皮细胞的毒性。综上所述，这些结果表明，Lf-NPs 载 α-细辛脑具有作为治疗脑部疾病的经鼻递药载体的潜力。
